Pharmacology Text Book

PHARMACOLOGY
YEHIA HASSAN MOHAMED ELMALIK

pharmacology
Course content:
 General pharmacological principles
 Drugs acting on the autonomic nervous system
 Autacoids
 Central nervous system
 Drugs used for respiratory tract disorders
 Hormones and antagonists
 Analgesics, Antipyretics and Anti-inflammatory agents
 Drugs affecting renal and cardiovascular functions
 Drugs acting on the Blood and Blood Forming Agents
 Drugs used in Gastro-Intestinal diseases
 Chemotherapy of Parasitic Infections
 Chemotherapy of Microbial diseases
 Antineoplastics and Immunosuppressants
 Vitamins
 Locally Acting Drugs
DR. yahia Hassan Mohamed Elmalik PhD Page 2

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Unit 1
Essential Principles of
Pharmacology

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INTERODUCTION
Pharmacology: The study of biochemical and physiologic aspects of drug
effects, including absorption, distribution, metabolism, elimination, toxicity,
and specific mechanisms of dug action.
Drug: may be defined as any substance or mixture of substances designed

for administration to man or other animal for use in the diagnosis, treatment,
investigation or prevention of disease or for the modification of
physiological function.
To be of therapeutic use a drug must produce the required effect for the
required length of time, which implies an adequate concentration of drug at
the site of action, there fore many fact ors which effect the concentration or
activity of a drug at the target site. These include the extent and rate of
absorption, plasma or tissue binding, the rate of biotransformation and
excretion; and the activity of metabolites, these processes occur
simultaneously and the concentration of a drug in the body at any one time,
and so the duration and intensity of its effects depend on the relative balance
of these factors.
A. Drug classification
Drugs are organized in taxonomies (classifications) in three ways.
1. Chemical classification, drugs are according to their
classified structure.
2. Pharmacologic classification drugs are classified
according to physiologic activities and mechanisms of
action.
3. Therapeutic classification, drugs are classified according
to therapeutic indications.
B. Drug legislation
1. Official standards for drugs were established in the
United States with the Pure Food and Drug Act of 1906
and outlined in the United States Pharmacopoeia (USP)

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and the National Formulary (NF). Federal laws
pertaining to medication administration are discussed
below.
2. Narcotics were addressed by the Harrison Narcotic Act
of 1914, which regulated the manufacture, importation,
sale, and use of opium, cocaine, marijuana, and certain
drugs defined as narcotics.
3. The Federal Good, Drug, and Cosmetic Act of 1938
mandated that data on the safety of a new drug be
brought to the U.S. Food and Drug Administration
(FDA) before the product could be marketed.
4. Prescription and nonprescription drugs were
distinguished in the Durham-Humphrey Amendment of
1952.
5. The safety and effectiveness of drugs, effective and
therapeutic claims, and drug development and
manufacturer were covered in the Kefauver Harris
Amendment of 1962.
6. Drug abuse and dependence were addressed in the
Comprehensive Drug Abuse Prevention and Control Act
1970, which regulated the distribution of narcotics and
created the schedule of controlled substances.
7. States, localities, and institutions also regulate drugs.
These laws and policies must be compatible with federal
laws; they may not refute federal restrictions but may
Impose additional ones.

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C. Controlled substances
1. Controlled substances were first defined under the
Harrison Narcotics Act 1914 described above.
2. Subsequent laws, chiefly the Comprehensive Drug Abuse
Prevention and Control Act of 1970, categorized these
drugs into schedules according to usefulness and
potential for abuse.
D. Official standards
1. Because the properties of drugs (e.g., purity potency,
bioavailability, efficacy, and safety/toxicity) can vary,
standards have been established and are enforced by the
government.
2. Standards outlined in USP and NF provides a method for
measuring the attribute to be evaluated and the
acceptable level or range for measurements.
3. The properties of drugs are summarized as follows:
a. Purity – Completely pure drugs are rarely
attainable. Pure drugs contain only one chemical
agent, but additives may be needed to facilitate
formulation or manipulate absorption.
Environmental and extraneous substances may be
present in certain quantities and types.
b. Potency- The drug's potency, or strength, depends
on the concentration of active drug in the
medicinal preparation.
c. Bioavailability- The drug's bioavailability is a
measure of the rate and extent of drug transfer
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from its administration site of the systemic
circulation.
d. Efficacy- A drug's efficacy is its effectiveness in
promotion desirable clinical changes. Objective
measures are rarely available, and data are
interpreted subjectively. Efficacy of therapeutics
is rated by the National Research Council of the
National Academy of Science for the FDA using
the following scale:
1. Ineffective – no substantial evidence of
effectiveness
2. Ineffective as a fixed combination – not
effective in fixed dosage combinations
for reason of safety or because one or
more components lack substantial
evidence of effectiveness.
3. Possibly effective- effectiveness might
be shown eventually, but at the present
time shows little evidence of
effectiveness.
4. Probably effective- some evidence of
effectiveness, but insufficient to establish
drug effectiveness.
5. Effective- substantial evidence of
effectiveness.

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6. Effective but- effective with qualification
or restriction until completion of further
studies.
e. Safety/ toxicity:
(1) All chemicals are toxic to some degree.
(2) The safety of a drug is measured by the incidence and
severity of adverse reactions.
(3) Safety is determined by the degree between therapeutic and
toxic dosages.
(4) Complete safety cannot be determined regardless of testing
Before release of a drug.

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E. Drug names
1. The chemical name is the chemical structure of the
compound.
2. The generic name, used worldwide as established
through the Committee on International Nonproprietary.
Names of the World Health Organization, is the name
selected by the original manufacturer of the drug based
on the chemical structure. It is also known as the
nonproprietary name because it is not restricted by the
trademark.
3. The trade name or brand name is a proprietary name
owned by the company that manufactures of the drug. It
is registered as trade mark.
4. For example, acetaminophen is the genetic name for the
drug most commonly referred to by its brand name
Tylenol.
F. Drugs sources
1. Drugs are derived from many sources, principally plants,
animals, and minerals.
2. Most modern drugs are synthetic chemical compounds
manufactured in laboratories.
3. Some are semi synthetic drugs that are chemically altered
(e.g., levorphanol).
4. Other drugs are genetically altered or engineered; this
group of drugs is growing in importance as source of
drugs today (e.g., Humulin, epoetin [Epogen]).
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II- Classification of pharmacology.
A. Pharmacodynamic (actions):-
1. This is the process by which drugs influence the cell
physiology to achieve the desire result.
2. Drugs can inhibit or active ate a process pr replace a
missing element.
3. All but a small number of drugs interact with specific
sites called receptors.
4. Receptors are cellular proteins or nucleic acids that
regulate the physiological and metabolic activities of the
cell in either of two ways.
a. Agonists (activators) bind to the receptor on the cell membrane
and act on the cell through the receptor to produce a
pharmacologic effect.
b. Antagonists (blockers) bind to the receptor and prevent the cell
from producing an effect. Antagonists may also block the action
of another drug.
5. The dose-response curve is the relationship that exists
between the drug and biologic effect in the process. The
response increases as drug concentration increases.
6. Potency is the drug activity measured in terms of the
dose required to produce a particular effect. A drug with
high degree of effect at a low dose is more potent that a
drug with a low activity at a high dose.
7. Efficiency is the maximal effect produced by a drug.
This is important to know when deciding between two
drugs that have similar actions. For example, two
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antibiotics may effectively kill the same organism, but
one may take many more doses than another, making the
other more effective.
B. Pharmacotherapeutics (indications):-
1. The desired effect is the intended effect or the reason the
drug is administered to a particular client at a given time.
2. At times the drug needed has toxic side effects, and the
benefits must outweigh the risks to determine if the drug
should be administered.
3. The intended effect of the drug prescribed must be
appropriate for the client and the illness.
C. Pharmacokinetics
1. Pharmacokinetics is the process by which the body
absorbs the drug into the bloodstream, distributes it to its
site of action, to other body compartments metabolizes it,
and excretes it. The therapeutic action of the drug
depends on its pharmacokinetic properties.
2. Onset of action is the time it the drug takes for the drug
to reach its minimum effective concentration.
3. Peak effect occurs when the drug is exerting its
maximum effect and it is attained at its highest
concentration.
4. Duration of action is the length of time that the drug
remains above its minimum effective concentration.
5. Absorption involves the transfer of the drug across
biologic membranes to the blood. A biologic membrane
may be the skin, mucous membranes of the eye or ear,
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vagina or rectum, stomach or intestinal lining, or
subcutaneous (SC) or muscle tissue. Biologic
membranes also exist inside the body cavities and drugs
are sometimes given directly into them (e.g.,
intraperitoneal or intrathecal administration).
a. With oral medications, absorption occurs from the
GI tract by diffusion across the mucosal barrier.
The quantity and rate of absorption are influenced
by a number of factors (Display 1-2).
Factors that influence absorption of oral medications
 Presence or absence of food
 Solubility of the drug
 Stability of the drug in gastric pH
 Dosage from (eg, capsule, tablet, extended release)
 Length of time in the stomach
 Presence of other drugs
 Circulation in the gut
 Alteration of gastric pH (eg, as seen in client's
receiving H2-blockers or proton pump inhibitors)
 Pathology (eg. diseases that increase or decrease
peristalsis, change gastric emptying, or reduce the
surface area (as it is the case in surgical removal of
part of the stomach or intestine).
b. With parenteral medications, the absorption rate is

more rapid and predictable because IV
administration places the drug directly in the
plasma. With other parenteral sites (intramuscular,
IM and SC), the circulatory system has more rapid
access to the site of administration. Factors
affecting absorption of parenteral medication
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include solubility of the drug in the interstitial
tissue, the area of the absorption of capillary
membrane, and muscle mass and circulation in the
area.
c. The slowest from of absorption is thought the skin
and mucous membranes.
6. Bioavailability is the extent to which a drug is absorbed
in the active form and transported to blood.
7. Distribution is the process by which drugs, and is
transported by blood or other body fluids and tissues and
to the site of action. It depends on the plasma protein
binding, lipid solubility of the drug, and circulation of the
patient.
a. Protein binding means that a percentage of the drug has bound
to the plasma proteins, leaving only the amount of free drug in
the circulation tobe distributed to produce eventually the drug
action. This makes protein binding an important aspect of
drug distribution. For example, if a drug is 50% protein bound
and the dose given is 100 mg, only 50 mg is available to exert
its therapeutic effect.
b. Lipid solubility is important because the cell membrane has a
concentration of lipids; therefore, if the drug is lipid soluble, it
can pass through the cell membrane to exert its action.
c. The amount of drug present in the tissues helps determine how
effective the drug will be.
d. Initial distribution of the drug depends on cardiac output and
blood flow to local tissue.
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e. Drug concentration at specific sites depends on the density of
blood vessels in tissue, the local vasodilatation or constriction,
and rate of blood circulation. Certain drugs tend to
concentrate in specific tissues. E.g. adipose tissue, fats liver
f. The placental barrier and blood-brain barrier are the body's
defense mechanisms. Some drugs pass through these barriers,
whereas others do not.
9. Biotransformation: many drugs are lipid soluble or
weak organic acids or bases and, though they will pass
across the glomeruli into the renal tubules, they are
readily reabsorbed by diffusion through the renal tubular
cells. To be excreted these drugs must be changed to
more ionized and less lipid soluble compounds. these be
non – synthetic reactions such as oxidations , reductions
or hydrolysis (phase 1 Metabolism ) which introduce or
unmask functional group for a second , and synthetic
phase(phase 2 metabolism in which the drug or its
metabolites is conjugated with endogenous molecules
such as glucouronic acid , sulphates acetyl groups ,
methyl groups or emino acids . this masks the active
groups , makes he compound more polar and less lipid
soluble , and so facilitates excretion .
The liver is the major site of metabolism for many drugs, but many
non hepatic organs such as the lungs, kidneys and gastrointertinal
tract.
Drug metabolism has at least 4 consequences:
(1) Conversion of a pharmacologically active to inactive (most drugs).
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(2) Conversion of a pharmacologically active to inactive e. g.
Active drugs active metabolite

Phenylbutezone oxyphenbutazone
Propranolol 4- hudroxy propranotoi
Codeine morphine
(3) Conversion of a pharmacologically inactive to an active
substance e.g.
In active drug active Metabolite
Talampicellin ampicillin
Benorylate paracetamol and
(4) forming a toxic metalsolite from an initially less toxic drug e. g.
Phenacetin could be transformed into an aniline derivative which causes
methemoglobinemis.
.
Routes of Administration
1- Oral Route
The oral route is the most economical and most convenient way to give
medications which are given by mouth in either solid form, as a tablet
or capsule, or in liquid form, as solution or syrup. Once the medication
enters the mouth, it must be swallowed to reach the stomach. Then it
must pass to the point of absorption, most commonly the small
intestine, although some medications are absorbed in the stomach.
This process takes time and is affected by several factors including the
presence of food (which slows the process) or digestive disorders. It is
important to refer to a reliable drug reference guide to determine if the

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medication should be given with or without food and whether any
specific assessments should be done before dispensing it.
2- Sublingual (under the tongue) and buccal (between the cheek and
gum) routes of administration are used when a rapid action is desired,
or when a drug is specifically designed to be easily absorbed into blood
vessels. The medication enters the blood stream directly from the
richly vascularized mucous membrane of the mouth and produces its
effects more quickly than drugs that are swallowed. The drug form
cannot obtain the same effect if swallowed than if sublingually
administered.
When taking medication by the sublingual route, the patient should hold
the tablet under tongue until it is completely absorbed. For buccal
administration, the patient should place the tablet between the cheek
and gums, close the mouth, and hold the tablet there until it is absorbed.
It is important to remind the patient not to drink water or swallow
excessively until the tablet is completely absorbed.

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(Routes of administration)
Route Example
oral (by mouth) swallowed
sublingual (under the tongue)
buccal (dissolves in the cheek)
iv (vein)
parenteral (injection through veins, Intravenous

etc, intravenous for rapid entry of intraterial (artery)
the drug into the circulatory
intracardiac (heart)
system)
intraspinal/intrathecal(spinal fluid)
intrasynovial (joint-fluid area)
subcutaneous (beneath the skin)
intramuscular (muscle)
topical (applied to surface of skin transdermal (skin surface)

or mucous membranes)
conjunctival (conjunctiva)
intraocular (eye)
intranasal (nose)
aural(ear)
intrarespiratory(lung) or pulmonary
rectal (rectum)
vaginal (vagina)
urethral (urethra)

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Common Dosage Forms
Route Example
oral Tablets
capsules
solutions
syrups
elixirs
suspensions
magmas
gels
powders
touches/lozenges
parenteral solutions
ointments
topical
creams
pastes
powders
aerosols
lotions
transdermal patches
sprays
inhalants
suppositories
enemas
emulsions
sponges
3- Parenteral Routes
Medications that are injected directly into the tissues of the body do not
pass through the liver before entering the bloodstream. Avoiding this
"first pass effect" prevents medications from being inactivated in the
liver. Drugs may be injected into
 A muscle: intramuscular
 A vein: intravenous
 The skin: intradermal
 The tissue beneath the skin: subcutaneous

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 The spinal column (intrathecal)
Drugs such insulin is inactivated in digestive juices, so swallowing
them would be ineffective.
Parenteral routes also offer the potential for quick absorption of injected
medication into the bloodstream and rapid effect (especially for the
intravenous route). Disadvantages include pain during administration
and the possibility of infection since the skin is punctured. Also, once
the medication is injected, there is no way to retrieve it if an error has
been made.
4-Topical Routes
Topical medications are applied to the surface of the skin or mucous
membranes. The desired effect can be local or systemic. Other topical
routes are inhalation, ophthalmic, otic, nasal, and rectal.
Factors affecting the metabolism of drug.

The metabolism of a drug is influenced by many factors which account
in large part for the individual and species differences of the response.
These factors are genetic, physiological, phermacodynamic and
environmental.
(1). Genetic Factors:
A classic example is due to a genetically determined deficiency of
glucose – 6-phosphate dehydrogenase (G – 6 – PD ) in the red blood
cell when drugs such as primaquime , Pamaquine and P –
aminosalicylic acid cause an , oxidative denaturation of hemoglobin
and hemolytic .
Isonicontinic acid hydrazide (INAH) is inactivated by acetylation and
people are either slow or fast in activators due to a genetically

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determined level of enzyme slow in activators, due to the higher blood
level of isoniazide which can result, are more liable to get toxic effects.
These in clued mental disturbances and a peripheral neuropathy.
(2) Physiological factors:

Age may have a pronounced effect on the handling of drugs. The fetal
and new born animal has a limited capacity to metabolize drugs such as
chloramphenicol due to the immaturity of the liver microsomal system,
which in the human is not fully developed till eight weeks or age. The
elderly person may be similarly deficient in drug – handling.

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STUDY QUESTIONS
1. Safety of a drug is determined
by the degree between :
a. Therapeutic and toxic
doses.
b. Potency and efficacy.
c. Subtherapeutic and toxic
levels.
d. Side and adverse effects.
2. The name selected by the
original manufacturer based on
the chemical structure of the
drug is the :
a. Chemical name.
b. Generic name.
c. Trade name.
d. Drug name.
3. When a drug binds to a receptor
to produce a pharmacologic
effect , the drug may be called a
(n) :
a. Agonist.
b. Antagonist.
c. Blocker
d. Accelerator

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4. The interaction of one drug
increased by the presence of a
second drug is known as ;
a. Synergism
b. Additive effects
c. Antagonism
d. Potentiation
5. The extent to which a drug is
absorbed and transported to
target tissue is known as :
a. Steady – state
accumulation
b. Therapeutic drug
levels
c. Bioavailability
d. Distribution
6. When two drugs given together
have an effect equal to the sum
of their respective effects , the
interaction is known as :
a. Potentiated
b. Antagonized
c. Agonist
d. Additive
7. distribution is effected by :
a. biotransformation
b. excretion
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c. protein binding
d. lipid binding
8. Absorption, distribution, and
excretion may be increased by
which of the following
diseases?
a. Hyperthyroidism
b. Renal
insufficiency
c. Liver diseases
d. Hypothyroidism
9. an unexpected effect from a
drug is known as a(n) :
a. Side effect
b. Adverse effect
c. Toxic reaction
d. Allergic reaction
10. When a drug is 50% protein
bound , it means that :
a. 50% of the drug
destroys protein.
b. 50% of the dose is at
work.
c. 50% of the drug is
excreted in the kidneys.
d. Protein must be
restricted in the diet.
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Unit II
Drugs acting on Autonomic Nervous
System

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I- Physiological functions of autonomic nervous system

The Autonomic Nervous System has two branches, the Sympathetic and the
Parasympathetic, which regulate the involuntary processes of the body, the
viscera, and sense organs, glands and blood vessels. Its anatomical circuitry
is broadly dispersed, creating a general response, quite unlike the highly
specific pathways and response of the CNS. This generalized; widely
distributed structure enables it to mediate overall changes in state of the
body.
A- Function of the sympathetic nervous system:
Although situations, continually active to some degree, the sympathetic
division has the property of adjusting in response to stressful situations, such
as trauma, fear, hypoglycemia, cold, or exercise.
1- Effects of stimulation of the sympathetic division:
The effect of sympathetic output is to increase heart rate and blood pressure,
to mobilize energy stores of the body, and to increase blood flow to skeletal
muscles and the heart while diverting flow from the skin and internal organs.
Sympathetic stimulation results in dilatation of the pupils and the
bronchioles. It also affects gastrointestinal motility (it decrease), and the
function of the bladder and sexual organs.
B- Functions of the parasympathetic nervous system:
The parasympathetic division maintains essential bodily functions, such as
digestive processes and elimination of wastes, and is required for life. It
usually acts to oppose or balance the actions of the sympathetic division and
is generally dominant over the sympathetic system in "rest and digest"
situations. The parasympathetic system is not an entity as such, and never
discharges as a complete system. Instead, discrete parasympathetic fibers are

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activated separately, and the system functions to affect specific organs, such
as the stomach or eye.
II- Neurotransmitters - Receptors

All neurons are distinct anatomic units, and no structural continuity exists
between most neurons. Communication between nerve cells and between
nerve cells and effector organs, occurs through the release of specific
chemical signals, called neurotransmitters, from the nerve terminals. This
release is triggered by the arrival of the action potential at the nerve ending,
leading to depolarization. Uptake of Ca²+ ensues to initiate docking of the
synaptic vesicles and release of their contents.
The neurotransmitters rapidly diffuse across the synaptic gap (synapse) and
combine with specific receptors on the postsynaptic cell (target cell).
A- Types of neurotransmitters:
Acetylcholine and norepinephrine (noradrenaline) are the primary chemical
signals in the autonomic nervous system.
1- Acetylcholine:
The autonomic nerve fibers can be divided into two groups based on the
chemical nature of the neurotransmitter released. If transmission is mediated
by acetylcholine, the neuron is termed cholinergic.
Acetylcholine mediates the transmission of nerve impulses in both the
sympathetic and parasympathetic nervous systems.

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2- Norepinephrine and epinephrine (Noradrenaline & adrenaline):
When norepinephrine or epinephrine is the transmitter, the fiber is termed
adrenergic.
B- Receptors:
Sympathetic Parasympathetic
 Nicotinic receptors at the  Nicotinic receptors at

autonomic ganglia the autonomic
ganglia
 Adrenergic (alpha or  Muscarinic receptors
beta) receptors at the at the target tissue
target tissue
1- Adrenergic receptors:
The adrenergic receptors are of two types: alpha (α) and beta (β).
-α receptors:
They are associated mainly with increased contractibility of vascular smooth
muscle and intestinal relaxation.
α 1: contracts smooth muscle of peripheral blood vessels:
α 2: relaxes the intestinal tract
-β receptors:
They are associated with vasodilatation and relaxation of non-intestinal
smooth muscle and cardiac stimulation.
β 1: causes cardiac stimulation and lipolysis
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β 2: causes bronchodilatation. Relaxation of blood vessels (usually skeletal
muscle) and muscle glycogenolysis.
2- Cholinergic receptors:
The cholinergic receptors are of two types: muscarinic and nicotinic.
-Muscarinic receptors:
Those receptors are found on ganglia of the peripheral nervous system and
on autonomic effector organs, such as the heart, smooth muscle, brain and
exocrine glands.
-Nicotinic receptors:
Nicotinic receptors are located in the central nervous system, adrenal
medulla, autonomic ganglia, and the neuromuscular junction.
III- Sympathomimetic agents (Adrenergic Agonists)
The adrenergic drugs affect receptors that are stimulated by noradrenaline or
adrenaline (norepinephrine or epinephrine). Some adrenergic drugs act
directly on the adrenergic receptor by activating it, and are said to be
Sympathomimetic.
These drugs may either directly or indirectly stimulate the adrenergic
receptors.

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A- Major effects mediated by α and β adrenergic receptors:
α1 α2 β1 β2
Vasoconstriction Inhibition of Tachycardia Vasodilatation

norepinephrine release
Increased peripheral Inhibition of insulin Increased lipolysis Decreased peripheral
resistance release resistance
Increased blood Increased Bronchodilatation
pressure myocardial
contractility
Mydriasis Increased release Increased release of
of renin glucagon
Increased closure of Relaxed uterine

internal sphincter of smooth muscle
the bladder
B- Classification of Sympathomimetics:
Sympathomimetic agents can be classified by two different ways:
1- According to Structure:
 Catecholamines: e.g. adrenaline, noradrenaline, isoprenaline,
dopamine and dobutamine.
 Non-Catecholamines.

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2- According to relative receptor selectivity:
 Mixed agonists:
- Epinephrine (α1, α2, β1, β2)
- Dopamine (β1 > α1)
 Mainly α agonists:
- Norepinephrine (α1, α2, β1)
- Nasal decongestant non-catecholamines:
Phenylephrine, naphazoline.
 Mainly β agonists:
- Non selective β stimulants: isoprenaline
- Selective β1 stimulants: dobutamine and prenalterol;
- Selective β2 stimulants: salbutamol and terbutaline
(Bronchodilator)
C- Main adrenergic agonists:
1- Epinephrine (Adrenaline):
Therapeutic uses:
 Acute bronchial asthma: to relieve bronchospasm;
 Cardiac arrest: to restore cardiac rhythm;
 Anaphylactic shock: it is the drug of choice to overcome the
physiological effects of histamine (substance which causes
the anaphylactoid reaction)
 Prolongs the action of local anesthetics: by vasoconstriction,
it increases the time the local anesthetic is in contact with the
affected tissue.
 Stops bleeding on topical surfaces by vasoconstriction.

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Adverse effects:
 It can cause anxiety, headache, hypertension, and tachycardia.
 It should be used cautiously in-patients who have
hyperthyroidism, ischemic heart disease, and arrhythmia.
2- Norepinephrine (Noradrenaline)
Therapeutic uses:
 Hypotension and shock: to restore normal blood pressure by
its vasoconstriction effect;
 Prolongs the action of local anesthetics;
Adverse effects:
 (same of epinephrine)
3- Isoprenaline (Isoproterenol):
Therapeutic uses:
 Acute bronchial asthma;
 Cardiac stimulant in instances of heart block;
Adverse effects:
 Tachycardia;
 Arrhythmia.
4- Dopamine:
Therapeutic uses:
 Treatment of shock, including cardiogenic, trauma or
hypovolemic shock;
 Resistant heart failure;

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Adverse effects:
 Large doses have similar adverse effects of epinephrine.
5- Dobutamine:
Therapeutic uses:
 Treatment of shock;
 Acute heart failure.
6- Albuterol, Pirbuterol, and Terbutaline:
These drugs are short-acting β2 agonists used primarily as bronchodilators.
These drugs produce Bronchodilatation with less cardiac stimulation.
7- Salmeterol and Formoterol:

Salmeterol and Formoterol are β2 adrenergic selective, long-acting
bronchodilators. A single dose provides sustained Bronchodilatation over 12
hours compared with less than 3 hours for Albuterol.
IV-Adrenergic Antagonists
The adrenergic antagonists (also called blockers or sympatholytic agents)
bind to adrenoceptors but do not trigger the usual receptor-mediated
intracellular effects. These drugs act by either reversibly or irreversibly
attaching to the receptor, thus preventing its activation by endogenous
catecholamines.
A- α-adrenergic blocking agents:
 Prazosin
 Terazosin
 Doxazosin
 Tamsulosin

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1- Anti-hypertensive:
Prazosin, terazosin and Doxazosin are indicated in the treatment of
hypertension.
The first dose of these drugs produces an exaggerated hypotensive response
that can result in syncope (fainting). This action, termed as first-dose effect
may be minimized by reducing the first doses and giving the drug at
bedtime.
2- Treatment of Benign Prostatic Hypertrophy:

Tamsulosin is indicated for the treatment of benign prostatic hypertrophy.
Tamsulosin has little effect on the blood pressure.
3- Adverse effects:
α-blockers may cause dizziness, a lack of energy, nasal congestion,
headache, drowsiness, and orthostatic hypotension.
B- β-adrenergic blocking agents:

All the clinically available β-blockers are competitive antagonists.
Nonselective β-blockers act at both β1 and β2 receptors, whereas
cardioselective β antagonists primarily block β1 receptors.
Β-antagonists are mainly indicated in hypertension.
1- Propranolol
Propranolol is the prototype β-adrenergic antagonist and blocks both β1 and
β2 receptors.
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Therapeutic uses:
 Hypertension
 Glaucoma
 Migraine (prophylaxis)
 Angina perctoris
 Myocardial infarction
Adverse effects:
 Bronchoconstriction
 Arrhythmia
 Sexual impairment
 Disturbances in glucose metabolism
2- Other Nonselective β antagonists

 Timolol
 Nadolol
3- Selective β1 antagonists
 Acebutolol
 Atenolol
 Metoprolol
 Esmolol
These drugs preferentially block the β1 receptors without the unwanted
bronchoconstrictor effect of propranolol seen in asthmatic patients.

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4- Antagonists with partial agonist activity:
 Pindolol
 Acebutolol
Acebutolol and Pindolol are not pure antagonists; instead, they have the
ability to weakly stimulate both β1 and β2 receptors, and are said to have
intrinsic sympthomimetic activity (ISA). These partial agonists stimulate the
β-receptor to which they are bound, yet they inhibit stimulation. The result is
a diminished effect on cardiac rate and cardiac output compared to that of β-
blockers without ISA.
β-blockers with ISA are effective in hypertensive patients with moderate
bradycardia, because a further decrease in heart rate is less pronounced with
these drugs.
5- Antagonists of both α and ß adrenoreceptors:

 Labetolol
 Carvedilol
Labetolol and Carvedilol are reversible ß-blockers with concurrent α1-

blocking actions that produce peripheral vasodilatation, thereby reducing
blood pressure. They contrast with the other ß-blockers that produce
peripheral vasoconstriction, and are therefore useful in treating hypertensive
patients for whom increased peripheral vascular resistance is undesirable.

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V-Cholinergic agonists
A- Direct-acting cholinergic agonists
1- Acetylcholine:
Acetylcholine is rapidly inactivated by the cholinesterases, which makes it
with no therapeutic importance.
It decreases the heart rate and the cardiac output, and decreases the blood
pressure.
In the gastrointestinal tract, it increases salivary secretion and stimulates
intestinal secretions and motility.
Bronchiolar secretions are also increased.
2- Bethanecol:
It is used in urologic treatment to stimulate the atonic bladder, particularly in
postpartum postoperative nonobstructive urinary bladder.
3- Carbachol:
Carbachol is used as miotic agent in glaucoma
4- Pilocarpine:
Pilocarpine is the drug of choice in the emergency lowering of intraocular
pressure.

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B- Indirect-acting cholinergic agonists:
1- Anticholinesterases (reversible):
 Physostigmine, Neostigmine
 Tacrine, Donepezil
Physostigmine and neostigmine are mainly used in glaucoma.
Tacrine and donepezil are used to prevent the progression of Alzheimer
disease.
2- Anticholinesterases (irreversible)
These drugs are extremely toxic. They are mainly used to treat glaucoma.
VI-Cholinergic antagonists
A- Atropine
Therapeutic uses:
 Treat spastic disorders of the gastrointestinal and lower
urinary tract
 In ophthalmology, to produce Mydriasis
 To treat poisoing from irreversible anticholiesterases
 To suppress respiratory secretions prior to surgery
B- Scopolamine
Therapeutic uses:
 To prevent motion sickness
 Anti-spasmodic
C- Ipratropium
Therapeutic use:
 Treatment of asthma

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VII-Ganglionic Blockers
 Nicotine
 Trimethaphan
 Mecamylamine
Ganglionic blockers specifically act on the nicotinic receptors of both
parasympathetic and sympathetic autonomic ganglia. Some also block the
ion channels of the autonomic ganglia. These drugs show no selectivity
toward the parasympathetic or sympathetic ganglia, and are not effective as
neuromuscular antagonists. Thus, these drugs block the entire output of the
autonomic nervous system at the nicotinic receptor.
Nicotine has many undesirable actions. It is without therapeutic benefit and

is deleterious to health.
Trimethaphan is a short-acting, competitive nicotinic ganglionic blocker that
must be given by intravenous infusion. It is used for the emergency lowering
of blood pressure.
Mecamylamine is used for the treatment of moderately severe to severe
hypertension.
VIII-Neuromuscular Blocking Agents
These drugs block cholinergic transmission between motor nerve endings
and the nicotinic receptors on the neuromuscular end plate of skeletal
muscle. These neuromuscular blockers are structural analogs of
acetylcholine, and act either as antagonists (non-depolarizing type) or
agonists (depolarizing type) at the receptors on the end plate of the
neuromuscular junction.

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Neuromuscular blockers are clinically useful during surgery for producing
complete muscle relaxation, without having to employ higher anesthetic
doses to achieve comparable muscular relaxation.
A- Nondepolarizing (competitive) blockers:

 Tubocurarine
 Atracurium
 Mivacurium
These blockers are used therapeutically as adjuvant drugs in anesthesia
during surgery to relax skeletal muscle.
B- Depolarizing agents:
 Succinylcholine
Because of its rapid onset and short duration of action, Succinylcholine is
useful when rapid endotracheal intubation is required during the induction of
anesthesia. It is also employed during electroconvulsive shock treatment.

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Unit III
Autacoids

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I-Histamines and Antagonists

A- Histamine
Histamine is a chemical messenger that mediates a wide range of cellular
responses, including allergic and inflammatory reactions, gastric acid
secretion, and neurotransmission in parts of the brain.
Histamine has no clinical applications, but agents that interfere with the
action of histamine (antihistamines) have important therapeutic applications.
Histamine released in response to various stimuli exerts its effects by
binding to one or more of four types of histamine receptors (H1, H2, H3 and
H4).
H1 and H2 receptors are widely expressed and are the targets of clinically
useful drugs.
Type Function
H1 Causes vasodilatation, Bronchoconstriction, smooth muscle

activation, separation of endothelial cells, pain and itching
(especially in case of insect stings), allergic rhinitis symptoms and
motion sickness.
H2 Gastric acid secretion.
H3 Decreased neurotransmitter release.

H4 Unknown physiological role.

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B- Antihistamines
1- H1 Antihistamines:
The action of all H 1 receptor blockers is qualitatively similar.
Therapeutic uses:
 Allergic and inflammatory conditions
 Motion sickness and nausea (diphenydramine,
dimenhydrinate and meclizine that is specially used in
pregnancy)
 Somnifacients (diphenydramine)
 Adverse effects:
 Sedation
 Dry mouth
Because sedation was an important side effect of the first generation of

antihistamines, a second generation was developed in order to reduce the
potential risk of sedation.
 First generation of antihistamines:
(High potential for producing sedation, Used to treat motion sickness)
 Chlorpheniramine
 Cyclizine
 Diphenydramine
 Dimenhydrinate
 Hydroxyzine
 Meclizine
 Promethazine

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 Second generation of antihistamines:
(Weak potential for producing sedation or nonsedating)
 Cetirizine
 Desloratadine
 Loratadine
2- H2 Receptor Blockers:
 Cimetidine
 Ranitidine
 Famotidine
 Nizatidine
H2 receptor blockers have little affinity for H1 receptors. Their most
important clinical use is as inhibitors of gastric acid secretion in the
treatment of ulcers.
C-Kinines
Aprotinin, a kinine inhibitor, is used in:
- Inhibition of mediators of the inflammatory response
- Fibrinolysis
- Thrombin generation following cardiopulmonary bypass
surgery
II-Serotonin and antagonists
Serotonin or 5-Hydroxytryptamine (5-HT) is a monoamine neurotransmitter,
that is primarily found in the gastrointestinal tract, platelets, and central
nervous system of humans and animals. It is a well-known contributor to
feelings of well-being.

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Approximately 80 percent of the human body's total serotonin is located in
the enterochromaffin cells in the gut, where it is used to regulate intestinal
movements. The remainder is synthesized in serotonergic neurons in the
CNS where it has various functions, including the regulation of mood,
appetite, sleep, muscle contraction, and some cognitive functions including
memory and learning. Modulation of serotonin at synapses is thought to be a
major action of several classes of pharmacological antidepressants.
A- Serotonin-receptor agonists (5-HT-receptor agonists):
Direct-acting 5-HT-receptor agonists have widely different chemical
structures, as well as diverse pharmacological properties.
 Buspirone
 Cisapride
 Sumatriptan
 Zolmitriptan
 Naratriptan
 Rizatriptan
Buspirone is used to treat anxiety and depression.
Cisapride is used in gastrointestinal disorders.
Sumatriptan, Zolmitriptan, Naratriptan and Rizatriptan are effective, acute
antimigraine agents.
B- Serotonin-receptor antagonists (5-HT-receptor antagonists):
 Methysergide
 Trazodone
 Risperidone
 Ketanserin
 Ondansetron

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 Dolasetron
 Granisetron
Methysergide is used for the prophylactic treatment of migraine and other

vascular headaches.
Trazodone is an anti-depressant.
Risperidone is used for the management of schizophrenia.
Ondansetron, Dolasetron and Granisetron are used to prevent chemotherapy-
induced emesis.
III-Prostaglandins
Systemic administration of prostaglandins evokes a wide array of effects; the
fact that limits the therapeutic usefulness of these agents.
A- Therapeutic effects:
1-Abortion:
Several of the prostaglandins find use as abortifacients (agents causing
abortions). The most effective option available involves oral administration
mifepristone followed at least 24 hours later by the synthetic prostaglandins
analog misoprostol administered vaginally. This regimen completes abortion
rates exceeding 95%. However, infection, hemorrhage, and retained tissues
are among the more common complications.
2-Peptic Ulcers:
Misoprostol is sometimes used to inhibit the secretion of gastric acid and to
enhance mucosal resistance to injury in patients with gastric ulcer who are
chronically taking aspirin or nonsteroidal anti-inflammatory agents.

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IV-Angiotensin – Renin – Vasopressin

A- Renin-Angiotensin system:
The renin-angiotensin system plays a major role in both the short and long-
term regulation of arterial blood pressure.
Angiotensin II increases total peripheral resistance (TPR) via direct and
indirect effects on blood vessels.
Angiotensin II has also pronounced effects on renal function, reducing the
urinary excretion of Na+ and water while increasing the excretion of K+.
B- Inhibitors of the Renin-Angiotensin System:

1-Angiotensin Converting Enzyme Inhibitors (ACE-Inhibitors):
 Captopril
 Enalapril
 Lisinopril
 Benazepril
 Fosinopril
 Trandolapril
 Quinapril
 Ramipril
 Perindopril

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Therapeutic uses of ACE-I:
 Treatment of hypertension
 Management of left ventricular systolic dysfunction, Heart failure
 Acute myocardial infarction
 Prevention of cardiovascular events in high risk patients
 Chronic renal failure
 Prevention of diabetic nephropathy
Adverse effects of ACE-I:
 Hypotension
 Dry cough
 Hyperkalemia
 Skin rash
2-Angiotensin II receptor blockers (ARB):
 Candesartan
 Eprosartan
 Irbesartan
 Losartan
 Olmesartan
 Telmisartan
 Valsartan
Therapeutic uses of ARB:
 Treatment of hypertension
 Prevention of diabetic nephropathy
 Stroke prophylaxis
 Heart failure

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C-Vasopressin
1-Vasopressin analogues:
Vasopressin agonists are used therapeutically in various conditions, and its
long-acting synthetic analogue desmopressin is used in conditions featuring
low vasopressin secretion, as well as for control of bleeding and in extreme
cases of bedwetting by children. Terlipressin and related analogues are used
as vasoconstrictors in certain conditions. Vasopressin infusion has been used
as a second line of management in septic shock patients not responding to
high dose of inotropes (e.g., dopamine or norepinephrine)
2-Vasopressin antagonists:
 Conivaptan
 Reclovaptan
 Nelivaptan
 Lixivaptan
 Mozavaptan
A vasopressin receptor antagonist is an agent which interferes with action at
the vasopressin receptors. They can be used in the treatment of
hyponatremia, especially in patients with congestive heart failure or liver
cirrhosis.

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Unit IV
Central Nervous System

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I-Introduction
A- Transmission of nerve impulse
Most drugs that affect the central nervous system act by altering some step
in the neurotransmission process.
Drugs affecting the central nervous system may act presynaptically by
influencing the production, storage, release, or termination of action of
neurotransmitters. Other agents may activate or block postsynaptic
receptors.
B- Blood Brain Barrier
The BBB is semi-permeable; that is, it allows some materials to cross, but
prevents others from crossing.
1- Functions of the BBB:
 It protects the brain from foreign substances in the blood that may
injure the brain
 Maintains a constant environment for the brain
2- General properties of the BBB:
 Large molecules do not pass through the BBB easily
 Low lipid-soluble molecules do not penetrate into the brain.
However, lipid-soluble molecules rapidly cross through into the
brain.
3- The BBB can be broken down by:
 Hypertension
 Trauma
 Inflammation
 Infection

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II-General Anesthetics
A-Theories of Anesthesia
They are agents that depress the central nervous system reversibly,
producing loss of consciousness, analgesia, and muscle relaxation, with
minimal depression of the patient's vital functions.
1- Types of administration:
Anesthetic drugs can be administered:
 Inhalation
 intravenous
2- Adverse effects:
 Central nervous system toxicity (convulsions, respiratory
depression)
 Cardiovascular toxicity (hypotension, arrhythmia, cardiac arrest)
B- Inhalation anesthetics
There are gases or volatile liquids which are often mixed with oxygen and
the patient is requested to breathe the mixture.
In general, anesthesia can be well controlled with these agents because the
concentration of the agent in the blood can be increased or decreased by
either increasing or decreasing the concentration in the air that the patient is
breathing.
Inhalational anesthetics are most often used for long-term maintenance of
the anesthetic state.
Inhalation anesthetics:
 Nitrous oxide
 Ethers
 Halothane

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 Enflurane
 Methoxyflurane
C- Intravenous anesthetics
The intravenous anesthetics are sterile solutions intended to be administered
into the patient's circulatory system.
In general, the level of anesthesia is more difficult to control with
intravenous anesthetics than with inhalation anesthetics.
Intravenous anesthetics are generally employed to induce anesthesia, to
provide supplemental anesthesia, or to permit anesthesia for short operative
procedures.
Intravenous anesthetics:
 Thiopental
 Propofol
 Ketamine
 Fentanyl
 Benzodiazepines
D- Pre-anesthetic medication
Commonly, surgical patients receive one or more of the following pre-
anesthetic medications:
 Benzodiazepines (like diazepam) to allay anxiety and facilitate
amnesia
 Barbiturates (such as pentobarbital) for sedation
 Antihistamines for prevention of allergic reactions
 Drugs to reduce gastric acidity
 Opioids (such as Fentanyl) for analgesia
 Anticholinergic

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III-Local Anesthetics
There are drugs that cause reversible block of nerve conduction, producing
transient localized loss of sensation without affecting consciousness.
A- Classification according to therapeutic application:
 Topical (surface) application: cocaine, benzocaine
 Local injection : procaine, bupivacaine, mepivacaine
 Both topical and local injection: lidocaine
B- Adverse effects of local anesthetics:

 Allergic dermatitis may occur with surface anesthesia
 Faulty intravascular injection may cause central nervous system
toxicity (convulsions, respiratory depression) or cardiovascular
toxicity (hypotension, cardiac arrest).

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IV-Sedatives and Hypnotics

A- Introduction
Anxiety is an unpleasant state of tension, apprehension, or uneasiness -a fear
that seems to arise from an unknown source. Disorders involving anxiety are
similar to those of fear (such as tachycardia, sweating, trembling, and
palpitations) and involve sympathetic activation.
Because all of the antianxiety drugs (sometimes called anxiolytic or minor
tranqulizers) cause some sedation, the same dugs often function clinically as
both anxiolytic and hypnotic (sleep-inducing) agents.
(All sedatives become hypnotics at large doses)
B- Benzodiazepines
Benzodiazepines are the most widely used anxiolytic drugs. They have
largely replaced barbiturates in the treatment of anxiety, because the
benzodiazepines are safer and more effective.
The target for benzodiazepines actions are the GABA receptors.
1- Actions:
 Reduction of anxiety
 Sedative and hypnotic actions
 Amnesia
 Anticonvulsant
 Muscle relaxant
2- Dependence:
Psychological and physical dependence on benzodiazepines can develop if
high doses of the drug are given over a prolonged period. Abrupt
discontinuation of the benzodiazepines results in withdrawal symptoms,
including confusion, anxiety, agitation, restlessness, insomnia, and tension.

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3- Adverse effects:
 Drowsiness
 Impaired performance and judgment
 Central nervous system and cardiovascular toxicity
 Dependence
4- Classification of benzodiazepines according to duration of action:
 Ultra short-acting (4 hours): Midazolam, Triazolam
 Intermediate-acting (5-20 hours): Lorazepam, Oxazepam
 Long-acting (60 hours): Diazepam, Clonazepam
C- Other anxiolytic and hypnotic agents
 Zolpidem
 Zaleplon
 Buspirone
D- Benzodiazepines antagonist
Flumanezil is a GABA receptor antagonist that can rapidly reverse the
effects of benzodiazepines. The drug is available for intravenous (IV)
administration only.
E- Barbiturates
The barbiturates were the mainstay of treatment used to sedate the patient or
to induce and maintain sleep. Today, they have been largely replaced by the
benzodiazepines, primarily because barbiturates induce tolerance, drug-
metabolizing enzymes, physical dependence, and very severe withdrawal
symptoms. Foremost is their ability to cause coma in toxic doses. Certain
barbiturates, such as the very short-acting thiopental, are still used to induce
anesthesia.

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1- Actions:
 Depression
Of the CNS. At low doses, the barbiturates produce sedation
(Calming effect, reducing excitement). At higher doses, the drugs
cause hypnosis, followed by anesthesia, and finally coma and death.
 Respiratory depression
2- Therapeutic uses:
 Anesthesia (Thiopental)
 Anticonvulsant (Phenobarbital)
 Anxiety
3- Classification of Barbiturates according to the duration of action:
 Ultra short-acting (15-30 minutes): Thiopental
 Short-acting (2-4 hours): Pentobarbital, Secobarbital
 Intermediate-acting (4-6 hours): Amobarbital
 Long-acting (6-8 hours): Phenobarbital
F- Nonbarbiturate Sedatives
 Chloral hydrate
 Antihistamines
 Ethanol

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V-Antiepileptic drugs
Epilepsy is a chronic, usually life-long disorder characterized by recurrent
seizures or convulsions and usually episodes of unconsciousness and/or
amnesia. Convulsion is a violent involuntary contraction or series of
contractions of the voluntary muscles.
A- Hydantoins
Phenytoin is a drug of choice for initial therapy, particularly in treating
adults.
B- Carbamazepine
Carbamazepine is highly effective and is often the drug of first choice.
C- Barbiturates
Phenobarbital has antiepileptic activity.
Primdone ressembles Phenobarbital in its anticonvulsant activity.
D- Valproic acid
Valproic acid has multiple actions and is a broad-spectrum anticonvulsant,
but because of its hepatotoxic potential, it is a second choice.
E- Succinimides
Ethosuximide is the first choice in absence seizures.
F- Benzodiazepines
Several of the benzodiazepines show antieplipeptic activity: Diazepam,
Lorazepam, Clonazepam, clonazepate.
G- Newer antiepileptic drugs
 Felbamate
 Gabapentin
 Lamotrigine
 Topiramate

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 Tiagabine
VI-Agents used in the treatment of Parkinson disease

A- Parkinson disease
Parkinsonism is a movement disorder characterized by muscle rigidity,
tremors and postural instability.
It is due to dopamine deficiency in the basal ganglia resulting in imbalance
of dopaminergic (inhibitory) and cholinergic (excitatory) influences on the
extrapyramidal.
The aim of antiparkinsonian drugs is to increase dopamine in the basal
ganglia.
A- Levodopa and Carbidopa
Levodopa is a metabolic precursor of dopamine. It restores dopamine levels
in the extrapyramidal centers.
The effects of levodopa on the CNS can be greatly enhanced by
coadministrating carbidopa. Carbidopa diminishes the metabolism of
levodopa in the gastrointestinal tract and peripheral tissues.
B- Selegeline
Selegeline selectively inhibits MAO B. By thus decreasing the metabolism
of dopamine, selegeline has been found to increase dopamine levels in the
brain.
C- Dopamine receptor agonists
 Bromocriptine
 Pergolide
 Pramipexole
 Ropinirole

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D- Amantadine
It was accidentally discovered that the antiviral drug amantadine, effective in
the treatment of influenza, has an antiparkinsonism.
VII-Antipsychotic agents (Neuroleptic drugs)

Psychosis (psychotic disorders) is a group of disorders with more or less
severe disturbances of thought, mood and/or behavior.
Schizophrenia is a particular kind of psychosis characterized mainly by
thought disorders, delusions and hallucinations due to central dopamine
overactivity.
Neuroleptic drugs (also called antischizophrenic drugs, antipsychotic drugs
or major tranquilizers) are used primarily to treat schizophrenia and manic
states and delirium.
A- Typical neuroleptic
The typical neuroleptic drugs have several adverse effects:
 Parkinsonian-like syndrome
 Neuroleptic malignant syndrome (rigidity, autonomic instability)
 Anticholinergic effects (atropine-like)
 Sedation
 Hyperprolactinemia
 Postural hypotension
1- Typical neuroleptic (Low potency)
 Chlorpromazine
 Promethazone

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2- Typical neuroleptic (High potency)
 Fluphenazine
 Haloperidol
 Pimozide
B- Atypical neuroleptic
The newer antipsychotic drugs are referred to as "atypical", because they
have fewer extrapyramidal adverse effects and anticholinergic side effects
than the typical antipsychotics.
Atypical neuroleptics:
 Clozapine
 Olanzapine
 Risperidone

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VIII-Antidepressant
The symptoms of depression are intense feelings of sadness, hopelessness,
and despair, as well as the inability to experience pleasure in usual activities,
changes in sleep patterns and appetite, loss of energy, and suicidal thoughts.
Most clinically useful antidepressant drugs potentiate, either directly or
indirectly, the actions of epinephrine and/or serotonin in the brain.
A- Selective Serotonin Re-Uptake Inhibitors SSRIs
 Citalopram
 Escitalopram
 Fluoxetine
 Fluvoxamine
 Paroxetine
 Sertraline
B- Serotonin/Norepinephrine Re-Uptake Inhibitors
 Venlafaxine
C- Atypical antidpressants
 Bupropion
 Mirtazapine
 Nefazodone
 Trazodone
D- Tricyclic antidpressants
 Amitriptyline
 Clomipramine
 Despiramine
 Imipramine

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 Nortriptyline
IX-CNS stimulants
A- Psychomotor stimulants
 Amphetamine
 Atomoxetine
 Caffeine
 Cocaine
 Methylphenidate
 Nicotine
 Theophylline
They have limited therapeutic use.
They can have inhibitory effect on the appetite.
Amphetamine is used in the Attention deficit hyperactivity disorder.
B- Hallucinogens
 Lysergic acid diethylamide LSD
 Tetrahydracannabinol THC
X-Narcotic analgesics
Opiates are natural alkaloids derived from Papaver somniferum plant.
Opiods include both naturally occurring opiates and similar synthetic drugs.
Narcotics are drugs that produce drowsiness with analgesia. They are usually
addictive.
A- Morphine and related opioids:
1- Morphine
It is used in analgesia in severe pain.
Adverse effects:
 Addiction
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 Respiratory depression, bronchospasm
 Postural hypotension
 Nausea, vomiting, and constipation
 Urine retention
2- Codeine (methylmorphine)
Codeine is less potent than morphine in all features except in cough
suppression.
The clinical use of codeine is as central antitussive.
B- Meperidine
Meperidine is a synthetic opioid structurally unrelated to morphine. It is less
potent than morphine in al features. It also has less addiction liability,
respiratory depression and bronchospasm.
Its therapeutic use is as analgesic for acute pain.
C- Methadone
Methadone is a synthetic, orally effective opioid that is approximately equal
in potency to morphine but induces less euphoria and has somewhat longer
duration of action.
Methadone is used in the controlled withdrawal of dependent abusers from
heroin and morphine. Orally administered, methadone is substituted for the
injected opioid.
D-Fentanyl
Fentanyl has 100-fold the analgesic potency of morphine, and is used in
anesthesia.
Three drugs related to Fentanyl – sulfentanil, alfentanil, remifentanil- are
also used as analgesics.

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E- Other analgesic
1- Propoxyphene
It is used as an analgesic to relieve mild to moderate pain.
2- Tramadol
It is used to manage moderate to moderately severe pain
F-Antagonists
In patients dependent on opioids, antagonists rapidly reverse the effect of
agonists and precipitate the symptoms of withdrawal.
 Naloxone
 Naltrexone

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XI-Drugs used in migraine

A- Pathophysiology of Migraine
The stage of aura: sudden release of serotonin of unknown cause, which
causes vasoconstriction of cerebral blood vessels, leading to visual, olfactory
or auditory disturbances.
The stage of headache: prolonged vasoconstriction → accumulation of
metabolites → severe vasodilatation → perivascular edema and headache.
B- Drugs used during acute attack:
Ergotamine
Sumatriptan
Analgesics
C-Prophylaxis
Serotonin receptor blockers : methysergide
Beta-blockers : propranolol (unknown mechanism)
Calcium channel blockers : verapamil
XII-Drugs of abuse
A-Opioids and Morphine derivatives:
 Codeine
 Fentanyl
 Heroin
 Morphine
 Opium
 Oxycodone

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They cause pain relief, euphoria, drowsiness, nausea, constipation,
confusion, sedation, respiratory depression and arrest, tolerance, addiction,
unconsciousness, coma, death.
B-Barbiturates
 Amytal
 Nembutal
 Phenobarbital
They cause reduced anxiety, feeling of well-being, lowered inhibitions,
slowed pulse and breathing, lowered blood pressure, poor concentration,
drowsiness, unusual excitement, poor judgment, slurred speech, dizziness,
life-threatening withdrawal, addiction, respiratory depression and arrest,
death.
C-Stimulants
Most of them cause increased heart rate, increased blood pressure, increased
metabolism, feelings of exhilaration, energy, increased mental alertness,
reduced appetite, weight loss, heart failure, nervousness, and insomnia.
1-Amphetamine:
It also causes rapid breathing, tremor, loss of coordination, irritability,
anxiousness, restlessness, delirium, panic, impulsive behavior,
aggressiveness, tolerance, addiction, psychosis.
2-Cocaine:
It also causes increased temperature, chest pain, respiratory failure, nausea,
abdominal pain, strokes, seizures, headaches, malnutrition, panic attacks.

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3-Nicotine:
It also causes all the additional effects attributable to tobacco exposure,
adverse pregnancy outcomes, chronic lung disease, cardiovascular disease,
stroke, cancer, tolerance, addiction.
D-Hallucinogens:
 LSD
 Mescaline
They cause altered states of perception and feeling, nausea, increased body
temperature, increased heart rate, increased blood pressure, loss of appetite,
sleeplessness, numbness, weakness, tremors.
E-Inhalants:
 Solvents (paint, thinners, gasoline, glues)
 Gases (butane, propane, aerosol propellants, nitrous oxide)
 Nitrites
 Laughing gas
They cause stimulation, loss of inhibition, headache, nausea or vomiting,
slurred speech, loss of motor coordination, wheezing, unconsciousness,
cramps, weight loss, muscle weakness, depression, memory impairment,
damage to cardiovascular and nervous systems, sudden death.

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Unit V
Drugs used for respiratory tract
disorders

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I-Asthma
A- Asthma
Asthma may be a chronic or acute condition involving the respiratory
system, in which the airways (the bronchi and bronchioles) become inflamed
and constrict, and are lined with large amounts of mucus, often in response
to one or more triggers.
These episodes may be triggered by such things as exposure to an
environmental stimulant such as allergen, environmental tobacco smoke,
cold or warm air, perfume, pet dander, moist air, exercise or exertion, or
emotional stress. In children, the most common triggers are viral illnesses
such as those that cause common cold.
Airflow obstruction in asthma is due to Broncho-constriction that results
from contraction of bronchial smooth muscle, inflammation of the bronchial
wall, and increased mucous secretion.
Asthmatic attacks may be related to triggers, leading to bronchial
hyperactivity and inflammation of the airway mucosa. The airway narrowing
causes symptoms such as wheezing, shortness of breath, chest tightness, and
coughing.
The symptoms of asthma may be effectively treated by several drugs, but no
agent provides a cure for this disease.

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B- Adrenergic drugs
Inhaled adrenergic agonists with β2 activity are the drugs of choice for mild
asthma. Direct-acting β2 agonists are potent bronchodilators that relax
airway smooth muscle.
1- Short-acting drugs:
 Salbutamol
 Terbutaline
 Albuterol
 Pirbuterol
Most clinically useful β2 have a rapid onset of action (15 to 30 minutes) and
provide relief for 4 to 6 hours. They are used for symptomatic treatment of
bronchospasm and as "rescue agents" to combat acute bronchoconstriction.
β2 agonists have no anti-inflammatory effects, and they should never be
used as the sole therapeutic agents for patients with chronic asthma.
Side effects:
 Tremor (the major side effects)
 Elevated heart rate or blood pressure (at high doses)
2- Long-acting drugs:
 Salmeterol
 Formoterol
Salmeterol and Formoterol are β2-adrenergic selective, long-acting
Bronchodilator

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C- Corticosteroids
Inhaled glucocorticoids are the drugs of the first choice in patients with
moderate to severe asthma that require inhalation of β2-adrenergic agonists
more than 2 times per week.
Severe asthma may also require systemic glucocortcoids, usually for a short
time. No other medications are as effective as inhaled corticosteroids in the
longer-term control of asthma in children and adults. Inhaled glucocorticoids
often reduce or even eliminate the need of oral glucocorticoids in patients
with severe asthma. To be effective in controlling inflammation,
glucocorticoids must be taken continuously.
Side effects:
Oral or parenteral glucocorticoids have a variety of potentially serious side
effects. However, inhaled glucocorticoids have few systemic effects.
D- Antileukotriene drugs
These drugs are approved for the prophylaxis of asthma. However, they are
not effective in situations when immediate Bronchodilatation is required.
 Montelukast
 Zafirlukast
E- Cromolyn and Nedocromil
These drugs are effective prophylactic anti-inflammatory agents. However,
they are not useful in managing an acute asthmatic attack, because they are
not direct bronchodilators.

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F- Cholinergic antagonists
Anticholinergic agents are generally less effective than β2-adrenergic
agonists.
 Ipratropium
 Tiotropium
G- Theophylline
Theophylline is a bronchodilator that relieves airflow obstruction in chronic
asthma and decreases its symptoms.
II-Drugs used for Cough
A cough medicine is a drug that treat coughing and related conditions.
Dry coughs are treated with cough suppressants (antitussives) that suppress
the body's urge to cough, while productive coughs are treated with
excpectorants that loosen mucus from the respiratory tract.
A- Antitussives
 Codeine
 Dextromethorphan
 Hydrocodone
 Noscapine
B- Expectorants
 Guafenesin
 Potassium iodide
C- Mucolytics
 Acetylcysteine
 Bromhexine
 Carbocisteine
 Ambroxol

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Unit VI
Hormones and Antagonists

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I-Review of different endocrine glands in body

The endocrine glands are glands of internal secretion (rather than external,
like the sweat glands and digestive glands).
This internal secretion results from the fact that these glands have no ducts
(ductless glands).
Their secretions are called hormones, which are carried by the bloodstream
to the target organs.
The activity of the target organ, in turn, affects the activity of the endocrine
organ (reverse or feedback mechanism).
The figure below shows the better known endocrine glands and their
location:

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II-Idea about Hypothalamic and anterior pituitary

hormones

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A-Hypothalamic hormones:
Hypothalamus produce specific secretions called releasing factors. They
stimulate the cells of the anterior pituitary gland to secrete their specific
hormones:
 Growth hormone-releasing hormone (GHRH): stimulates the release

of GH.
 Growth hormone-inhibitory hormone (GRIH) (somatostatin):
inhibits the release of GH (and also other peptide hormones including
insulin, glucagon, and gastrin)
 Thyrotropin-releasing hormone (TRH): stimulates the release of TSH.
 Corticotropin-releasing hormone (CRF): stimulates the release of
ACTH.
 Gonadotropin-releasing hormone (GnRH): stimulates the release of
FSH and LH.
 Prolactin-releasing hormone (PRH): stimulates the release of
Prolactin.
 Prolactin-inhibitory hormone (PRIH): inhibits the release of Prolactin
and could be identical with dopamine.
B-Anterior pituitary hormones:
The anterior pituitary gland produces many hormones. In general, they
stimulate the target organs to develop or produce their own products. This
stimulating effect is referred to as trophic.
 Growth Hormone (GH) (Somatotropin) (Somatotrophic Hormone):

stimulates the growth of the body in general. When this hormone is

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deficient, dwarfism results. When it is present in excess amounts,
giantism results.
 Thyroid-stimulating hormone (TSH) (thyrotropin): stimulates the
thyroid gland to produce its hormones.
 Adrenocorticotropic hormone (ACTH) ( corticotropin): stimulates
the adrenal (suprarenal) cortex to produce its hormones.
 Luteinizing hormone (LH): stimulates ovulation and luteinization of
ovarian follicles in females and promotes testosterone production in
males.
 Follicle-stimulating hormone (FSH): stimulates ovarian follicle
growth in females and stimulates spermatogenesis in males.
 Prolactin: stimulates milk production and maternal behavior in
females.
III-Thyroid and anti-thyroid drugs
A-Synthesis of thyroid hormones in body:
A normal rate of thyroid hormone synthesis depends on an adequate intake
of iodine. Synthesis and release of thyroid hormones occurs in the following
steps:
1- Iodide uptake (trapping): circulating Iodide is trapped by gland.
2- Oxidation of iodide: by peroxidase enzyme to form active iodine.
3- Organification of iodine: iodine is bound to tyrosine to form
iodotyrosines (monoiodotyrosine MIT and diiodotyrosine DIT).
4- Coupling of iodotyrosines: to form triiodothyronine (T3) and
tetraiodothyronine (T4).
5- Storage: T3 & T4 are stored combined with globulin inside thyroid
acini to form thyroglobulin .

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6- Release: T3 & T4 are released when needed into blood after splitting
of thyroglobulin by protease enzyme.
The thyroid releases predominantly T4. However, the active form appears to
be T3; T4 is converted in part to T3.
B-Thyroid hormones:
Thyroid gland secretes three hormones:
 Triiodothyronine (T3).
 Thyroxin (tetraiodothyronine or T4).
These hormones are responsible for optimal growth, development, function,
and maintenance of all body tissues.
 Calcitonin: Important in the regulation of calcium metabolism in the
body.
C-Thyroid hormones preparations:
1-Agonist preparations:
 Synthetic:
- Levothyroxine (T4): long plasma half-life, used for thyroid
hormone replacement therapy in hypothyroid patients.
- Liothyronine (T3): short plasma half-life, used in myxedema
coma.
- Liotrix (4:1 mixture of levothyroxine and liothyronine): used
as levothyroxine. It does not appear that it offers any
therapeutic advantage over levothyroxine alone.
 Animal origin (desiccated thyroid):
derived from dried and defatted thyroid glands of domestic animals (bovine,
ovine, or porcine). These preparations are rarely used today.

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Adverse effects of thyroid preparations:

The most common adverse effects are the result of a drug overdose (i.e.,
symptoms of hyperthyroidism).
They include cardiac palpitation and arrhythmias, tachycardia, weight loss,
tremor, headache, insomnia, and heat intolerance.
2-Thyroid hormone antagonists:
These drugs are used in the treatment of hyperthyroidism.
 Thioamides
Propylthiouracil, Carbimazole, Methimazole
- Mechanismof action: they inhibit peroxidase enzyme, inhibit
organification and Coupling.
- Uses: mild cases of thyrotoxicosis, preoperative in thyrotoxicosis.
- Side effects: agranulocytosis, allergy (rash, fever…), pass through
placenta and milk→ hypothyroidism in infant.
 Anion Inhibitors
Potassium perchlorate, Thiocyanate.
- Mechanism of action: inhibition of iodide uptake (compete with
iodide for iodide transport system). These effects can be overcome
by large doses of iodides.
- Uses: iodine-induced hyperthyroidism.
- Side effects: potassium perchlorate causes aplastic anemia.
 Iodides
Potassium iodide (KI), Lugols iodine(iodine + KI)
- Mechanism of action: transient inhibition of iodide uptake, high
doses also inhibit the secretion of thyroid hormone. The gland
escapes this inhibition with long term use.
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- Uses: preoperative in thyrotoxicosis to decrease the gland size and
vascularity.
- Side effects: iodine-induced thyrotoxicosis, allergy (rash, fever…),
inflammation of the salivary glands
 Radioactive Iodine: I131
- Mechanism: destroy thyroid tissue through β rays.
- Uses: hyperthyroidism in old age or in recurrence, failure of other
therapy, metastatic cancer thyroid.
- Side effects: hypothyroidism.

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IV- Adrenocorticoeteroids
They are steroidal hormones secreted by adrenal cortex.
They can be synthetic or naturally occurring:
Agent Activity 1 Available Forms

Anti- Salt-
inflammatory retaining
Glucocorticoids
Short- to medium-acting
Cortisol 1 1 Oral, Injection,
Topical
Cortisone 0.8 0.8 Oral, injection,
Topical
Prednisone 4 0.3 Oral
Prednisolone 5 0.3 Oral, Injection,
Topical
Methylprednisolone 5 0 Oral, Injection,
Topical
Meprednisone 5 0 Oral, Injection
Intermediate-acting
Triamcinolone 5 0 Oral, Injection,
Topical
Paramethasone 10 0 Oral, Injection
Fluprednisolone 15 0 Oral
Long-acting

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Betamethasone 25–40 0 Oral, Injection,
Topical
Dexamethasone 30 0 Oral, Injection,
Topical
Mineralocorticoids
Fludrocortisone 10 250 Oral, Injection,
Topical
Desoxycorticosterone 0 20 Injection, Pellets
Acetate (DOCA)
1 Potency relative to hydrocortisone.
N.B. Adrenal cortex also secretes sex hormones in small amounts:
 Androgens ( dehydroepiandrosterone DHEA, androstenediol and
androstenedione). However, they have a weak androgenic or
estrogenic activity, mostly by peripheral conversion to testosterone
and dehydrotestosterone or estradiol and estrone.
 Progesterone in smaller amounts.
A-Clinical uses of steroids:
 Replacement therapy: Addison’s disease (primary adrenal
insufficiency): glucocorticoids e.g. Cortisol + mineralocorticoids
 Supplementary therapy: glucocorticoids
- Anti-inflammatory and antiallergic: Rheumatic carditis,
bronchial asthma, ulcerative colitis, rheumatic and collagen
diseases, allergy…….
- Anti shock and anti stress.

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 Suppression therapy: glucocorticoids suppress rejection in tissue
transplantation, shrinkage of lymphatic tissue in lymphoma and
leukemia.
B-Adverse effects of corticoids:
With prolonged use:
 Hyperglycemia
 Peptic ulceration
 Osteoporosis
 Sodium and water retention
 Depression
 Thinning of skin
 Increased susceptibility to infection
 Cushing syndrome
 Cataracts and glaucoma
Sudden withdrawal induces Addison crisis (acute adrenal insufficiency)
C-Antagonists of adrenocortical agents:
1-Steroid synthesis Inhibitors:
 Metyrapone,
 Aminoglutethimide,
 Ketoconazole
Clinical use:
- Cushing’s syndrome (excess secretion of glucocorticoids)
2-Glucocorticoid receptors Antagonists:
 Mifepristone

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Clinical use:
- Cushing’s syndrome and anti-progesterone.
3-Mineralocorticoid (aldosteron) receptors Antagonists:
 Spironolactone,
 Eplerenone
Clinical use:
- Hyperaldosteronism,
- Diuretic,
- Female hirsutism (spirinolactone has androgen antagonist effect)
V-Gonadal hormones
A-Estrogen:
 Natural:
- Estradiol (the major natural estrogen),
- Estrone,
- Estriol.
 Synthetic:
- Ethinyl estradiol,
- Mestranol,
- Diethylstilbestrol (DES)
1-Functions of Estrogen:
 Endometrial proliferation,
 Increases myometrial excitability,
 Genital development,
 Stromal development of breast,
 Fat deposition.

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2-Clinical use of Estrogen analogues:
 Female hypogonadism,
 Hormone replacement therapy in menopause,
 Contraception,
 Uterine bleeding,
 Dysmenorrhea,
 Prostate carcinoma.
3-Adverse effects:
 Nausea,
 Migraine,
 Breast tenderness,
 Cholestasis,
 Increased blood coagulation (risk of thrombosis),
 Endometrial hyperplasia,
 Increased risk of endometrial and breast carcinoma.
4- Estrogen Antagonist:
 Clomiphene
Clinical use:
- Induction of ovulation in women (fertility drug)
Adverse effect:
- Ovarian hyper stimulation (multiple births).
5-Selective estrogen receptor modulators:
 Tamoxifen,
 Raloxifene
These are compounds whose estrogenic activities are tissue-selective
Tamoxifen:

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- Agonist in bone, Antagonist in breast, Partial agonist in endometrium.
- Clinical use: metastatic breast cancer.
- Adverse effect: increase risk of thrombosis, cataract, and increase risk
of endometrial carcinoma.
Raloxifene:
- Agonist in bone, Antagonist in breast and uterus.
- Clinical use: osteoporosis as it reduces the rate of bone loss.
- Adverse effect: increased risk of thrombosis
B-Progestin
 Natural:
- Progesterone (the major natural progestin)
 Synthetic:
- Medroxyprogesteron,
- Norethindrone,
- Norgestrel
1-Function of Progestin:
 Stimulation of endometrial glandular secretions,
 Maintenance of pregnancy,
 Decreased endometrial excitability,
 Production of thick cervical mucus which inhibits sperm entry into the
uterus,
 Uterine smooth muscle relaxation
2-Clinical use:
 Contraception,
 Hormone replacement therapy (with estrogen to decrease risk of
endometrial carcinoma)

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3-Adverse effects:
 Decrease of HDL levels (good cholesterol) and increase of LDL (bad
cholesterol),
 Glucose intolerance,
 Anti-estrogenic (block lipid changes).
4- Progestin Antagonist:
 Mifepristone (RU 486)
Clinical use:
- termination of early pregnancy (abortifacient),
- antiglucocorticoid.
Adverse effect:
- abdominal pain,
- uterine bleeding may be heavy.
C-Hormonal contraception:
1-Oral:
 Combination method:
Estrogen (e.g.ethinyl estradiol) + Progestin (e.g.norethindrone)
Taken daily for 21 days, followed by a 7 days free period).
 Minipill:
Containing Progestin (e.g.norethindrone) only
Taken daily without interruption.
 Post-coital (emergency):
- Estrogen alone in high dose (taken within 72 hours of intercourse, followed
after 12 hours by a second dose.
- Mifepristone with misoprostol (taken once).

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2-Parentral (depot contraception):
Medroxyprogesterone (given intramuscular every 3 months).
3-Implanted:
Norgestrel subcutaneous implantation (lasts up to 5 years)
Mecanism of action of hormonal contraception:
- Estrogen→↓ FSH, progestin→↓LH, so; inhibit ovulation.
- Increase viscosity of cervical mucus so; impair its penetration by sperms.
- Induce endometrial changes that prevent implantation.
- Interfere with uterine and fallopian tubes contraction.

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VI-Drugs used in Diabetes Mellitus (DM)

A-Different forms of diabetes mellitus:
 Primary DM:
- Insulin dependant (Type 1) DM: due to insulin deficiency, occur
usually in young non obese people and treated by insulin.
- Non insulin dependant (Type 2) DM: due to insulin resistance, occur
usually in older obese people and treated by oral antidiabetics ±
insulin.
- Mature onset diabetes in the young (MODY type): intermediate type
between type 1 & type 2, occur in young obese people and treated by
oral antidiabetics.
 Secondary DM: secondary to other causes e.g. chronic pancreatitis.
 Gestational DM: occurs during pregnancy.
 Impaired glucose tolerance: glucose levels between normal and
diabetic levels, 5-10% develop diabetes.
B-Insulin
1-Chemistry of insulin:
Insulin is a small protein secreted from ß-cells of pancreas. It contains 51
amino acids arranged in two chains (A and B) linked by disulfide bridges;
there are species differences in the amino acids of both chains.
It is secreted as pro-insulin, a long single-chain protein molecule, which split
into insulin and a residual connecting segment called C-peptide.
2-Mechanism of action:
Insulin is bound by specialized receptors that are found on the membranes of
most tissues.

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The insulin receptor consists of two linked unites, each containing an
extracellular subunit, and a subunit that spans the membrane and contains a
tyrosine kinase, which becomes activated when the insulin molecule bind to
the extracellular subunit.
This results in multiple effects including translocation of glucose
transporters to the cell membrane with a resultant increase in glucose uptake
(as well as K); glycogen synthesis; protein synthesis, lipogenesis.
3-Pharmacokinetics:
Being a polypeptide hormone, insulin is inactivated by the proteolytic
enzymes if administered orally.
It is usually administered subcutaneously.
Once insulin enters the circulation, it is bound by specialized receptors that
are found on the membranes of most tissues. Its plasma half-life is less than
10 minutes.
Hepatic insulinases destroy approximately 50% of circulating insulin, with
the remainder degraded by circulating proteases. Therefore, only a relatively
small amount of the total endogenous insulin secreted ever reaches the
peripheral tissues.
In the kidney, insulin that undergoes glomerular filtration is almost
completely reabsorbed and metabolized within the proximal convoluted
tubules of the nephrons
4-Metabolic effects of insulin deficiency:
 On carbohydrates:
Glucose does not enter the cells to be utilized leading to hyperglycemia ±
glucosuria.

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 On fats:
Release fatty acids from adipose tissues (↑free fatty acids) leading to fatty
liver, atherosclerosis and keton body formation (to supply energy in absence
of glucose utilization).
 On proteins:
Muscle wasting.
5-Routes of administration:
 Insulin is usually administered subcutaneously.
 Intramuscular injections of insulin are used less often because
absorption is more rapid.
 In emergencies, such as severe diabetic ketoacidosis, insulin can be
given intravenously.
 Clinical studies are examining the efficacy and safety of inhaled
insulin.
6-Preparations:
Drug Onset Peak Duration
Rapid Acting
Lispro (Humalog) 10–20 1–2 hr 2–4 hr
min
Insulin Aspart (Novolog) 10–20 1 hr 3–5 hr
min
Short Acting
Regular 30–60 2–3 hr 5–7 hr
min
Prompt Insulin Zn Suspension (Semi- 30–60 2–3 hr 5–7 hr
Lente) min

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Intermediate Acting
Isophane Insulin Suspension (NPH) 1–2 hr 5–7 hr 13–18 hr
Insulin Zn Suspension (Lente) 1–3 hr 4–8 hr 13–20 hr
Long Acting
Extended Zn Suspension (Ultralente) 2–4 hr 8–14 18–36 hr
hr
Insulin Glargine (Lantus) 2–hr None up to 24
hr
Insulin Mixtures(biphasic)
70% NPH +30% regular
50% NPH +50% regular
7-Adverse effects:
 The most common side effect is hypoglycemia and hypoglycemic
coma.
 Weight gain (due to increased caloric storage of glucose by insulin).
 Insulin resistance (due to Insulin-binding immunoglobulins).
 Allergic reactions (due to the use of animal-derived insulins)
 Repeated subcutaneous injections can cause local lipodystrophy
(lipohypertrophy or lipoatrophy), which may alter the insulin
absorption from this site.
 Hypokalemia can follow acute insulin administration
C-Oral hypoglycemic agents
 Insulin secretagogues (sulfonylureas, meglitinides, D-phenylalanine
derivatives),
 Biguanides,

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 Thiazolidinediones,
 α-Glucosidase inhibitors.
1-Sulphonyl ureas
 First-Generation Sulfonylureas:
- Tolbutamide
- Tolazamide
- Acetohexamide
- Chlorporpamide (long-acting)
 Second-Generation Sulfonylureas: more potent and less drug
interactions than 1st generation.
- Glipizide
- Gliclazide
- Glimepiride
- Glyburide
Mechanism of action:
Sulfonylureas are Insulin secretagogues. They stimulate secretion of
endogenous insulin and increases sensitivity of insulin receptors (insulin
sensitizer).
Adverse effects:
- Hypoglycemia (mainly with 2nd generation drugs),
- Weight gain,
- Hypersensitivity,
- Drug interactions (mainly with 1st generation drugs)→ increase
hypoglycemia with cimetidine, insulin, salicylates, sulfonamides

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2-Bigunides:
 Metformin
The exact mechanism is not clear, but it does not depend on the presence of
functioning pancreatic B cells. It is proposed to be through stimulation of
glycolysis in tissues, reduction of gluconeogenesis and slowing of glucose
absorption.
Adverse effects:
- lactic acidosis,
- GI disturbance ( nausea, vomiting, abdominal discomfort, and
diarrhea)
Hypoglycemia during biguanide therapy is essentially unknown. These
agents are therefore more appropriately termed "euglycemic" agents.
3-Other newer agents:
 Meglitinides: Repaglinide
- Mechanism of action: Insulin secretagogues i.e. stimulate secretion
of endogenous insulin (rapid onset of action, so taken just prior to
meals).
- Adverse effects: GI disturbance.
 D-phenylalanine derivatives: Nateglinide
- Mechanism of action: Insulin secretagogues i.e. stimulate secretion
of endogenous insulin (rapid onset of action, so taken just prior to
meals).
- Adverse effects: rare; hypersensitivity.
 Thiazolidinediones (Glitazones): Pioglitazone, Rosiglitazone

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- Mechanism of action: Insulin sensitizer i.e. increases sensitivity of
insulin receptors.
- Adverse effects: edema, weight gain, mild anemia.
 α-Glucosidase inhibitors: Acarbose, Miglitol
- Mechanism of action: Inhibit intestinal brush border α-
glucosidases; thus delaying digestion of carbohydrate and
absorption of glucose.
- Adverse effects: GI disturbance (flatulence, diarrhea, and
abdominal pain) due to fermentation of undigested
carbohydrate in the colon.

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Unit I- Analgesics, Antipyretics and

Anti-inflammatory agents

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I-The inflammatory response:

Inflammation begins when a stimulus, such as infection, physical or
chemical stress, produces cellular damage.
This damage initiates the chemo-attraction of inflammatory cells, and
activation of these cells to release inflammatory mediators.
A-Inflammatory mediators:
Among the most important inflammatory mediators are:
 Eicosanoids,
 Biological oxidants,
 Cytokines,
 Adhesion factors,
 Digestive enzymes.
B-Phases of the inflammatory response:
 The rapid phase occurs within seconds to minutes and consists of
vasodilatation, increased blood flow, edema and pain. During this
phase, moderate amounts of inflammatory mediators are produced.
 The chronic phase occurs over months to years and is marked by
dramatically increased production of inflammatory mediators.
The need for anti-inflammatory drugs arises when the inflammatory
response is inappropriate, aberrant, sustained, or causes destruction of tissue.

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II-Non steroidal anti-inflammatory drugs (NSAIDs)

A-Mechanism of action:
They exert their action through inhibition of cyclo-oxygenase enzyme
(COX) causing decrease in the formation of inflammatory mediators
(prostaglandins, prostacyclins and thromboxanes).
There are 2 types of COX:
 COX-1: it is the constitutive form, present in many normal tissues.
 COX-2 : it is the inducible form, produced at site of inflammation (not
found in normal tissues)
The pharmacological effects of NSAIDs include:
 Analgesic,
 Antipyretic,
 Anti-inflammatory,
 Antiplatelet effects .
B-Acetylsalicylic acid (Aspirin)
It is the prototype of the NSAIDs.
It is the only NSAD that causes irreversible inhibition of both COX-1 and
COX-2.
Its action is dose dependant.
N.B.: Aspirin is available in all forms. Enteric coated aspirin tablets are less
gastric irritant but slow in absorption
1-Therapeutic uses of Aspirin:
 Antipyretic: in feverish conditions.
 Analgesic & Anti-inflammatory: e.g. headache, toothache,
musculoskeletal disorders as rheumatoid arthritis, rheumatic arthritis
and osteoarthritis.
 Anti-platelet: low dose aspirin is used as a prophylaxis against
thrombo-embolism in angina, myocardial infarction, post angioplasty,
atrial arrhythmia, cerebro-vascular diseases, etc…
 Keratolytic (local salicylic acid): removal of warts & corns.
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2-Adverse effects:
 Gastrointestinal irritation : gastritis, gastric erosions, ulcers, bleeding.
 Hypersensitivity: bronchospasm (aggravation of asthma), rhinitis,
nasal polyps, skin rash.
 Bleeding tendency: due to; decrease platelet aggregation &
prothrombin synthesis.
 Renal impairment: analgesic nephropathy(chronic renal failure with
prolonged use), fluid retention.
 Hepatotoxicity.
 Prolonged labor due to inhibition of uterine contraction.
 Reye’s syndrome: rare, fatal sever hepatic injury associated with
encephalopathy. Occurs if aspirin is used in febrile viral infections in
children less than 12 years.
 Salicylism (low grade aspirin toxicity): vertigo, tinnitus, deafness–
often first signs of toxicity.
3-Aspirin overdose (Acute Toxicity):
Extensions of the toxic actions described above, plus at high doses:
 Vasomotor collapse occurs with respiratory,
 Renal failure,
 Hyperpyrexia,
 Dehydration
 Convulsions.
4-Drug-Drug interactions:
 Antagonizes the uricosuric effects of probenecid and the
antihypertensive effect of antihypertensives (e.g. ACE inhibitors, beta
blockers and loop diuretics).
 Increases the plasma concentration of anticoagulants.
5-Other salicylic acid derivatives:
 Non acetylated salicylate ( sodium salicylate, magnesium salicylate )
are less gastric irritants but less effective.
 5-aminosalicylic acid ( mesalamine ) is less absorbed and used for
treatment of inflammatory bowel disease(local action).
 Diflunisal: more potent than aspirin, has little antipyretic action, used
mainly for osteoarthritis.

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C-Other non-steroidal anti-inflammatory drugs:
They may be better tolerated than aspirin.
1-Non selective COX inhibitors:
They inhibit both COX-1 and COX-2 (as aspirin)
 Acetic acid derivatives:

- Carboxylic acetic acid: Indomethacin, Sulindac, Tolmetin
- Phenyl acetic acid: Diclofinac
 Propionic acid derivatives: Ibuprofen, Ketoprofen, Fenoprofen,
Naproxen, Ketorolac.
 Fenamic acid derivatives: Mefenamic acid, Flufenamic acid
 Pyrazolone derivatives: Azapropazone, Phenylbutazone,
Oxyphenobutazone.
 Oxicams: Piroxicam, Meloxicam, Tinoxicam
2-Selective COX-2 inhibitors:
 Celecoxib,
 Rofecoxib
Their primary differences from other conventional NSAIDs are:
- Less gastrointestinal toxicity.
- Less antiplatelet action.
- They have been withdrawn from market because of cardiovascular
risk

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D-Paracetamol (Acetaminophen):
Inhibition of cyclooxygenases in CNS not in peripheral tissues.
2-Pharmacological effects:
 Analgesic,
 Antipyretic
 No significant anti-inflammatory effect.
3-Comparison with Aspirin:
 No antiplatelet action,
 No bronchospasm,
 Gastrointestinal irritation is minimal,
 Not implicated in Reye syndrome.
4-Adverse effects:
 Hepatotoxicity,
 Nephrotoxicity.
5-Paracetamol overdose (Acute Toxicity):
The toxic metabolites increase causing:
 Nausea,
 Vomiting,
 Diarrhea,
 Abdominal pain
 Hepato-renal failure.
6-Management of Paracetamol Overdose:
N-acetylcysteine within the first 12 hours can protect against toxicity.

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III-Drugs used in treatment of gout

Gout is inflammatory arthritis due to deposition of uric acid crystals in the
joint tissue.
Management of Gout differs between acute attacks and chronic phase.
A-Acute attack:
In acute attacks, drug strategy is reduction of the inflammatory process.
1- Colchicine:
 Decreases release of LTB4,
 Decreases leukocyte migration and phagocytosis.
Adverse effects:
 Diarrhea,
 Abdominal pain.
 Prolonged use may cause hematuria, alopecia, myelosuppression and
peripheral neuropathy.
2- Indomethacin and other NSAIDs (Sulindac, Naproxen)
3- Intra-articular steroids.
B-In-between attacks (chronic gout)
Drug strategy is reduction of the uric acid pool.
1-Decrease uric acid synthesis:
 Allopurinol
Inhibits xanthin oxidase enzyme → ↓ uric acid synthesis.

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Adverse effects:
- GIT disturbance,
- Peripheral neuropathy,
- Vasculitis,
- Skin rash.
2-Increase uric acid excretion (uricosuric drugs):
 Probenecid
 Sulfinpyrazone
In large doses, they inhibit proximal tubular reabsorption of urate
(uric acid retention in small dose).
Adverse effects:
- GIT disturbance,
- Nephritic syndrome,
- Skin rash.
They action of uricosuric drugs is antagonized by salicylate .

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Unit II- Drugs affecting renal and

cardiovascular functions

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I-Diuretics
A-Review on Renal physiology:
The kidneys form urine from blood plasma. Blood flow through the kidneys is a
major factor in determining urinary output.
Glomerular filtration is the first step in urine formation. Filtration is not selective
in terms of usefulness of materials; it is selective only in terms of size.
Tubular reabsorption is selective in terms of usefulness. Nutrients such as glucose,
amino acids, and vitamins are reabsorbed from the filtrate in the renal tubules to
the blood in the peritubular capillaries.
Tubular secretion takes place from the blood in the peritubular capillaries to the
filtrate in the renal tubules and can ensure that wastes such as creatinine or excess
H+ ions are actively put into the filtrate to be excreted in urine.
Hormones involved in the formation of urine lead to concentration of the urine:
 Antidiuretic hormone ADH: increase water reabsorption in distal and
collecting tubules.
 Aldosterone: increases sodium reabsorption in the distal tubules and
collecting ducts.
B-Carbonic Anhydrase Inhibitors
 Acetazolamide,
 Dorzolamide
They inhibit Carbonic Anydrase enzyme→ loss of sodium and bicarbonate
in urine→ self-limited alkaline diuresis.

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2-Site of action:
proximal convoluted tubule.
3-Clinical use:
 Glaucoma(↓intraocular pressure),
 Metabolic alkalosis
 Urinary alkalinization.
4-Adverse effects:
 Neuropathy,
 Acidosis,
 Hypokalemia,
 Hyperchloremia.
C-Osmotic diuretics:
 Mannitol (given IV)
↑tubular fluid osmolarity → ↑urine flow.
2-Site of action:
Entire tubule.
3-Clinical use:
 Glaucoma,
 ↓intracranial pressure,
 Acute renal failure.
4-Adverse effects:
 Pulmonary edema,
 Dehydration.
Osmotic diuretics are Contraindicated in Anuria and CHF.

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D-Loop diuretics:
 Furosemide ,
 Bumetanide ,
 Ethacrynic acid
Inhibits Na/K/2CL cotransport system of thick ascending limb of loop of
Henle→↓ Na & CL reabsorption
2-Site of action:
Ascending limb of loop of Henle
3-Clinical use:
 Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary
edema),
 Hypertension,
 Hypercalcemia
4-Adverse effects:
 Ototoxicity
 Allergy
 Hypovolaemia
 Electrolyte disturbance (alkalosis, hypokalaemia, hyponatraemia
hypomagnesaemia, hypocalcaemia),
 Hyperuricaemia
 Hyperglycaemia
E-Thiazides:
 Chlorothiazide,
 Hydrochlorothiazide,
 Indepamide

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They inhibit NaCl reabsorption.
2-Site of action:
Early distal convoluted tubule.
3-Clinical use:
 Edematous states,
 Hypertension,
 Renal calcium stone,
 Nephrogenic diabetes insipidus.
4-Adverse effects:
 Allergy
 Hypovolaemia
 NO ototoxicity
hypomagnesaemia, hypercalcaemia),
 Hyperuricaemia
 Hyperglycaemia
F- K-sparing diuretics:
 Aldosterone receptor antagonist: Spironolactone
 Non-Aldosterone receptor antagonist:
- Triamterene,
- Amiloride
↓ Na reabsorption by:
 Spironolactone: Competitive aldosterone receptor antagonist.
 Triamterene, Amiloride: block Na channels.
2-Site of action:
Collecting tubule

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3-Clinical use:
 K depletion, with other drugs in CHF and Hypertension.
 Spironolactone used in hyperaldosteronism
4-Adverse effects:
 Hyperkalemia,
 Acidosis,
 Spironolactone has anti-androgen effect (e.g. Gynecomastia)
G-Acidifying Salts:
 Ammonium chloride
It causes acidification of urine with excretion of NaCl in urine→ diuresis.

2-Clinical use:
Used to acidify urine & in treatment of alkalosis.

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II-Drugs used in the treatment of congestive heart

failure (CHF)
Heart failure is a condition in which cardiac output is less than the body
needs.
Drugs used in the treatment of CHF are positive Inotropic drugs,
cardioglycosids, diuretics and Vasodilators
A-Cardiac Glycosides:
Digitoxin Digoxin Ouabain
Oral more less 0
bioavailability
Duration of longer shorter shortest
action
Rout of hepatic (so, preferred in renal renal renal
elimination impairment)
Administration oral oral, IV IV
They increase free Ca concentration within the cardiac cells→↑ contractility.
2-Clinical use:
 Heart failure (digitoxin or digoxin in chronic HF & ouabain or
digoxin in acute cases),
 Supraventricular arrhythmia
3-Adverse & toxic effects:
 Nausea,
 Vomiting,
 Diarrhea.
 Blurry yellow vision,
 Arrhythmias.
4-Toxicities of digoxin are increased by:

 Renal failure,

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 Hypokalemia,
 Hypomagnesaemia,
 Hypocalcaemia
 Drug Interaction with quinidine, verapamil, sympathomimetics and
some antibiotics(e.g., erythromycin) .
5-Specific Antidote:
Anti-digitalis Fab fragments
6-Management of toxicity:
 Slowly normalize K+,
 Lidocaine,
 Cardiac pacer,
 Anti-dig Fab fragments.
B-Other Inotropic drugs:
1-β1 agonist:
 Dobutamine, used in acute heart failure (IV drip.).
 Prenalterol, used in chronic heart failure (oral).
 Dopamine, used in resistant heart failure & cardiogenic shock (IV
drip.).
They Stimulate β1 receptors in the heart→↑ contractility.
2-Phosphodiestrase inhibitors (PDE inhibitors):
 Bibpyridines used in for short term treatment of H.F (IV).
- Amrinone
- Milrinone)
 Methylxanthines (Aminophylline) used in acute H.F. with pulmonary
edema ( slow IV)
Mechanism of action :
Inhibit PDE→↑cAMP→↑ contractility.

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C) Vasodilators:
 Angiotensin converting enzyme inhibitors:
- Captopril ,
- Enalapril ,
- Lisinopril
 Calcium channel blockers:
- Amlodipine
 Other vasodilators:
- Hydralazine ,
- Nitroprusside
↓ Peripheral resistance→ ↓ after load→ ↑Cardiac output.
D-Diuretics:
↓ Blood volume→ ↓ venous return→ ↓ preload→ ↑Cardiac output.

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III-Drugs used in the treatment of Arrhythmia

A-Cardiac electro-physiology:
Myocardial action potential and ionic movement occur in atrial and
ventricular myocytes and Purkinje fibers.
 Phase 0 = rapid depolarization; voltage-gated Na channels open
(rapid Na influx).
 Phase 1 = initial repolarization; voltage-gated K channels begin to
open
(K efflux).
 Phase 2 = “plateau” sustained depolarization; voltage-gated Ca

channels open (slow Ca influx).
 Phase 3 = rapid repolarization; voltage-gated slow K channels open
(rapid K efflux).
 Phase 4 = gradual return to resting potential; Na leaves the cell in
exchange with K.

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1-The Heartbeat:
The electrical impulse that triggers a normal cardiac contraction originates at
regular intervals in the sinoatrial node (SAN), usually at a frequency of 60–
100 beats per minute.
This impulse spreads rapidly through the atria and enters the atrioventricular
node (AVN), which is normally the only conduction pathway between the
atria and ventricles.
Conduction through the atrioventricular node is slow, requiring about 0.15 s.
(This delay provides time for atrial contraction to propel blood into the
ventricles.) The impulse then propagates over the His-Purkinje system and
invades all parts of the ventricles. Ventricular activation is complete in less
than 0.1 s; therefore, contraction of all of the ventricular muscle is
synchronous and hemodynamically effective.
2-Control of the SA Node and AV Node.
Both the SA and the AV node are controlled by the autonomic nervous
system.
Parasympathetic stimulation, supplied by the vagus nerve tends to decrease
both the rate and force of contraction of the heart.
Sympathetic stimulation, serves to increase both the rate and force of
contraction of the heart. The predominant sympathetic receptor is a beta-
receptor although it has been shown that a small amount of alpha-receptors
are present in the heart.

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B-Definition and Classification of arrhythmia:
Arrhythmia is a term that is used to refer to any abnormal heartbeat
(Disorders of impulse formation, impulse conduction, or a combination)
1-Classification:
 Tachyarrhythmia:
- Supraventricular :
o Supraventricular tachycardia.
o Atrial flutter.
o Atrial fibrillation (AF)
- Ventricular arrhythmia:
o Ventricular tachycardia
o Ventricular flutter
o Ventricular fibrillation
 Bradyarrhythmia :
- Sinus bradycardia.
- Nodal rhythm.
- Heart block (partial & complete).
C-Antiarrhythmic drugs
The general mechanism of action for all these drugs is to suppress abnormal
beats or restore normal cardiac rhythm by depressing various properties of
the myocardium.
1- Class I (Na+ channel blockers):
They decrease the rate of rise of phase 0 of the action potential decrease
amplitude of action potential.
According to duration of action potential they are subclassified into:

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 Class IA
- Quinidine ,
- Procainamide ,
- Disopyramide
They increase action potential duration, increase refractory period.
Adverse effects:
- Quinidine: cinchonism (headache, tinnitus, deafness, visual
disturbances), thrombocytopenia, hypotension, nausea,
vomiting.
- Procainamide: SLE-like syndrome
- Disopyramide: heart failure.
 Class IB
- Lidocaine IV
- Phenytoin
They decrease action potential duration.
Adverse effects:
- Lidocaine: local anesthetic, CNS stimulation/depression,
hypotension and myocardial depression.
 Class IC
- Flecainide ,
- Encainide
No effect on action potential duration.
Adverse effects:
High potential for proarrhythmia (new arrhythmias).
2- Class II (β blockers)
 Propranolol ,
 Atenolol ,
 Sotalol
They suppress abnormal pacemakers by reducing the slope of spontaneous

depolarization (phase 4). Decrease SAN and AVN activity.

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Adverse effects:
- Impotence,
- Exacerbation of asthma,
- CV effects (bradycardia, AV block, CHF), CNS effects (sedation,
sleep alterations).
- They may mask the signs of hypoglycemia.
3- Class III (K+ channel blockers)
 Amiodarone ,
 Bretylium,
 Sotalol
Adverse effects:
- Amiodarone: pulmonary ﬁbrosis, corneal deposits, thyroid
dysfunction.
- Bretylium : new arrhythmias, hypotension.
- Sotalol: excessive β block.
4- Class IV (Ca2+ channel blockers)
 Verapamil
 Diltiazem.
They slow conduction velocity of atrioventricular node.
Adverse effects:
- Constipation,
- Flushing,
- Edema,
- CV effects (CHF, AV block, sinus node depression)
5- Unclassified
 Adenosine: slow conduction in accessory conducting pathway.
 Digoxin: slow conduction of atrioventricular node.
 Atropine: muscarinic blocking action.
 Adrenaline & Isoprenaline: sympathomimitic action.

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D-Therapeutic indication of antiarrhythemic:
1- Supraventricular tachyarrhythmia:
 Class IV,
 Adenosine,
 Digoxin
2- Ventricular tachyarrhythmia:
 Class IB
3- Supraventricular &Ventricular tachyarrhythmia:

 Class IA,
 Class IC,
 Class II,
 Class III
4- Bradyarrhythmia:
 Atropine,
 Adrenaline
 Isoprenaline

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IV-Drugs used in treatment of angina

Angina pectoris is an acute chest pain that occurs when coronary blood flow
is inadequate to supply the oxygen required by the heart.
A-Types of angina:
 Classic angina(angina of effort or exercise): is due to coronary
atherosclerotic occlusion
 Vasospastic or variant (Prinzmetal) angina: is due to a reversible
decrease in coronary blood flow.
 Unstable angina (crescendo): presents as an acute coronary syndrome
with platelet aggregation.
B-Drug strategies in classic and vasospastic angina:
 O2 requirements
 O2 supply
1-During the acute attack:
 Short acting Nitrates :
- Glyceryl Trinitrate (Nitroglycerin) (sublingual, I.V. Infusion)
- Amyl nitrite (Inhalation)
- Isosorbide dinitrate (Sublingual)
2-In between the attacks:
 Long acting Nitrates
- Isosorbide mononitrate -oral-
- Isosorbide dinitrate (Oral )
 Beta adrenergic blockers
 Calcium channel blockers
 Antiplatelets e.g. (aspirin, dipyridamol): used to  incidence of
coronary thrombosis.

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Drug strategies Nitrates Calcium Beta blockers

channel
blockers
cardiac O2 venodilatation heart rate, force of contraction
requirements peripheral venous return and cardiac output
arteriodilataion
arteriodilataion peripheral
peripheral vascular vascular resistance
resistance
cardiac O2 supply Coronary vasodilatation
Adverse effects of Nitrates:

The major acute toxicities of organic nitrates are direct extensions of
therapeutic vasodilatation:
- Orthostatic hypotension,
- Tachycardia
- Throbbing headache.
Nitrates Tolerance:
Tolerance for the vasodilating action may develop with continuous exposure
to nitrates without interruption.
C-Drug strategies in unstable angina:
 Combination of Nitrates with Beta blockers used initially with
supplemental oxygen.
 To prevent thrombosis (and myocardial infarction): heparin,
warfarine, and antiplatelets.

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V-Antihypertensive drugs
A-Sympathoplegics
1-Centrally acting Alpha 2 agonist:
Methyldopa Clonidine
Mech. Of Activate α2 receptors in the medulla→ ↓central sympathetic
action outflow
Adverse Sedation, dizziness, sexual Sedation, dry mouth , edema,
effects dysfunction, positive severe rebound hypertension
Coombs’ test
Comments Safe in renal dysfunction and
pregnancy
2-Adrenergic neuron blockers:
Reserpine Guanethidine
Mech. of Destruction of storage Binds to storage granules→ inhibit
action granules→ ↓NE NE release
Adverse Sedation, depression, Orthostatic hypotension, fluid
effects diarrhea. retention, sexual dysfunction
,diarrhea
3-Alpha blockers:
 Mech. of action : α1 blocking→ vasodilatation →↓peripheral
resistance
 Selective α1-receptors blockers:
- Prazosin ,
- Terazosin
- Doxazosin.
 Adverse effects:
- First-dose orthostatic hypotension,
- Dizziness,
- Headache.
 Used also in benign prostatic hyperplasia to decrease urinary
retention.

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 N.B. non selective α blockers cause reflex tachycardia; so there use
has diminished after the development of drugs that are relatively
selective for α1-receptors.
4-Beta blockers:
 Mech. of action: β1 blocking→ ↓cardiac output & ↓renin secretion.
 Selectivity:
- Nonselective: propranolol, timolol, pindolol.
- Cardio selective(β1 selective): atenolol, esmolol,metoprolol.
N.B. labetalol (blocks α1 & β receptors-used in
pheochromocytoma)
 Adverse effects :
- Impotence,
- Cardiovascular adverse effects (bradycardia, AV block,
CHF),
- CNS adverse effects (sedation, sleep alterations),
- Non selective drugs may cause exacerbation of asthma.
B-Direct acting vasodilators
Hydralazine Minoxidil Diazoxide Nitroprosside
Mech. of arteriolar dilatation arteriolar dilatation (open K Mixed veno-
action (relax smooth ms. channels in the arterioles) arteriolar dilatation
of arterioles)
Adverse lupus-like Hypertrichosis, Hyperglycemia, Cyanide
effects syndrome, tachycardia, tachycardia, accumulation →
tachycardia, fluid retention fluid retention cyanosis, muscle
fluid retention spasms, psychosis
(with prolonged
therapy),
tachycardia,
fluid retention
Comments Used orally in moderate to severe Used I.V for hypertensive
cases emergencies

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C-Calcium channel blockers (CCBs)
 Mech. of action:
block Ca channels→↓intracellular Ca.
In cardiac muscle→↓contractility→↓cardiac output.
In blood vessels →vasodilatation.
 Selectivity:
- More selective on heart: Verapamil & Diltiazem
- More selective on blood vessels: Nifedipine & Amlodipine
- Constipation ,
- Nausea.
- Heart failure ,
- Heart block (Verapamil & Diltiazem)
tachycardia , flushing (Nifedipine)
D-Drugs affecting angiotensin system
1-Angiotensin converting enzyme inhibitors (ACE Is):
 Captopril
 Enalapril
 Lisinopril
 Mechanism of action:
- Prevent Angiotensin II formation → prevent activation of
AT-1 receptors→ ↓vasoconstriction &↓ aldosterone
secretion→mixed vasodilatation.
- Inhibit the metabolism of bradykinin→vasodilatation.
- Cough,
- Angioedema,
- Proteinuria,
- Taste changes,
- Hypotension,
- Pregnancy problems (fetal renal damage),
- Rash, immune reactions,
- Hyperkalemia.
-

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2-Angiotensin-1 receptors antagonists (AT-1 antagonists):
 Losartan
 Irbesartan
 Candesartan
- Prevent activation of AT-1 receptors→………
 Adverse effects: as ACEIs but without cough .
E-Diuretics:
1-Mechansim of action:
- ↓blood volume→↓cardiac output .
- vasodilator effect: direct effect & by ↓vascular sensitivity to
vasopressor agents → ↓peripheral resistance.
2-Selection:
 Thiazide diuretics: initial therapy in most cases, used in mild to
moderate hypertension.
 Loop diuretics: in sever and malignant hypertension and
hypertension of renal failure.
 K-sparing diuretics: in hyperaldosteronism.
F-Antihypertensive drugs in special cases
Indication Suitable drugs

Angina Beta blockers , CCBs
Heart failure ACE Is , AT-1 antagonists
Diabetes ACE Is , AT-1 antagonists
Dyslipidemias Alpha blockers , CCBs
BPH Alpha blockers

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VI-Drugs used in the treatment of Hyperlipidemia

Hyperlipidemia is a condition of high levels of cholesterol, triglycerides, and
/or lipoprotein in the blood.
Drug Effect on Effect on Effect on Side

LDL “bad HDL “good triglycerides effects/problems
cholesterol” cholesterol”
Bile acid ↓↓ No effect Slight ↑ gastrointestinal
sequestrants upset ,
(Resins) ↓absorbption of
e.g. fat soluble
cholestyramine, vitamins,
colestipol digoxin and
thiazides .
HMG-CoA ↓↓↓ ↑ ↓ gastrointestinal
reductase upset ,
inhibitors myopathy
(Statins) (muscle aches
e.g. lovastatin, and weakness)
pravastatin,
simvastatin,
atorvastatin
Nicotinic acid ↓↓ ↑↑ ↓ gastrointestinal
and its upset , pruritus
derivatives ,facial redness
and flushing
(↓by aspirin or
long-term use)
Lipoprotein ↓ ↑ ↓↓↓ gastrointestinal
lipase upset ,
stimulators myopathy ,
(Fibrates) gallstones,
e.g.
gemfibrozil,
clofibrate

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Antihyperlipidemic agents may prevent cholesterol synthesis or promote the
breakdown of internal cholesterol.
LDL = low density lipoprotein
HDL = high density lipoprotein
HMG-CoA = Hydroxy Methyl Glutaryl -CoA

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Unit III- Drugs acting on the Blood and

Blood Forming Agents

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I-Drugs for iron deficiency anaemia:

A-Physiology:
Iron is required for haemoglobin production. Absence of adequate iron
leads to microcytic hypochromic anaemia (iron deficiency anaemia).
Total body iron: 3.5 gm (2/3 in Hb & 1/3 in ferritin, myoglobin,

haemosidren and enzymes).
 Daily requirement: 10-15 mg of which 10% is absorbed.

 Main dietary source: meat & liver.
Etiology:
 ↓ intake:
- starvation,
- anorexia.
 ↓ absorption:
- gastrectomy,
- malabsorption syndrome and excess phytate, phosphate e.g.
cereals, tannic acid e.g. tea.
 ↑ requirements:
- pregnancy,
- lactation,
- after hemorrhage.
 ↑ loss:
- chronic blood loss (e.g. ankylostoma, chronic GIT bleeding)
B-Iron therapy:
1-Oral iron (Iron salts):
 Ferrous sulfate,
 Ferrous gluconate,
 Ferrous succinate
 Ferrous fumarate.

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They should be in ferrous form (ferric form is unabsorbable)
Duration of treatment should be 3-6 months to replenish iron store.
Side effects:
- Nausea,
- Vomiting,
- Epigastric discomfort,
- Abdominal cramps with diarrhea or constipation,
- Black staining of the teeth & stool.
2-Parenteral iron:
 Iron dextran complex,
 Iron sorbitol
They are indicated if patient not tolerated or not absorbing the oral iron.
Side effects:
- Local pain
- Brownish discoloration of the tissue at site of injection,
- Fever,
- Headache,
- Arthralgia,
- Anaphylactic shock
Antidote for toxicity:Desferoxamine.

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II-Drugs for Megaloblastic anaemia:

A-Physiology:
Vitamin B12 and folic acid are essential for normal DNA synthesis.
Deficiency of either of them results in impaired production and abnormal
maturation of erythroid precursor cells, giving rise to megaloblastic anaemia.
Vitamin B12 deficiency due to a lack of gastric intrinsic factor results in
pernicious anemia. This type of megaloblastic anaemia causes neurological
damage if it is not treated.
Daily requirement:
 B12 → 1 mcgm,
 Folic acid → 1 mg
Main dietary source:
 B12 → animal products,
 Folic acid → vegetables
B-Aetiology:
B12 deficiency Folic acid deficiency

↓ intake Vegetarians, Lack of vegetable intake,
starvation, anorexia starvation, anorexia
↓ absorption Gastrectomy, pernicious malabsorption syndrome,
anemia(absent intrinsic drugs: anticonvulsant e.g.
factor), malabsorption barbitone, folic antagonists e.g.
syndrome methotrxate
↓ utilization Lack of transcbalamin II Methotrexate, trimethprim
↑ requirements pregnancy, lactation pregnancy, lactation, hemolytic
anemia, hemodialysis

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C-Vitamin B12 therapy:
It is given parenteral.
 Cyanocobalamine,
 Hydroxycobalamine
D-Folic acid therapy:

 Folic acid (Oral),
 Folinic acid (Parenteral).
Treatment of Vitamin B12 deficient megaloblastic anemia with folic acid
alone may improve the symptoms; however, neurological damage may still
occur if vitamin B12 intake is not supplemented.

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III- Anti-coagulants for Homeostasis

Homeostasis involves the interplay of three phases (vascular, platelet, and
coagulation).
The end result of these phases are, vasoconstriction, platelets aggregation )
platelet plug) at site of injury, and formation of fibrin clot (coagulation) to
prevent blood loss.
The fibrinolytic system prevents propagation of clotting beyond the site of
vascular injury and is involved in clot dissolution, or lysis.
A-Mechanism of Platelets aggregation :
 Platelet adhesion to site of vascular injury.
 Platelet activation by collagen, ADP, thrombin, TXA2, 5HT →
increase expression of glycoprotein IIb/IIIa receptors on platelets
surface.
 Platelets aggregation by a cross-linking reaction due to fibrinogen
binding to glycoprotein IIb/IIIa receptors.

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B-Mechanism of blood coagulation:

Blood coagulates by the transformation of soluble fibrinogen into insoluble
fibrin.
Several circulating proteins interact in a cascading series of limited
proteolytic reactions.
At each step, a clotting factor (e.g., factor VII becomes an active protease
(e.g., factor VIIa) and activates the next clotting factor until finally a solid
fibrin clot is formed.
This process occurs in two interrelated pathways, the intrinsic (inside blood
vessels) and extrinsic (inside tissues); both converge on a common pathway
that leads to the activation of factor X.
Several of the bloods clotting factors are targets for drug therapy.

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C-Anti-coagulant drugs:
They are drugs which inhibit the development and enlargement of clots by
actions on the coagulation phase.
They do not lyse clots or affect the fibrinolytic pathways.
1-Heparin and LMWH:
 Standard heparin: a mixture of sulphated polysaccharides.

 Low-molecular-weight heparins (LMWH)
- Enoxaparin,
- Dalteparin,
- Ardeparin,
- Tinzaparin:

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They have better bioavailability, longer half-life, less
thrombocytopenia and greater factor Xa specificity than standard
heparin.
They can be administered subcutaneously and without laboratory
monitoring.
 Danaproid: a heparin of different structure. It has greater factor Xa
specificity than LMWH . Bleeding due to it is not reversed by
protamine. It may be safer in hypersensitivity to heparin.
2-Oral Anti-coagulants
 Coumarins (warfarin)
 Drug interaction with oral anticoagulants:
- Actions increased by aspirin, cimetidine, metronidazole,
sulfonamides.
- Actions decreased by vitamin K, barbiturates, carbamazepine,
cholystramine, rifampin, thiazides
Heparins Warfarin
(oral anticoagulants)
Chemical Large water-soluble Small lipid-soluble molecule
nature polysaccharide
Rout of Parenteral (IV, SC) Oral
administration
Site of action Blood Liver
Onset of Rapid (seconds) Slow, limited by half-lives of
action normal clotting factors
Mechanism of Activates antithrombin III, Impairs the hepatic synthesis
action resulting in the inactivation of vitamin. K–dependent
of several clotting factors clotting factors II, VII, IX,
(especially IIa & Xa). and X (vitamin K
Action in vivo & in vitro. antagonist). Action in vivo
only.
Duration of Acute (hours) Chronic (weeks or months)
action
Clinical use Rapid anticoagulation Long-term anticoagulation
(intensive) for thromboses, (controlled) for ……
emboli, stroke, angina, Not used in pregnant women

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Myocardial Infarction, (can cross the placenta).
DVT. Used during
pregnancy (does not cross
placenta)
Monitoring Partial thromboplastin time Prothrombin time PT
PTT (intrinsic pathway) (extrinsic pathway)
Toxicity Bleeding, Bleeding, teratogenic, drug–
thrombocytopenia, drug interactions
hypersensitivity,
osteoporosis.
Antagonist Protamine sulfate IV vitamin K and fresh
frozen plasma
D-Fibrinolytic drugs
They are also called thrombolytics, drugs which dissolve the thrombus by
formation of the fibrinolytic plasmin from plasminogen.
1-Non-Fibrin selective (Non selective fibrinolytics):
 Urokinase.
 Streptokinase.
 Anistreplase (Anisooylated plasminogen streptokinase activator
complex (APSAC) ).
They Act on both fibrin-bound and free(circulating)plasminogen →
fibrinolysis →dissolve the thrombus,
systemic fibrinogenolysis →generalized hypo-coagulabiliy state .
2-Fibrin selective (Selective fibrinolytics):
 Recombinant human tissue-type plasminogen activator (rt-PA):
- Alteplase,
- Reteplase,
- Tenecteplase

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 Recombinant single chain urokinase plasminogen activator (rscu-PA).
They Act mainly on fibrin-bound plasminogen → fibrinolysis →dissolve
the thrombus
They are less liable to cause coagulation disturbance.

3-Clinical uses of fibrinolytic drugs:
 Coronary artery thrombosis in myocardial infarction: they decrease
mortality by >60% if used within 3 hours.
 Non coronary thrombosis:
- Deep venous thrombosis,
- Pulmonary embolism,
- Occular thrombosis.
4-Side effects of fibrinolytic drugs:
 Bleeding,
 Hypersensitivity reaction (streptokinase & APSAC)
5-Antidote in excessive bleeding:
Antifibrinolysins
 Aminocaproic acid
 Tranxamic acid

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E-Anti-platelet drugs
They are drugs which inhibit platelet aggregation and so, inhibit the clot
formation.
1-Aspirin:
The prototype anti-platelet drug.
It irreversibly inhibits COX in platelets→↓ TXA2 →↓activation,
2-ADP receptor blockers:

 Ticlopidine
 Clopidogrel:
They block ADP receptors on platelets→ ↓activation,
Ticlopidine has risk of causing sever thrombocytopenia & neutropenia
3-Antagonists of Glycoprotein IIb/IIIa:
 Abciximab,
 Eptifibatide,
 Tirofiban:
They are antagonists that bind to glycoprotein IIb/IIIa receptors→
↓aggregation by preventing cross-linking reaction.
4-Dipyridamole:
Inhibition of PDE →↑cAMP in platelets→ ↓aggregation
N.B.: largely ineffective when used alone

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5-Clinical uses of anti-platelet drugs:

As a prophylaxis against:
 Thrombo-embolism in angina,
 Myocardial infarction,
 Post angioplasty,
 Atrial arrhythmia,
 Cerebro-vascular diseases, etc…
F-Fibrinolytic inhibitors (Antifibrinolytics)
 Tranexamic acid.
 Aminocaproic acid.
They are drugs which inhibit fibrinolysis by inhibition of plasminogen
activation.
Clinical uses:
 Antidote for fibrinolytic drugs.
 Control bleeding following surgery.
 Hemophiliac patients, to control bleeding after minor trauma or
surgery.

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Unit IV- Drugs used in Gastro-

Intestinal diseases

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I-Gastric secretion
A-Regulation of acid secretion:
Phases of acid secretion in response to food:
1-Cephalic Phase 2-Gastric Phase 3-Intestinal
Phase
Stimulant Psychic e.g. smell, Food in stomach Acid chime in
taste, sight, or (antral the duodenum
discussion of food distention)
Mediated Acetylcholine (Vagus Gastrin hormone Entrogastrone
through nerve) hormone
Effect on acid ↑↑↑ ↑↑↑ ↓↓↓
secretion
B-Role of acetylcholine, histamine and gastrin:

Acetylcholine and Gastrin stimulate the enterochromaffin-like (ECL) cells to
release histamine.
The parietal cell contains receptors for acetylcholine(M3), histamine(H2)
and gastrin. When they bind to the parietal cell receptors, they stimulate acid
(hydrogen ion) secretion by the H /K ATPase (the proton pump) on the
canalicular surface.

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II-Drugs used in treatment of gastric ulcer:

A-H2-receptor antagonists:
 Cimetidine,
 Ranitidine,
 Nizatidine
 Famotidine
They inhibit basal and meal-stimulated gastric acid secretion.
Cimetidine is less potent and has more adverse effects than the other drugs.
2-Adverse effects:
Cimetidine rarely produces side effects such as mental status changes
(confusion, hallucinations, agitation) and antiandrogenic effects
(gynecomastia, decreased libido or impotence in men and galactorrhea in
women).

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3-Drug Interactions:
 Cimetidine inhibits activity of hepatic enzyme cytochrome P450 
decrease metabolism of other drugs such as warfarin, phenytoin,
several benzodiazepines, ß-blockers, Ca channel blockers, tricyclic
antidepressants, metronidazole, etc.
 Unlike cimetidine, its newer and more potent congeners, ranitidine,
nizatidine, and famotidine, have no antiandrogenic effects and do not
interfere with the hepatic biotransformation of other drugs.
B-Proton pump (H /K ATPase) inhibitors:
 Omeprazole,
 Lansoprazole,
 Pantoprazole,
 Rabeprazole
 Esomeprazole
They totally block basal and meal-stimulated gastric acid secretion (more
effective than H2-receptore antagonists in inhibition of acid secretion)
2-Adverse effects:
 GI disturbance (indigestion, diarrhea and colic).
 Enteric infections (eg,salmonella, shigella) from ingestion of bacteria
due to decrease acidity.
 Gastric carcinoid tumors have developed in rats but not in human after
long-term use.
 Decrease absorption of vit B12 and minerals (iron, calcium, zinc)
from food due to decrease acidity.
 They decrease absorption of drugs for which gastric acidity affects
bioavailability e.g. digoxin, quinolones, ketaconazole.
 Omeprazole decrease activity of cytochrome P450 decrease
metabolism of warfarin, phenytoin and diazepam.

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C-Antacids:
 Absorbable:
- NaHCO3
 Non-absorbable:
- CaCO3,
- Al(OH) 3,
- Mg salts (e.g. Mg(OH)2 and Mg trisilicate)
1-Mechanism of Action:
They neutralize gastric acidity.

2-Adverse effects:
They can affect absorption, bioavailability, or urinary excretion of other
drugs by altering gastric and urinary pH or by delaying gastric emptying.
Hence, antacids should not be given within 2 hours of doses of tetracyclines,
digoxin, quinolones and ketaconazole.
Overuse can also cause the following problems:
 Sodium bicarbonate NaHCO3:
- Alkalosis,
- Rebound hyperacidity.
 Calcium carbonate CaCO3:
- Constipation,
- Hypercalcemia
 Aluminum hydroxide Al(OH) 3:
- Constipation
- Hypophosphatemia .
 Magnesium salts:
- Diarrhea
- Hypermagnesemia
 All can cause hypokalemia

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D-Drugs that protect mucosa
1-Sucralfate (Aluminum sucrose sulfate)
Action:
It polymerizes in the acid environment of the stomach and selectively binds
necrotic peptic ulcer tissue, creating a protective layer against acid and
pepsin.
Adverse effects:
- It may cause constipation due to the aluminum salt.
- It may bind to other medications, impairing their absorption
(e.g. tetracyclines, digoxin, quinolones and ketaconazole).
2-Prostaglandin Analogs: Misoprostol

Misoprostol is PGE1 analog. It increases production and secretion of gastric
mucous barrier.
Adverse effects: Diarrhea.
It is contraindicated in women of childbearing potential (abortifacient).
3-Colloidal Bismuth Compounds:

 Bismuth subsalicylate
 Bismuth subcitrate
 Bismuth dinitrate
Mechanism of Action:
- Like sucralfate, it coats ulcers and erosions, creating a protective layer
against acid and pepsin.
- It may also stimulate prostaglandin, mucus, and bicarbonate secretion.
- Bismuth has direct antimicrobial activity against H pylori.
Adverse effects: blackening of the tongue and stool.

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Prolonged usage may rarely lead to bismuth toxicity resulting in
encephalopathy (headaches, confusion, seizures).
4-Carbenoxolone:
It is a derivative of glycyrrhetinic acid, which occurs in the sap of licorice
root. It stimulates prostaglandin and mucus secretion (aldosteron like
action).
Adverse effects:
Hypokalemia and Na retention (aldosteron like effect)  oedema and

hypertension.

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III-Drugs used to eradicate Helicobacter pylori bacteria

This microorganism plays an important role in the pathogenesis of
chronic gastritis and peptic ulcer disease.
Triple therapy: four times daily for 14 days
1- Bismuth subsalicylate (524 mg)
2- Tetracycline (500 mg)
3- Metronidazole (250 mg)
Because of the need for four-times daily dosing and the high side
effect profile, this regimen is no longer used as first-line therapy for H
pylori eradication.
New triple therapy: twice daily for 10–14 days
1- A proton pump inhibitor
2- Clarithromycin (500 mg)
3- Amoxicillin (1 g)
For patients who are allergic to penicillin, metronidazole (500 mg)
twice daily should be substituted for amoxicillin.
After completion of triple therapy, the proton pump inhibitor should
be continued once daily for a total of 4–6 weeks to ensure complete
ulcer healing.

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IV-Vomiting
A-Emetics
They are agents that induced reflex vomiting.
They are used in emptying the stomach in awake patients who have ingested
a toxic substance or have recently taken a drug overdose.
Emesis should not be induced if the patient has central nervous system
depression or has ingested certain volatile hydrocarbons and caustic
substances.
1-Ipecac syrup (alkaloid emetine is the active principal ingredient)
 Action: It acts directly on the CTZ and also indirectly by irritating
the gastric mucosa.
 Adverse effects: Ipecac is cardiotoxic if absorbed and can cause
cardiac conduction disturbances, atrial fibrillation, or fatal
myocarditis. If emesis does not occur, gastric lavage using a
nasogastric tube must be performed.
2-Apomorphine (a derivative of morphine)
 Action: acts directly on the CTZ. It also is more effective if water is
first administered before oral or subcutaneous dosing.
 Adverse effects: Excessive dosage may cause respiratory depression
and circulatory collapse. Opioid antagonists such as naloxone usually
reverse the depressant actions of apomorphine.
B-Antiemetic drugs:
Antiemetics may prevent emesis by blocking the CTZ or by preventing
peripheral or cortical stimulation of the emetic center.
1-H1 antagonists:
 Diphenhydramine
 Dimenhydrinate
 Meclizine
They block H1 receptors in emetic center and vestibular system. They have
also antimuscarinic action.

pharmacology
Clinical Uses:
Most effective in motion sickness and vertigo.
Adverse effects:
Sedation and atropine like side effects e.g. dry mouth, blurred vision, and
urinary retention.
2-Anticholinergics:
 Hyoscine (scopolamine)
They block muscarinic receptors in emetic center and vestibular system and
GIT.
Uses:
Motion sickness and vertigo.
Adverse effects:
Atropine like side effects e.g. dry mouth, blurred vision, and urinary
retention.
3-Serotonin 5-HT3 Antagonists:
 Ondansetron
 Granisetron
 Dolasetron.
Action:
They block 5-HT3 receptors in CTZ and GIT.
Uses:
Chemically induced vomiting e.g. postoperative and cancer chemotherapy.
Adverse effects:
Constipation, headache and flushing.

pharmacology
4-Dopamine receptor blockers:
a. Metoclopramide and domperidone
 Action: block D2 and 5-HT3 receptors in CTZ and GIT.
 Uses: chemically induced vomiting and vomiting of pregnancy
(metoclopramide).
 Adverse effects: hyperprolactinaemia and CNS side effects (see
later).
b. Phenothiazines (e.g. prochlorperazine, promethazine and
thiethylperazine) and Butyrophenones (e.g. droperidol)
 Action: block D2 receptors in CTZ and block peripheral
transmission to emetic center.
 Uses: chemically induced vomiting.
 Adverse effects: hyperprolactinaemia, sedation, extrapyramidal
side effects (e.g. parkinsonism) and hypotension may occur.
5-Cannabinoids: Dronabinol
 Action: block opiate receptors in CTZ and emetic center.
 Uses: chemically induced vomiting not controlled by other
antiemetics.
 Adverse effects: dry mouth, sedation, psychosis, visual
hallucination and addiction
6-Benzodiazepines: Lorazepam or diazepam
 Action: mild antiemetic action may be due to their anxiolytic
and sedative effects.
 Adverse effects: sedation.
7-Corticosteroids: Dexamethasone, methylprednisolone
 Action: may be due to blockade of PGs.
 Adverse effects: see later.
8-Vitamin B6:
 Action: may be due to regulation of GABA (inhibitory CNS
transmitter) /Glutamine (excitatory CNS transmitter) balance.
 Uses: vomiting of pregnancy (drug of choice).

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V-Motility of gastro-intestinal tract (GIT)

A- Purgatives:
They are drugs given to evacuate the bowels.
Laxatives are agents that cause mild purgation.
Cathartics are agents that cause severe purgation.
They are drugs given to evacuate the bowels in the following cases:
 Constipation.
 Drug and food poisoning (Mg SO4).
 Before and after some antihelmentics (Mg SO4).
 Bowel preparation before:
- X-ray on GIT.
- GIT operations.
 To prevent straining in patients with hernia, piles or
cardiovascular disease.
1-Bulk-Forming Purgatives:
 Natural plant products:
- Bran,
- Psyllium,
- Methyl cellulose
 Synthetic fibers
- Polycarbophil
Action:
Indigestible, hydrophilic colloids that absorb water, forming a bulky,
emollient gel that distends the colon and promotes peristalsis
Adverse effects:
Increased bloating and flatus.

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2-Osmotic Purgatives:
 Lactulose,
 Mg sulphate
 Na/Ka tartrate.
Action:
Soluble but non absorbable compounds that increase the osmotic pressure in
the intestinal lumen result in increased stool liquidity due to retention of
water.
Adverse effects:
 Lactulose
- Nausea,
- Vomiting,
- Diarrhea
- Flatulence.
 Mg sulphate
- Hypermagnesemia and Hyperphosphatemia in patient with
renal diseases
 Na salts
- retention of sodium & water
3-Stimulant (irritant) Purgatives (Cathartics):
 Castor oil,
 Diphenylmethane Derivatives
- Phenolphthalein
- Bisacodyl
 Anthraquinone derivatives
- Cascara,
- Aloe
- Senna
- Rhubarb
Action:
They act on the mucosa of the intestine to stimulate peristalsis either by
irritation or by exciting reflexes in the mesenteric plexuses. They also inhibit
water absorption.

pharmacology
According to the site of irritation, castor oil is small bowel irritant but
diphenolmethane and anthraquinone are large bowel irritants.
Adverse effects:
Severe diarrhea which may cause dehydration & electrolyte loss, abdominal
colic and abortion in pregnant female (uterine contraction).
Diphenylmethane derivatives may cause rare but severe allergic reactions.
Chronic use of anthraquinone derivatives leads to a brown pigmentation of
the colon known as “melanosis coli”.
4-Lubricant Purgatives (Stool softeners):
 Mineral oil (Liquid paraffin),

 Docusate
 Glycerin suppository.
Action:
These agents soften stool material, permitting water and lipids to penetrate.
Adverse effects:
Long-term use of liquid paraffin can impair absorption of fat-soluble
vitamins (A, D, E, K) and it can result in a severe lipid pneumonitis if
inhaled into the lungs.
5-Misuse of purgatives:
Chronic use of purgatives may cause laxative habit or dependence due to:
- Loss of spontaneous bowel movements.
- Loss of spontaneous rectal defecation reflex.

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B-Drugs that increase gastrointestinal motility (Prokinetics)
They are drugs that can selectively stimulate gut motor function. They
increase contractile force and accelerate intraluminal transit.
Effects and Uses:
 Agents that increase lower esophageal sphincter pressures may be
useful for Gastroesophageal Reflux Disease (GERD)
 Agents that enhance gastric emptying may be helpful for gastroparesis
and postsurgical gastric emptying delay.
 Agents that enhance small intestine emptying may be beneficial for
postoperative ileus or chronic intestinal pseudo-obstruction.
1-Cholinomimetic agents :
 Bethanechol
 Neostigmine
Action:
- Bethanechol : direct agonist at muscarinic M3 receptors on muscle
cells and at myenteric plexus synapses.
- Neostigmine: acetylcholinesterase inhibitor.
Adverse effects:
Cholinergic side effects include excessive salivation, nausea, vomiting,
diarrhea, and bradycardia.
2-Cisapride and Tegaserod:
They are serotonin-4 (5-HT4) receptor agonist on enteric neurons, which
promotes release of acetylcholine from the myentric plexus.
Adverse Effects:
Due to prokinetic effects in the colon, abdominal cramps and diarrhea may
occur.
In addition, cisapride rarely lead to serious cardiac arrhythmias.

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3-Metoclopramide and Domperidone :
They are dopamine D2 receptor antagonists potentiate cholinergic smooth

muscle stimulation (D2 receptors in GIT) and potent antiemetic action (D2
receptors in the chemoreceptor trigger zone of the medulla).
They have also agonist activity at serotonin-4 (5-HT4) receptors.
Adverse Effects:
Elevated prolactin levels (hyperprolactinaemia) can cause galactorrhea,
gynecomastia, impotence, and menstrual disorders.
- Metoclopramide: The most common adverse effects involve the
central nervous system (restlessness, drowsiness, insomnia, anxiety)
and extrapyramidal effects (dystonias, akathisia, parkinsonian
features) due to central dopamine receptor blockade. For this reason,
long-term use should be avoided.
- Domperidone: is extremely well tolerated. Because it does not cross
the blood-brain barrier to a significant degree, neuropsychiatric and
extrapyramidal side effects are rare.
4-Macrolide antibiotics : Erythromycin
They directly stimulate motilin receptors on gastrointestinal smooth muscles.
Intravenous erythromycin is beneficial in some patients with gastroparesis;
however, tolerance rapidly develops.
Adverse Effects:
Tachyphylaxis

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C-Antidiarrhoeals:
Antidiarrhoeals agents may be used safely in patients with mild to moderate
acute diarrhea.
However, they should not be used in patients with bloody diarrhea, high
fever, or systemic toxicity because of the risk of worsening the underlying
condition.
They should be discontinued in patients whose diarrhea is worsening despite
therapy.
Antidiarrhoeals are also used to control chronic diarrhea caused by such
conditions as irritable bowel syndrome (IBS) or inflammatory bowel disease
(IBD).
1-Opioid Agonists:
Natural
- Opium tincture containing morphine.
 Synthetic
- Diphenoxylate
- Loperamide.
Activation of opioid receptors in the enteric nerve plexus results in inhibition
of propulsive motor activity and enhancement of segmentation activity.
Adverse Effects:
Central nervous system effects (sedation, respiratory depression, physical
dependence) limit the usefulness of most opioids.
- Loperamide does not cross the blood-brain barrier and has no central
effects (therefore, it is the opioid antidiarrheal of first choice.
- Diphenoxylate at the doses usually employed, has a low incidence of
central opioid actions. Commercial preparations commonly contain
small amounts of atropine to discourage overdosage (by atropine side
effects).
-

pharmacology
2-Adsorbents:
 Kaolin (naturally occurring hydrated magnesium aluminum silicate),
 Pectin (indigestible carbohydrate derived from apples),
 Medicinal charcoal
 Chalk.
Action:
They bind diverse substances, including bacteria, toxins and fluid, thereby
permitting them to be inactivated and eliminated and decrease stool liquidity
and number.
Adverse Effects:
The adsorbents are generally safe, but they may cause constipation and may
interfere with the absorption of some drugs from the GI tract (bind to them)
so; they should not be taken within 2 hours of other medications.
3-Colloidal Bismuth Compounds: Bismuth subsalicylate
It also binds intestinal toxins and may coat irritated mucosal surfaces. It
reduces stool frequency and liquidity due to salicylate inhibition of intestinal
prostaglandin and chloride secretion.
4-Bile Salt Binding Resins:
 Cholestyramine
 Colestipol
They bind bile salts and excrete them in stool.

Clinical Use:
Chronic diarrhea due to bile salt malabsorption.
Adverse Effects:
Bloating, flatulence, constipation, and fecal impaction. They may interfere
with the absorption of some drugs from the GI tract (bind to them) so; they
should not be taken within 2 hours of other medications.

pharmacology
5-Astringents: Tannic acid (home remedy: black tea) or metal salts
They precipitate surface proteins and are thought to help seal the mucosal
epithelium. Although astringents induce constipation, a therapeutic effect in
diarrhea is doubtful.
6-Antibacterial drugs:
Use of these agents (e.g., cotrimoxazole) is only rational when bacteria are
the cause of diarrhea. This is rarely the case.
It should be kept in mind that antibiotics also damage the intestinal flora
which, in turn, can give rise to diarrhea.
7-Oral rehydration solution:

(g/L of boiled water: NaCl 3.5, glucose 20, NaHCO32.5, KCl 1.5)
Oral administration of glucose-containing salt solutions enables fluids to be
absorbed because toxins do not impair the cotransport of Na+ and glucose
(as well as of H2O) through the mucosal epithelium.
In this manner, although frequent discharge of stool is not prevented,
dehydration is successfully corrected.

pharmacology

pharmacology
D-Antispasmodics:
They are drugs used for the relief of the painful biliary, ureteral or colonic
spasms.
1-Anticholinergic drugs:
 Atropine,
 Propantheline,
 Dicyclomine,
 Oxybutynin
 Hyoscine butyl bromide(N-Butylscopolamine).
These drugs inhibit muscarinic cholinergic receptors in the enteric plexus
and on smooth muscle.
Adverse effects:
Anticholinergic side effects including dry mouth, visual disturbances,
urinary retention, and constipation.
2-Other smooth muscle relaxants:
 Papaverine
 Mebeverine
 Nitrites.
Papaverine and mebeverine are more specific on the colon

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VI- Drugs affecting biliary system

A-Antispasmodics:
They are used in cases of biliary colic.
B-Drugs for dissolving gallstones:
Bile acids:
 Chenodeoxycholic acid (CDCA)
 Ursodeoxycholic acid (UDCA).
They decrease the cholesterol content of bile. Thus, cholesterol-containing
stones can be dissolved with long-term oral administration.
UCDA is more effective and better tolerated than is CDCA.
C-Cholekinetics (Cholagogues)
Drugs that stimulate the gallbladder to contract and empty, e.g., egg yolk,
the osmotic laxative MgSO4, and cholecystokinin.
Cholekinetics are employed to test gallbladder function for diagnostic
purposes.

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VII-Other Gastrointestinal Drugs

A-Choleretics:
 Bile acids
 Bile salts
They are supposed to stimulate production and secretion of bile fluid. This
principle has little therapeutic significance.
B-Antiflatulents (Carminatives):
They serve to alleviate meteorism (excessive accumulation of gas in the
gastrointestinal tract).
Defoaming agents, such as dimethicone (dimethylpolysiloxane) and
simethicone, in combination with charcoal, are given orally to promote
separation of gaseous and semisolid contents.
C-Pancreatic enzymes:
From slaughtered animals are used to relieve excretory insufficiency of the
pancreas
( disrupted digestion of fats; steatorrhea).

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Unit V- Chemotherapy of Parasitic

Infections

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I- Anti-protozoal drugs
A-Treatment of Malaria
The malarial parasite is a single-cell protozoan (plasmodium).
Although more than 100 species of plasmodia have been identified, only
four are capable of infecting humans (Plasmodium malariae, P. ovale, P.
vivax, andP. falciparum)
 Drugs classification based on parasite cycle
A. Drugs that kill the parasite in the Pre-erythrocytic stage:

 Used for chemoprophylaxis.
a. Kill the parasite in the liver (Tissue schizonticide):
1. Primaquine. 2. Proguanil
b. Kill the parasite as soon as they reach RBCs:
1. Chloroquine. 2. Proguanil. 3. Fansidar.
B. Drugs that kill the parasite in the Erythrocytic stage (Blood

schizonticide)
 Used for clinical cure (treatment).
1. Chloroquine.
2. Quinine.
3. Mefloquine.
4. Pyrimethamine.
5. Sulfonamide combinations: e.g.
- Fansidar (Sulphadoxine + Pyrimethamine).
C. Drugs that kill the Gametocytes (Gametocide):
 Used for prevention of transmission.
1. Primaquine. 2. Proguanil. 3. Pyrimethamine.
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 Drugs used in malaria

1. Chloroquine
 Mechanism of action: inhibits DNA and RNA synthesis and
inhibits digestion of Hb by the parasite.
 Therapeutic uses:
a. Antimalaria: see the table below.
b. Treatment of amebic liver abscess and giardiasis.
c. Treatment of rheumatoid arthritis and SLE.
 Adverse effects:
a. Visual disturbances.
b. Hypotension and arrhythmia with i.v. injection.
c. Bone marrow depression.
2. Primaquine
 Mechanism of action: produce oxidizing metabolites that
interrupt mitochondrial functions of the parasite.
 Therapeutic uses: Antimalaria; see the table below.
a. Sever hemolytic anemia: in patients with G6P defidiency.
b. Bone marrow depression.
3. Quinine
 Mechanism of action: inhibit DNA and protein synthesis.
a. Cinchonism: ringing in ears, blurred vision, sweating,
nausea.
b. Syncope and arrhythmia.
c. Blackwater fever: massive hemolysis with fever, dark urine
and renal failure.
d. Neurotoxicity.
4. Mefloquine
 Mechanism of action: unknown.
 Therapeutic uses: Antimalaria
 Adverse effects: neurotoxicity: headache, vertigo, psychosis.

pharmacology
5. Antifolate drugs: Pyrimethamine, Proguanil, Fansidar
 Mechanism of action: inhibit folic acid synthesis→ inhibit
DNA synthesis.
 Therapeutic uses: Antimalaria;
Plasmodial strain Drug of choice
P. malariae and chloroquine-sensetive P. falciparum
 Prophylaxis and treatment (cure) Chloroquine
P. vivax, P. ovale
 Prophylaxis Chloroquine
 Treatment (cure) Chloroquine + Primaquine
(To prevent relapses i.e. radical cure).
Chloroquine-resistant P. falciparum
 Prophylaxis Chloroquine +
proguanil or fansidar or doxycycline
 Treatment (cure) 1. Quinidine +

fansidar or a tetracycline
Or 2. Mefloquine alone.

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pharmacology
B-Treatment of Amoebiasis
Amoebiasisis caused by the protozoan Entamoeba histolytica.
 Classification of drugs
A. Luminal amoebicides:
 They are active only against the cysts present in the lumen of
intestine.
1. Diloxanide.
2. Iodoquinol
3. Antibiotics:
a. Erythromycin and paromomycin: are directly amebicidal.
b. Tetracyclines: act indirectly by inhibiting the bactrial
flora on which E.histolytica depend for its nutrition.
B. Systemic (Tissue) amoebicides:
 They
are active only against the invasive trophozoites in
tissues (intestinal wall, liver, and lung) but are ineffective
against the cysts in the intestinal lumen
1. Emetine and dehydroemetine.
2. Chloroquine (active against liver amoebiasis only).
C. Mixed amoebicides:
 They are active against both intestinal and tissue forms.
 Nitroimidazoles: e.g. metronidazole, tinidazole.
 Drugs used in amoebiasis
1. Diloxanide furoate
 Mechanism of action: Unknown
 Therapeutic uses: Antiamoebic; see the table below.
 Adverse effects: nausea, diarrhea, abdominal discomfort.
2. Iodoquinol
a. Antiamoebic; see the table below.
b. Balantidiasis (Balantidium coli) and giardiasis(Giardia
lamblia).
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a. Diarrhea, abdominal discomfort.
b. Thyroid enlargement.
c. eurotoxicity (optic atrophy, peripheral neuropathy).
3. Emetine and dehydroemetine
 Mechanism of action: block protein synthesis.
a. Direct myocardial depression, syncope.
b. Nausea, vomiting, and abdominal discomfort.
4. Chloroquine:
5. Metronidazole
 Mechanism of action: Inhibits DNA replication
a. Antiamoebic; see the table below.
b. Balantidiasis, giardiasis, and trichomoniasis (Trichomonas
vaginalis).
c. Dracunculiasis (Dracunculus medinensis) (medina worm)
(guinea worm)
d. Anaerobic infections: e.g. cancrum oris, peritonitis,
puerperal sepsis, etc.
a. GIT: nausea, vomiting, metallic taste, and hepatotoxicity.
b. CNS: vertigo, dizziness, convulsions
c. Mutagenicity and carcinogenicity (with prolonged use).
d. Dark brown urine.
 N.B. other nitroimidazoles have similar effects as
mitronidazole with longer duration of action.

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Amebiasis Drug of choice Comments
1st 2nd
Asymptomatic and Diloxanide furoate Iodoquinol

mild intestinal
infection
Moderate to severe Metronidazole + Paromomycin + Iodoquinol can be substituted

intestinal infection for diloxanide furoate.
(amebic dysentery) diloxanide furoate diloxanide furoate
Systemic amebiasis Metronidazole + Chloroquine + Although effective, emetine

and dehydroemetine are not
diloxanide furoate diloxanide furoate recommended because of
potential toxicity.
C-Treatment of Trichomoniasis and Giardiasis

Trichomoniasis:
It is caused by the protozoan Trichomonas vaginalis.

 Drugs of choice for treatment: Metronidazole, Tinidazole
 Relapses occur if the infected person’s sexual partner is not treated
simultaneously
.Giardiasis:
 It is caused by the protozoan Giardia lamblia.

 Drugs of choice for treatment: as trichomoniasis.
 Treatment of Trypanosomiasis
1. Nifurtimox
 Mechanism of action: generation of toxic oxygen radicals.
 Therapeutic uses: south american trypanosomiasis (Chagas' disease).
 Adverse effects: nausea, vomiting, abdominal pain, skin rashes,
headache.
2. Suramin
 Therapeutic uses: african trypanosomiasis (sleeping sickness).

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 Adverse effects: acute reaction in sensitive individuals results in
nausea, vomiting, colic, hypotension, urticaria, and even
unconsciousness
3. Pentamidine isethionate
 Mechanism of action: inhibit DNA replication and function.
a. African trypanosomiasis (sleeping sickness).
b. Visceral leishmaniasis (kala azar) as an alternative to antimonials.
 Adverse effects: tachycardia, vomiting, shortness of breath, headache,
a fall in blood pressure, and changes in blood sugar (hypoglycemia or
hyperglycemia).
4. Eflornithine
 Mechanism of action: inhibits cell division, differentiation.
 Adverse effects: anemia and leukopenia.
5. Arsenicals: e.g. Melarsoprol
 Mechanism of action: affecting cellular structure and function.
 Therapeutic uses: african trypanosomiasis (sleeping sickness)
 Adverse effects: vomiting, abdominal cramps, fever, rashes, peripheral
neuropathy, most frequently adverse effect is encephalopathy.

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Trypanosomiasis Drug of choice
1st 2nd
Trypanosoma cruzi; it causes:
South American
trypanosomiasis
Nifurtimox
(Chagas' disease)
T. brucei; it causes:
African trypanosomiasis
(sleeping sickness)
a. Early stage Suramin (i.v.) + Pentamidine isethionate (i.m.)
(no CNS involvement) or
Eflornithine
b. Late stage Melarsoprol (Arsenicals) Eflornithine
(CNS involvement) or
Suramin followed by melarsoprol

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D-Treatment of Leishmaniasis
Antimonials: e.g. Stibogluconate
 Mechanism of action: inhibits the production of energy derived from
anaerobic metabolism.
 Therapeutic uses: leishmaniasis
 Adverse effects: coughing, myalgia, arthralgia, rashes, abdominal pain,
diarrhea, and anaphylactoid collapse, and pancreatitis.
Leishmaniasis Drug of choice
1st 2nd
Leishmania braziliensis and L. mexicana ; they cause:
American mucocutaneous leishmaniasis Stibogluconate Amphotericin B

(antimonials)
L. donovani ; it causes:
Visceral leishmaniasis Stibogluconate Pentamidine

(antimonials) isethionate
(kala azar)
L. tropica & L. major ; they cause:
Cutaneous leishmaniasis (oriental sore) Stibogluconate

(antimonials)

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II-Anti-helmintic drugs
 Different helminth (metazoan) infection
Nematode (Round worm) Infections Cestode (Tape worm) Trematode (Flukes) Infections
(Flat worm) Infecti ons
A. Intestinal nematodes 1. Taenia saginata (Beef A. Bl ood Fluke Infecti ons
1. Ascaris lumbricoides tapeworm) (Schistosomi asis)
2. Ancylstoma duodenale (Hookworm) 2. Taenia solium (Pork tapeworm) a. Schistosoma hematobium
3. Enterobius vermicularis (Oxyuris) 3. Diphyllobothrium latum (Fish b. Schistosoma mansoni
(Pinworm) tapeworm) c. Schistosoma japonicum
4. Trichuris trichiura (Whipworm) 4. Hymenolepis nana (Dwarf
5. Strongyloides stercoralis tapeworm) B. Intestinal Fluke Infecti ons
5. Echinococcus granulosus and a. Heterophyes heterophyes
B. Tissue nematodes Echinococcus multilocularis
1. Filaria worms (Wuchereria bancrofti, (Hydatid disease) b. Fasciolopsis buski
Brugia malayi, Loa loa ) c. Metagonimus yokogawai
2. Dracunculus medinensis (Medina worm)
(Guinea worm) C. Li ver Fluke Infections
3. Larva migrans a. Fasciola hepatica
 Cutaneous larva migrans
 Visceral larva migrans b. Opisthorchis felineus
c. Clonorchis sinensis
D. Lung Fluke Infecti ons

a. Paragonimus westermani
b. Paragonimus kellicotti
 Drugs used for their treatment

A. Drugs used for treatment of nematodes:
1. Mebendazole
 Mechanism of action: inhibits glucose uptake and causes paralysis of
the parasite through inhibition of microtubules system
 Therabutic uses:
1. Intestinal nematodes.
2. Visceral larva migrans.
3. Hydatid disease.
4. Taenia saginatum and solium.

pharmacology
 Adverse effects: mild and infrequent because less than 10% is
absorbed.
2. Thiabendazole
 Mecanism of action: as mebendazole.
1. Treatment of strongloides and medina worm (drug of choice).
2. Cutaneous and visceral larva migrans (because it is well
absorbed).
 Adverse effects: mild GIT upset and neuropsychatric symptoms.
3. Levamisole
 Mechanism of action: causes paralysis of the parasite through
depolarizing neuromuscular blocking action. It has
immunopotentiating effect on T cell function in man.
1. Treatment of ascaris and ankylostoma.
2. As immunopotentiator in some diseases e.g. colon cancer.
 Adverse effects: mild GIT upset and skin rash.
4. Pyrantel pamoate
depolarizing neuromuscular blocking action.
1. Treatment of enterobius.
2. Treatment of ascaris, ankylostoma and mixed infection of both.
 Adverse effects: it is a safe drug.
5. Diethylcarbamazine
 Mechanism of action: it causes paralysis of microfilaria and alters
their surface structure, making them more susceptible to destruction
by host defense mechanisms.
 Therapeutic uses: treatment of filarial.
 Adverse effects: sudden death of the microfilaria can produce severs
allergic reactions e.g. fever, lymphadenopathy, leukocytosis,
esinophilia, edema , rashes.

pharmacology
B. Drugs used for treatment of trematodes
1. Praziquantel
 Mechanism of action: spastic paralysis of the parasite.
1. Treatment of schistosomiasis: active against all species.
2. Treatment of other flukes: intestinal, liver, and lung flukes.
N.B. not effective in treatment of Fasciola hepatica.
3. Cestodes: T. saginata, T.solium, D.latum, H.nana
 Adverse effects: nausea, vomiting, drowsiness, arthralgia and
myalgia.
2. Other anti-bilharzial drugs
a. Metrifonate: it is active only against Schistosoma hematobium.
b. Oxaminiquine: it is active only against Schistosoma mansoni.
3. Drugs active against Fasciola hepatica
a. Bithionol: drug of choice.
b. Dihydroemetine: alternative to bithionol.
C. Drugs used for treatment of cestodes
1. Niclosamide
 Therapeutic uses: alternative to praziquantel in treatment of T.
saginata, T.solium, D.latum, H.nana
 Adverse effects: very minimal (not absorbed from GIT).
2. Quinacrine
It is an alternative drug in the treatment of T.solium.

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Unit VI-Chemotherapy of Microbial

diseases

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I-Definitions
Antimicrobial agents:
They are any chemical substances that can kill or inhibit the growth of
microorganisms.
Antibiotics:
They are natural chemical substances obtained from living organisms which
can kill or inhibit the growth of microorganisms.
Chemotherapeutics:
They are synthetic chemical substances which can kill or inhibit the growth
of microorganisms.
Bactericidal agents:
kill infecting organism e.g. penicillin.
Bacteriostatic agents: slow growth of infecting organism (i.e. depends
greatly on active host defense mechanisms) e.g. sulphonamides.

pharmacology
A-Mechanism of action of antimicrobial agents
1-Inhibition cell wall synthesis by:
 Inhibition of peptidoglycan cross-linking (β-lactam antibiotics)

- Penicillins,
- Cephalosporins,
- Monobactams,
- Carbapenems.
 Block peptidoglycan synthesis
- Bacitracin,
- Vancomycin
2-Inhibit protein synthesis by:
 Acting at 50S ribosomal subunit

- Macrolides, chloramphenicol, lincomycin, clindamycin,
streptogramins (quinupristin, dalfopristin)
- Aminoglycosides,
- Tetracyclines
3- Inhibit folic acid pathway:
- Sulfonamides,
- Trimethoprim
4-Inhibit DNA synthesis :
- Quinolones,
- Flucytosine.
5-Inhibit mRNA synthesis:
- Rifampin
6-Disrupt cell membranes:
- Azoles,
- Polymyxins,
- Amphotericin B,
- Nystatin.
7. Unknown
- Pentamidine
B-Resistance to antimicrobial agents
pharmacology
1-Biochemical mechanisms:
 Production of inactivating enzymes

- β-lactamases → inactivate β-lactam antibiotics (penicillin,
cephalosporins, monobactam).
- Acetylase → inactivate aminoglycosides.
- Transacetylase → inactivate chlorq,phenicol
 Reduced bacterial permeability to antibiotics (tetracyclines).
 Alteration of the receptor sits on the ribosome e.g. erythromycin,
aminoglycosides.
 Development of altered metabolic pathway that bypass the reaction
inhibited by the drugs e.g. sulphonamides.
2-Genetic basis of resistance:

 Chromosomal resistance: due to spontaneous mutation of the gene
responsible for suscepetability of microorganism to antimicrobial.
 Extra-chromosomal resistance: due to transfer of genetic material
from resistant bacteria to another.
Cross resistance:
Microorganisms resistant to a certain drug may also be resistant to drugs that
share the same mechanism of action (e.g. neomycin & kanamycin) or
chemical structure (e.g. β-lactam antibiotics).
Prevention of antimicrobial resistance:
1. Prevent the misuse of antimicrobial agents: see later.
3. Use drug combination in resistant strains e.g. in T.B.
C-Selection of an antimicrobial agent
Selection from among several drugs depends upon:

1-Antimicrobial spectrums:
The susceptibility of the organism to a specific agent.
2-Host factors

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 Host factors include the following:
 Prior hypersensitivity and other adverse drug effects.
 Concomitant disease states e.g. bactericidal drugs are preferred in
immunocompromised patients.
 Impaired elimination or detoxification of the drug (this may be
genetically predetermined but more frequently is associated with
impaired renal or hepatic function due to underlying disease)
 Age of the patient
 Pregnancy status.
3-Pharmacologic factors:
 The kinetics of absorption, distribution, metabolism, and elimination
(pharmacokinetic).
 The ability of the drug to be delivered to the site of infection (which
depends on the pharmacokinetics and the available dosage forms of
the drug).
 The potential toxicity of an agent.
 Pharmacokinetic or pharmacodynamic interactions with other drugs.
4-Other factors:
The cost of antimicrobial therapy, especially when multiple agents with
comparable efficacy and toxicity are available for a specific infection.
D-Reasons for antimicrobial combination therapy

Most infections should be treated with a single antimicrobial agent.
Although indications for combination therapy exist in several cases:
 To provide broad-spectrum empirical therapy in emergent serious
infections such as septicemia (no time for bacteriological diagnosis).
 To treat mixed (polymicrobial) infections such as intra-abdominal
abscesses.
 To prevent or delay the development of resistant strains e.g.
antimicrobial combination for tuberculosis.
 To decrease dose-related toxicity by using reduced doses of one or
more components of the drug regimen e.g. flucytosine in combination
with amphotericin B for the treatment of cryptococcal meningitis

pharmacology
allows for a reduction in amphotericin B dosage with decreased
amphotericin B-induced nephrotoxicity.
 To obtain enhanced inhibition or killing (Synergism) e.g.
sulfamethoxazole + trimethoprim to form co-trimoxazole.
E-Misuses of antimicrobials
Antimicrobials are often misused in clinical practice.
The unnecessary use of antimicrobials may lead to:
 Increase toxicity.
 Superinfections (opportunistic infection): due to inhibition of bacterial
flora by the prolonged oral administration of broad spectrum
antibiotics  multiplying (superinfection) of the bacteria and fungi
that are normally inhibited by bacterial flora  diarrhea or
pseudomembranous colitis.
 Reduced efficacy of the antimicrobial agents: due to antagonism of
one drug by another or development of microbial resistance.
 Increase costs.
To avoid that; the antimicrobials should be used only when necessary and
with the following cautions:
 Proper selection
 Proper dose.
 Sufficient duration of therapy (at least for 3 days after clinical cure).
 Restrict use of valuable drug in treatment of minor infections e.g. the
use of rifampine in treatment of tonsillitis.
 Restrict use of antimicrobial combinations unless indicated.

pharmacology
II-Agents used for treatment of bacterial infections

A-Sulphonamides:
1-Chemistry:
Synthetic analogues of P-aminobenzoic acid (PABA).
They inhibit bacterial folic acid pathway ;bacteriostatic.
3-Classification:
 Oral absorbable: well absorbed from GIT, cross BBB.
- Short acting: e.g. sulfadiazine
- Long acting: e.g. sulfadoxine
 Oral poorly absorbable: e.g. sulfathalidine
 Topical:
- Sulfathiazole for wounds in absence of pus.
- Sulfamafenide for wounds and burn in presence of pus.
- Sulfacetamid eye drops for eye infections.
4-Spectrum:
 Gram +ve and Gram-ve (but narrow spectrum).
 Chlamydia, toxoplasma, and plasmodium falciparum.
5-Therapeutic uses:
 To treat infections caused by susceptible organisms, like:
 Meningococcal meningitis (sulfadiazine).
 Prophylaxis against streptococcal infection (e.g. tonsillitis) in patients
with rheumatic fever who are hypersensitive to penicillin
(sulfadiazine).
 Bacillary dysentery (sulfathalidine).
 Acute uncomplicated urinary tract infection.
 Chlamydia infection e.g. trachoma (sulfacetamide eye drops).
 Preventing infection of wounds and burn (sulfamafenide)

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6-Adverse effects:
 Hypersensitivity reactions,
 Crystalluria,
 Anemia,
 Hemolysis if G6PD deficient,
 Nephrotoxicity,
 kernicterus in infants.
7-Sulfonamide combinations:
 Co-trimoxasole (sulfamethoxazole + trimethoprim)
 Mechanism of action: inhibit two successive steps in the
enzymatic pathway of folinic acid synthesis; bactericidal.
PABA  Folic acid  Folinic acid
- -
Sulphonamides Trimethoprim
1. Respiratory tract infection due to H. influenza.
2. Complicated urinary tract infection.
3. Typhoid fever and Shigellosis.
4. Gonococcal urethritis.
Adverse effects: like sulfonamides plus: hypersensitivity
reactions, megaloplastic anemia, and teratogenicity.
 Precautions: contraindicated pregnancy due to teratogenicity.
 Other sulfonamides combinations:
a. Sulfadoxine + Pyrimethamine (Fansidar): for treatment of
malaria caused by chloroquine-resistant Plasmodium
falciparum.
b. Sulfadiazine + Pyrimethamine: for treatment of
toxoplasmosis.
c. Silver sulfadiazine: applied locally to prevent infections of
wounds and burn.

pharmacology
B-Quinolones:
1-Chemistry:
Synthetic analogues of nalidixic acid.
Inhibit DNA synthesis; bactericidal.

3-Classification and spectrum:
 1st generation: narrow spectrum (G -ve)
- e.g. nalidixic acid
 2nd generation: broad spectrum (G -ve and some G +ve)

- e.g. pipemidic acid
 3rd generation (fluoroquinolones): broader spectrum (G -ve, G +ve,
and pseudomonas)
- e.g. ciprofloxacin, norfloxacin, ofloxacin
 4th generation: extended spectrum (G -ve, G +ve, pseudomonas, and
anaerobs).
- e.g. trovafloxacin
4-Therapeutic uses:
To treat infections caused by susceptible organisms. For example:
 Urinary tract infections and prostatitis.
 Meningitis.
 Respiratory tract infections.
 Typhoid fever.
 Skin infections and osteomyelitis.
 Severe systemic infections: 3rd and 4th generations.

pharmacology
5-Adverse effects:
 GI upset (nausea, vomiting, abdominal pain),
 Skin rashes,
 Neurological side effects (headache, dizziness, visual disturbance),
 Tendonitis and tendon rupture in adults.
Precautions: contraindicated in pregnancy and in children because animal
studies show damage to cartilage.
C-Penicillins
1-Chemistry:
6-aminopenicillanic acid (contain β-lactam ring).
Inhibit bacterial cell wall synthesis; bactericidal.
3-Classification:
 Benzyl penicillin and related drugs:
- Injectional preparations:
- Benzyl penicillin (penicillin G): short acting (given every 6
hours).
- Procaine penicillin: long acting (given every 12 hours).
- Fortified procaine penicillin: longer acting (given every 24
hours).
- Benzathine penicillin: longest acting (given every 3-4
weeks).
- Oral preparations:
- phenoxymethyl penicillin (penicillin V) and phenethicillin.
 Broad spectrum penicillins:
1. Ampicillin
2. Pro-drugs of ampicillin: pivampicillin and talampicillin.
- activated only after absorption and they have better absorption
and distribution than ampicillin.

pharmacology
3. Amoxycillin: better absorption and distribution than ampicillin.
N.B. Clavulanic acid and sulbactam are β-lactamase inhibitors
combined with amoxicillin and ampicillin to include β-lactamase
producing organisms.
 Antipseudomonal penicillins: mainly used for treatment of
Pseudomonas aeruginosa infection and other G –ve rods.
1. Carbenicillin group: e.g. carbenicillin, ticarcillin.
2. Ureidopenicillin group: e.g. azlocillin, pipracillin.
 Amidinopenicillins:
1. Mecillinam: highly active against G –ve bacteria.
2. Pivmecillinam: it is prodrug of mecillinam.
 Penicillinase resistant penicillins (Antistaph penicillins): mainly
used for treatment of Staphylococcus aureus infection.
1. Methicillin
2. Cloxacillin and flucloxacillin
3. Nafcillin
4-Spectrum:
- G +ve and most G –ve bacteria
(Benzyl penicillin and related drugs not effective against G –ve
bacilli)
- Spirochetes: Tyrponoma pallidum.
- Actinomyces.
All penicillins are β-lactamase susceptible, except penicillinse
resistant penicillins (antistaph penicillins).

pharmacology
5-Therapeutic uses:
Infections caused by susceptible organisms. For example:
 Treatment of:
- Streptococcal infections e.g. throat infections.
- Staphylococcal infections e.g. pyrogenia infections.
- Pneumococcal infections e.g. pneumonia.
- Meningococcal meningitis.
- Syphilis and gonorrhoea.
- Typhoid and paratyphoid fevers: ampicillin and amoxicillin.
- Pseudomonas infection: antipseudomonal penicillins.
- Actinomycosis and anthrax.
- Diphetheria, tetanus, and gas gangrene (together with
antitoxins).
 Prophylaxis:
- Prevent recurrence of acute rheumatic fever: benzathine
penicillin.
- Prevent gonorrheal ophthalmia in neonates: benzyl penicillin
eye drops.
- Prevent subacute bacterial endocarditis before dental extraction.
6-Adverse effects:
 Hypersensitivity reactions (10% of patients),
 GIT upset (anorexia, nausea, vomiting, diarrhea)
D-Cephalosporins:
1-Chemistry:
7-aminocephalosporanic acid (contain β-lactam ring).
2-Mechanism of action: as penicillins.
3-Classification and Spectrum:
 1st generation:
- e.g. cephadroxil, cephradine, cephalexin
- spectrum: more on G +ve.
 2nd generation:
- e.g. cefaclor, cefuroxime, cefoxitin
pharmacology
- spectrum: G –ve and G +ve.
 3rd generation:
- e.g. cefixime, cefotaxime, cefoperazone, ceftriaxone
- spectrum: more on G –ve and pseudomonas.
 4th generation:
- e.g. cefepime
- spectrum: G –ve, G +ve, pseudomonas, and anaerobes.
4-Therapeutic uses:
 Bacterial meningitis.
 Skin, bone, joint infections.
 Urinary tract infection.
 Pelvis, abdomen, and chest infections caused by mixed organisms.
 Bacteraemia of unknown organism.
 Pseudomonal infection.
 Penicillin resistant streptococcal infection.
 Penicillin resistant gonococci.
5-Adverse effects:
 Hypersensitivity reactions
 Nephrotoxicity.
E-Aminoglycosides:
 Streptomycin
 Gentamicin
 Neomycin
 Kanamycin
 Amikacin
 Tobramycin
1-Chemistry:
Amine-containing carbohydrate.
They are either natural products or derivatives of soil actinomycetes.

pharmacology
They inhibit protein synthesis by binding to the 30 S bacterial ribosomal
subunit; bactericidal.
3-Spectrum:
Mainly on G –ve and few G +ve (narrow spectrum).
4-Therapeutic uses:
 Streptomycin and kanamycin:
- Orally for sterilization of intestine before surgery and bacillary
dysentery.
- Treatment of TB
 Neomycin:
dysentery.
- Orally in hepatic coma to kill flora of the gut (to decrease
production of ammonia)
 Gentamicin, tobramycin, amikacin:
- Treatment of pneumonia, urinary tract infections, and
osteomylitis.
- Treatment of peritonitis (with penicillin and metronidazole).
- Pseudomonas infections (with carbenicillin).
- Topically for skin and eye infections.
5-Adverse effects:
 Ototoxicity (especially when used with loop diuretics),
 Nephrotoxicity (especially when used with cephalosporins),
 Neuromuscular block.

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F-Tetracycline:
 Tetracycline
 Doxycycline
 Demeclocycline
 Minocycline
1-Chemistry:
They have different chemical structures and are produced by different
species of Streptomyces.
subunit; bacteriostatic.
3-Spectrum:
 Most G +ve, G –ve, and some anaerobes.
 Rickettsia, coxiella, mycoplasma and Chlamydia, and brucella.
 Spirochetes, actinomyces, protozoa.
4-Therapeutic uses:
 Treatment and prophylaxis of Cholera.
 Mixed bacterial infection of respiratory tract e.g. sinusitis, bronchitis.
 Second choice after penicillins in Syphilis, Gonorrhea, Actinomycosis,
Anthrax, and Shigellosis.
 Diseases caused by Rickettsia (typhus) and Coxiella.
 Chlamydial disease e.g trachoma.
 Treatment of Brucellosis and Plague.
 Treatment of Mycoplasma pneumoniae.
 Treatment of acne vulgaris (doxycycline and minocycline).
 Bacillary and Ameoebic dysentery.
 Treatment of chloroquin resistant P. falciparum (with quinidine).
 Local for eye and skin infections.

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5-Adverse effects:
 GIT distress
 Discolor of teeth
 Inhibition of bone growth in children,
 Photosensitivity,
 Hepatotoxicity,
 Nephrotoxicity,
 Teratogenicity.
Precautions:
Contraindicated in pregnancy, lactation, children (less than 8 years of age).

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G-Macrolides:
 Erythromycin
 Azithromycin
 Clarithromycin
1-Chemistry:
They consist of a large lactone ring to which sugars are attached.
subunit; bacteriostatic in low concentration and bactericidal in high
concentration.
3-Spectrum:
 Mainly G +ve bacteria
 Mycoplasma and Chlamydia.
4-Therapeutic uses:
 Treatment of Staphylococcal, Streptococcal, Pneumococcal,
H.influenza, Gonorrhea and Syphilis infections in penicillin-sensitive
patients.
 Eradication of Corynbactrium diphtheriae from pharyngeal carriers.
 Treatment of Mycoplasma pneumonia infections in infants.
 Treatment of Chlamydial infections in pregnancy and infants.
 Treatment of Toxoplasma infection (clarithromycin).
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5-Adverse effects:
 GIT discomfort (most common cause of noncompliance)
 Acute cholestatic hepatitis
 Eosinophilia
 Skin rashes.
H-Antiseptics and disinfectants
Disinfection refers to the inactivation or killing of pathogens (protozoa,
bacteria, fungi, viruses) in the human environment.
Sterilization refers to the killing of all microorganisms, whether pathogenic,
dormant, or nonpathogenic.
Antisepsis refers to the reduction by chemical agents of numbers of
microorganisms on skin and mucosal surface.
Properties of an ideal disinfectant:
 Broad spectrum of activity.

 High potency under conditions of use.
 Ready solubility or miscibility with water.
 Non caustic with a low degree of toxicity and without harmful or
sensitizing effects on delicate tissues.
 Complete compatibility with other antimicrobial agents.
 Stable on storage and over a wide pH range.
 Economical, no offensive odor, non-staining.
1-Phenols:
 Crude phenols or its derivatives (dettols, lysols, cresols).

Not inactivated by organic matter but they are toxic and irritant.
2-Alcohols:
- 70 % ethanol & 50 - 70 % isopropyl alcohol.
They should not be diluted to be effective.

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3-Oxidizing agents:
 Hydrogen peroxide for infected wounds.
 Potassium permanganate for superficial fungal infection.
 Halogens: e.g.:
o Chlorine: disinfection of water.
o Hypochlorite compounds for fomites and clothes .
o Iodine tincture is the best skin disinfectant.
4-Cationic surface active agents: (detergents and soaps).
 Cetavlon,
 Zephiran
 Cetrimide.
Non toxic, non irritant compounds.
Bound to and inactivated by plant fibers (cotton & gauze).
5-Salts of heavy metals:
 Mercurochrome for wound infections.

 Merthiolate for preservation of vaccines.

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I-Agents used for the treatment of Tuberculosis (TB)
 Tuberculosis (TB) is caused by TB bacilli (Mycobacterium
tuberculosis).
 Anti-tuberculus drugs must be highly lipid soluble to penetrate cell
membrane of the host and lipid coat of the TB bacilli (streptomycin is
exception).
I- 1st line drugs: II- 2nd line drugs:

1. Isoniazide (INH). 1. Capreomycin.
2. Rifampin. 2. Cycloserine.
3. Ethambutol. 3. Fluorinated quinolones.
4. Streptomycin. 4. Para amino salicylic acid (PAS).
5. Pyrazinamide. 5. Kanamycin.
I- 1st line drugs:
 Isonizid (INH)
 Mechanism of action: decreases synthesis of mycolic acids→↓ cell
wall synthesis.
1. Treatment of active TB.
2. Prophylaxis against TB in certain cases e.g. close contact to recent
diagnosed cases.
 Adverse effects: hemolysis if G6PD deficient, neurotoxicity
(peripheral neuropathy, optic neuritis), hepatotoxicity, SLE-like
syndrome.

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 Rifampin
 Mechanism of action: Inhibits DNA-dependent RNA polymerase→↓
RNA synthesis.
2. Treatment of leprosy.
3. Treatment of resistant staphylococcal infections and prostatitis.
4. Treatment of meningococcal carrier state.
5. Prophylaxis in contacts of children with H. influenzae type B.
6. Treatment of Pox virus (it interferes with envelope formation).
 Adverse effects: mild hepatotoxicity, drug interactions (↑ P450), and
red/orange body fluids (harmless).
 Ethambutol
 Mechanism of action: unknown (ma be due to ↓ RNA synthesis).
 Therapeutic uses: treatment of active TB.
 Adverse effects: visual disturbances (field defects, color blindness,
optic neuritis), peripheral neuritis, hyperuricemia.
 Pyrazinamide
 Used in combination with INH and rifampin to minimize resistance.
 Adverse effects: hepatotoxicity, hyperuricemia.
 Streptomycin
 Used in combination with INH and rifampin to treat military TB,
extensive pulmonary and renal TB.
 Adverse effects: see aminoglycosides.
II- 2nd line drugs:
 They are less effective and more toxic than 1st line drugs.
 For example; para amino salicylic acid (PAS) causes bone marrow
depression, gastric ulceration, thyroid injury, and neurological
symptoms.
 They used only when resistance or severe side effects developed to 1 st
line drugs.

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 Regimen of TB therapy:
1. Initial intensive course (2-4 months):
- At least 3 drugs are used (INH + Rifampin + Pyrazinamide).
- A 4th drug may be added if resistance is possible (Etambutol or
Streptomycin).
2. Continuation phase (4-12 months):
- (INH + Rifampin) and Ethambutol may be added if resistance is
suspected.

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J-Agents used for the treatment of Leprosy
Leprosy is the disease caused by Mycobacterium leprae.
1-Dapson
Chemistry:
Structural analogue of PABA and chemically related to sulfonamides.

Mechanism of action: similar to sulfonamides.
Therapeutic uses:
Treatment of leprosy (given for 2-4 years with rifampin and/or clofazimne to
avoid development of resistance)
Adverse effects: similar to sulfonamides.
2-Clofazimine
Chemistry: phenazine dye.
Mechanism of action: inhibit mycobactria DNA synthesis; bactericidal.
Therapeutic uses:
Treatment of leprosy (with rifampin and clofazimne to avoid development of
resistance)
Adverse effects: abdominal pain, atropine like effects, dark brown
discoloration of skin, cornea, and all body fluids.
3-Rifampin:
It is the most active antilepromatous drug available.

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III-Antifungal agents
Fungal infections (mycosis) are usually confined to the skin or mucous
membranes (local or superficial mycosis).
However, in immune deficiency states, internal organs may also be affected
(systemic or deep mycosis).
Agents used for superficial fungal infections
 Azoles.
 Polyenes antibiotics:
- Nystatin,
- Amphotricin-B.
 Grisofulvin
 Non related topical antifungal:
- Naftifine
- Ciclopiroxolamine
- Haloprogen.
 Old topical agents: Whitfield ointment, gentian violet, tincture iodine.
Agents used for systemic fungal infections
 Azoles.
 Amphotricin-B.
 Flucytosin
A-Azoles:
 Fluconazole,
 Ketoconazole,
 Clotrimazole,
 Miconazole,
 Itraconazole
They disrupt cell membrane permeability (by inhibiting ergosterol
synthesis).

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2-Therapeutic uses:
 Superficial fungal infection:
- Dermatophytes infection of skin (e.g. tinea), hair (e.g.
ringworm), and nail (e.g. paronychia).
- Mucocautaneous candidiasis: e.g. oropharyngeal and
vulvovaginal candidiasis.
 Systemic fungal infections: e.g. cryptococcal meningitis in AIDS
patients (fluconazole).
3-Adverse effects:
 Hepatotoxicity
 Microsomal enzyme inhibition,
 Antianderogenic effects (impotence and gynecomastia)
 Fluid retention.
B-Polyenes antibiotics:
 Nystatin
 Amphotricin-B
They disrupt cell membrane (by forming membrane pores that disrupt
homeostasis).
2-Therapeutic uses:
 Local uses (amphotricin-B and nystatin topically):
- Eye drops for fungal corneal ulcers.
- Lozenges for oral candidiasis.
- Tablets for intestinal candidiasis.
- Vaginal tablets for vaginal candidiasis.
 Systemic (amphotricin-B only by parenteral route):
- Systemic mycosis (i.v.).
- Intrathecally for fungal meningitis (can not cross blood brain
barrier).
- American leshmaniasis (i.v.).

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3-Adverse effects (iv. injection of amphotricin-B):
 Hepatotoxicity,
 Nephrotoxicity,
 Direct myocardial toxicity (arrhythmia, hypotension),
 Fever, chills, and headache.
C-Grisofulvin
It interferes with microtubule function, disrupts mitosis. Deposits in keratin-
containing tissues (e.g., nails).
2-Therapeutic uses:
It is given orally for:
 Superficial fungal infection: dermatophytes infection of skin (e.g.
tinea), hair (e.g. ringworm), and nail (e.g. paronychia).
N.B. it deposits in keratin-containing tissues (e.g. skin and nails).
3-Adverse effects:
 Hepatotoxicity
 Leukopenia
 Photosensitivity
 Nausea, vomiting
 Teratogenicity and carcinogenicity.
D-Flucytosin
It inhibits DNA synthesis.
2-Therapeutic uses:
 Systemic mycosis
 Fungal meningitis.

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3-Adverse effects:
 Hepatotoxicity,
 Bone marrow depression,
 Loss of hair
E-Non related topical antifungal:

 Naftifine: effective only against skin dermatophytes.
 Ciclopirox olamine: broad spectrum against dermatophytes and

yeasts.
F-Old topical agents:
 Whitfield ointment (salicylic acid + benzoic acid + vaseline): act as
keratolytic and fungicidal (to remove infected keratin).

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IV-Antiviral agents

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Steps of viral replication and main sites of action of antiviral drugs:

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A-Anti-herpes virus agents:
1-Acyclovir:
It preferentially inhibits viral DNA polymerase when phosphorylated by
viral thymidine kinase.
Therapeutic uses:
 treatment of Herpes simplex virus (HSV),
 varicella zoster virus (VZV).
 Prophylactic in immunocompromised patients.
Adverse effects:
 Neurotoxicity (delirium, tremor),
 Nephrotoxicity.
2-Ganciclovir
Mechanism of action: similar to acyclovir.
Therapeutic uses:
As acyclovir, but mostly used in treatment and prophylaxis of CMV
(especially in immunocompromised patients).
Adverse effects:
 Leukopenia
 Neutropenia
 Thrombocytopenia
 Nephrotoxicity
 More toxic to host enzymes than acyclovir.

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3-Foscarnet:
Viral DNA polymerase inhibitor that binds to the pyrophosphate binding site
of the enzyme (pyrofosphate analog). Does not require activation by viral
kinase.
Therapeutic uses:
As ganciclovir, with increased activity versus acyclovir-resistant strains of
HSV.
Adverse effects: nephrotoxicity.

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B-Anti-retroviral agents
1-Protease inhibitors:
 Saquinavir
 Ritonavir
 Indinavir
 Nelfinavir
They inhibit assembly of new virus by blocking protease enzyme.
Adverse effects:
 GI intolerance (nausea, diarrhea),
 Hyperglycemia
 Lipid abnormalities
 Thrombocytopenia (indinavir).
2-Reverse transcriptase inhibitors
 Nucleosides:
- Zidovudine (AZT),
- Didanosine (ddI), Zalcitabine (ddC),
- Stavudine (d4T),
- Lamivudine (3TC)
 Non-nucleosides:
- Nevirapine,
- Delavirdine
They preferentially inhibit reverse transcriptase of HIV; prevent
incorporation of viral genome into host DNA.
Adverse effects:
 Bone marrow suppression (neutropenia, anemia),
 Peripheral neuropathy,
 Lactic acidosis (nucleosides);
 Rash (non-nucleosides);
 Megaloblastic anemia (AZT).

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Therapeutic use of anti retroviral agents:
They are used in HIV infection (Human immunodeficiency virus) (AIDS).
 HIV Triple therapy: entails use of two nucleoside reverse
transcriptase inhibitors with a protease inhibitor, though other
combinations, such as the substitution of a non-nucleoside for a
protease inhibitor, are used. Initiated when patients have low CD4
counts (< 500 cells/mm3) or high viral load.
 AZT used during pregnancy to reduce risk of fetal transmission.

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C-Other antiviral agents

1-Gamma globulin (immune globulin)
 They are antibodies concentrated from plasma of persons with high
antibody levels or prepared by genetic engineering.
 Mechanism of action: attach to the envelope of susceptible virus and
block its penetration into the host cell (passive immunization).
 Therapeutic uses: non specific (all viral infections) but must be given
early by IV or IM injections.
 Adverse effects: hypersensitivity reactions.
2-Amantadine
 Mechanism of action: blocks viral penetration/uncoating. Also causes
the release of dopamine from intact nerve terminals.
 Therapeutic uses: prophylaxis for influenza A, Parkinson’s disease.
 Adverse effects: ataxia, dizziness, slurred speech.
3-Ribavirin
 Mechanism of action: inhibits synthesis of guanine nucleotides by
competitively inhibiting IMP dehydrogenase.
 Therapeutic uses: pneumonia and bronchiolitis of infancy caused by
respiratory syncytial virus (RSV).
 Adverse effects: hemolytic anemia, upper airway irritation
4-Interferons
 They are natural endogenous glycoproteins.
 Mechanism of action: interferon-α (from human leukocytes) blocks
various stages of viral RNA and DNA synthesis.
 Therapeutic uses: Chronic hepatitis C and B, Kaposi’s sarcoma.
 Adverse effects: neutropenia, flu-like symptoms (fatigue, depression,
muscle weakness), hepatic dysfunction.

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5-Rifampin
 It inhibits assembly of poxvirus by preventing the envelope formation.
It is not used in treatment of human poxvirus infection but topical
application can inhibit human vaccinia lsions.
V-Idea about vaccines and Toxoids

Vaccines:
They are weapons to prevent diseases. They may be made of
microorganisms similar to the ones that cause diseases, or of the toxins
produced by the microorganisms after changing them into harmless toxoids.
Types of vaccines:
 Live vaccines: containing live attenuated microorganisms.
 Killed vaccines: containing killed microorganisms.
 Recombinant vaccines: produced by genetic engineering.
 Toxoids: toxins produced by the bacteria after making them harmless.
N.B. Dangerous to give live vaccines to immunocompromised patients or
their close contacts.
A-Viral vaccines
 Live attenuated vaccines: e.g. measles, mumps, rubella, and Sabin
polio vaccine against poliomyelitis.
 Killed vaccines: e.g. Salk polio vaccine against poliomyelitis.
 Recombinant vaccines: hepatitis B vaccine (antigen = recombinant
HBsAg).
MMR = measles, mumps, and rubella vaccines.
OPV = oral polio vaccine = Sabin vaccine.
IPV = injection polio vaccine = Salk vaccine.

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B-Bacterial vaccines and toxoids
 Live attenuated vaccines: e.g. BCG vaccine against TB (tuberculosis).

 Killed vaccines: e.g. pertussis (whooping cough) vaccine
 Toxoids: e.g. diphtheria toxoid, tetanus toxoid
DPT = diphtheria toxoid, pertussis vaccine, and tetanus toxoid.
DT = diphtheria and tetanus toxoids.
TT = tetanus toxoid

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What damages vaccines?
1. All vaccines lose their potency after a certain time, even with good care.
You know that time from the expiry date printed on the vaccine.
2. Heat and sunlight can damage vaccines, especially the live attenuated
ones.
3. Freezing damages vaccines, except the live attenuated ones.
4. Disinfectants or antiseptics can damage vaccines (such as spirits and
detergents) and antibiotics (such as streptomycin on BCG).

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Unit VII-Antineoplastics and

Immunosuppressants

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I-Cancer chemotherapy
A-Definitions:
 Tumor (neoplasm) consists of cells that proliferate independently of
the body’s inherent “building plan.”
 Malignant tumor (cancer) is present when the tumor tissue

destructively invades healthy surrounding tissue or when dislodged
tumor cells form secondary tumors (metastases) in other organs.
 Cancer chemotherapy consists of drugs which used in the treatment

of cancers. A cure requires the elimination of all malignant cells
(curative therapy). When this is not possible, attempts can be made
to slow tumor growth and thereby prolong the patient’s life or
improve quality of life (palliative therapy).
 Log-kill hypothesis: cytotoxic drugs act by first-order kinetics; that

is, at a given dose, they kill a constant fraction of the tumor cells
rather than a fixed number of cells.
B-Combination therapy:
The combined use of two or more drugs often is superior to single-agent
treatment in many cancers, and certain principles have been used in
designing such treatments:
 Each drug used in the combination regimen should have some
individual therapeutic activity against the particular tumor being
treated.
 Drugs that act by different mechanisms may have additive or
synergistic therapeutic effects. Tumors may contain heterogeneous
clones of cells that differ in their susceptibility to drugs. Combination
therapy will thus increase log cell kill and diminish the probability of
emergence of resistant clones of tumor cells.

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 Drugs with different dose-limiting toxicities should be used to avoid
cumulative damage to a single organ.
 Intensive intermittent schedules of drug treatment should allow time
for recovery from the acute toxic effects of antineoplastic agents,
primarily bone marrow toxicity. The use of non myelosuppressive
agents can be considered during the recovery period.
 Several cycles of treatment should be given, since one or two cycles
of therapy are rarely sufficient to eradicate a tumor. Most curable
tumors require at least six to eight cycles of therapy.
The chemotherapy of advanced Hodgkin’s disease is one of the best

examples of successful combination chemotherapy. Combination therapy
with the MOPP regimen (Mechlorethamine, Oncovin [vincristine],
Procarbazine, Prednisone), alternating with ABVD (Adriamycin
[doxorubicin], Bleomycin, Vinblastine, Dacarbazine), has resulted in cure
rates of 50 to 60%.
C-Cell cycle and anticancer therapy
Cell cycle consists of phases that all cells -normal and neoplastic- must
traverse before and during cell division.
 G1 (growth)
 S (synthesis of DNA)
 G2 (growth)
 M (mitosis: prophase–metaphase– anaphase–telophase).
 G0 (quiescent G1 phase)
G1 and G0 are of variable duration. Mitosis is usually shortest phase. Most

cells are in G0.
Rapidly dividing cells have a shorter G1.
Many of the effective anticancer drugs exert their action on cells traversing
the cell cycle (proliferating cells) and are called cell cycle-specific (CCS)
drugs. In most cases, they are also phase- specific; for example,

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hydroxyurea and cytarabine kill only cells in the S-phase. Similarly,
bleomycin is most toxic to cells in G2- and early M-phases.
A second group of agents called cell cycle-nonspecific (CCNS) drugs can
sterilize tumor cells whether they are cycling or resting in the G0
compartment. CCNS drugs can kill both G0 and cycling cells (although
cycling cells are more sensitive).
In general, CCS drugs are most effective in hematologic malignancies and in
solid tumors in which a relatively large proportion of the cells are
proliferating or are in the growth fraction. CCNS drugs are particularly
useful in low growth fraction solid tumors as well as in high growth fraction
tumors.

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II-Classification of drugs
A-Alkylating agents:
They are the largest class of anticancer agents. They are compounds that are
capable of introducing alkyl groups into nucleophilic sites on other
molecules within cells through the formation of covalent bonds.The
macromolecular sites of alkylation damage include DNA, RNA, and various
enzymes.
 Nitrogen mustards:
- Cyclophosphamide
- Chlorambucil
- Melphalan
- Ifosfamide
- Mechlorethamine hydrochloride.
 Alkyl sulfonates:
- Busulfan
 Nitrosoureas:
- Carmustine
- Lomustine
- Semustine
- Streptozocin.
 Ethylenimines :
- Thiotepa
 Triazenes:
- Dacarbazine
B-Antimetabolites:
 Folate antagonist:
- Methotrexate
 Purine analogues:
- mercaptopurine (6-MP),
- thioguanine,
- fludarabine,

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- pentostatin,
- cladribine.
 Pyrimidine analogues:
- fluorouracil (5-FU, 5-fluorouracil),
- cytarabine (cytosine arabinoside)
They are drugs structurally related to naturally occurring compounds, such

as vitamins, amino acids, and nucleotides.
These drugs can compete for binding sites on enzymes or can themselves
become incorporated into DNA or RNA and thus interfere with cell growth
and proliferation.
C-Antibiotics
 Anthracyclines:
- Doxorubicin,
- Daunorubicin,
- Idarubicin.
 Bleomycins: (bleomycin sulfate )
 Mitomycin (mitomycin C)
 Dactinomycin (actinomycin D)
 Plicamycin
D-Plant-derived products
 Vinca alkaloids:
- Vincristine
- Vinblastine
 Epipodophyllotoxins:
- Etoposide
- Teniposide
 Taxanes:
- Paclitaxel

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E-Enzymes:
 L-Asparaginase
F-Hormonal agents
 Glucocorticoids.
 Androgens /antiandrogens
- flutamide
 Estrogens/ antiestrogens
- tamoxifen citrate,
- estramustine phosphate sodium.
 Progestins
 Luteinizing hormone–releasing hormone (LH-RH) antagonists:
- buserelin,
- leuprolide
 Octreotide acetate
G-Miscellaneous agents
 Cisplatin (cis-platinum II)
 Procarbazine (N-methylhydrazine)
 Mitotane
 Hexamethylmelamine (HMM)
 Hydroxyurea
 Carboplatin
 Mitoxantrone
H-Monoclonal antibodies
 Bevacizumab
 Trastuzumab
 Rituximab
 Gemtuzumab

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I-Immunomodulating agents
 Levamisole
 Interferons : (interferon alfa-2a, interferon alfa-2b)
 Interleukins: aldesleukin (interleukin-2, IL-2, Proleukin)
J-Cellular growth factors:
 Filgrastim,
 Sargramostim
III-Agents used in cancer
Ideal anticancer drugs would eradicate cancer cells without harming normal
tissues. Unfortunately, no currently available agents meet this criterion, and
clinical use of these drugs involves a weighing of benefits against toxicity in
a search for a favourable therapeutic index.
1-Methotrexate:
Mechanism:
S-phase-specific antimetabolite. Folic acid analog that inhibits dihydrofolate
reductase, resulting in decreased DNA and protein synthesis.
Clinical use:
 Leukemias,
 Lymphomas,
 Choriocarcinoma,
 Breast carcinoma,
 Sarcomas.
 Rheumatoid arthritis,
 Psoriasis.
Toxicity:
 Bone marrow suppression -which is reversible with leucovorin
(folinic acid)
 Crystalluria.

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2- 5-fluorouracil (5-FU):
Mechanism:
S-phase-specific antimetabolite. Pyrimidine analog, bioactivated to inhibits
thymidylate synthase, resulting in decreased DNA and protein synthesis.
Clinical use:
 Colon cancer and other solid tumors,
 Basal cell carcinoma (topical).
Synergy with methotrexate.
Toxicity:
 Bone marrow suppression -which is NOT reversible with leucovorin-,
 GI irritation,
 Alopecia.
3-6-Mercaptopurine (6MP)
Mechanism:
Blocking purine synthesis.
Clinical use:
 Leukemias,
 Lymphomas (not Chronic lymphoid or Hodgkin’s lymphomas)
Toxicity:
 Bone marrow suppression,
 GI irritation
 Hepatotoxicity.
Metabolized by xanthine

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4-Busulfan
Mechanism:
Alkylating agent.
Clinical use:
CML (chronic myeloid lymphoma).
Toxicity:
 Pulmonary fibrosis
 Hyperpigmentation.
5-Cyclophosphamide
Mechanism:
Alkylating agent.
It requires bioactivation by liver.
Clinical use:
 Non-Hodgkin’s lymphoma,
 Breast and ovarian carcinomas.
 Also an immunosuppressant.
Toxicity:
 Hemorrhagic cystitis
 Hepatotoxicity.
6-Nitrosureas
Mechanism:
Alkylating agent.
It requires bioactivation.
It crosses blood–brain barrier →CNS.

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Clinical use:
Brain tumors.
Toxicity:
CNS toxicity (dizziness, ataxia).
7-Cisplatin:
Mechanism:
It acts like an alkylating agent.
Clinical use:
 Testicular, bladder, ovary, and lung carcinomas.
Toxicity:
 Nephrotoxicity
 Acoustic nerve damage.
8-Doxorubicin (adriamycin)
Mechanism:
It intercalates in DNA creating breaks to decrease replication and
transcription and generate free radicals.
Clinical use:
 Hodgkin’s lymphoma (ABVD regimen),
 Myelomas
 Sarcomas
 Solid tumors (breast, ovary, lung).
Toxicity:
 Bone marrow suppression
 Cardiotoxicity (delayed congestive heart failure)
 Marked alopecia.

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9-Bleomycin
Mechanism:
G2-phase-specific intercalates DNA strands, induces free radical formation,
causing strand breaks.
Clinical use:
 Testicular cancer
 Lymphomas.
Toxicity:
 Pulmonary fibrosis,
 Skin changes (blisters),
 Minimal bone marrow suppression.
10-Etoposide:
Mechanism:
G2-phase-specific inhibits topoisomerase II so that double-strand breaks
remain in DNA following replication, with subsequent DNA degradation.
Clinical use:
 Oat cell carcinoma of the lung and prostate,
 Testicular carcinoma.
Toxicity:
 GI irritation,
 Alopecia.
11-Prednisone
Mechanism:
It may trigger apoptosis. It may even work on non-dividing cells.

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Clinical use:
 Most commonly used glucocorticoid in cancer chemotherapy.
 Used in CLL (chronic lymphoid lymphoma), Hodgkin’s lymphomas
(MOPP regimen).
 Also an immunosuppressant used in autoimmune diseases.
Toxicity:
 Cushing-like symptoms
 Immunosuppression,
 Cataracts
 Acne
 Osteoporosis
 Hypertension
 Peptic ulcers
 Hyperglycemia.
12-Tamoxifen/ raloxifene
Mechanism:
Estrogen receptor mixed agonist/antagonist that blocks the binding of
estrogen to estrogen receptors.
Clinical use: Breast cancer.
Toxicity: may increase the risk of endometrial carcinoma via partial agonist
effects.
13-Vincristine (Oncovin) and vinblastine
Mechanism:
M-phase-specific alkaloid that binds to tubulin and blocks polymerization of
microtubules so that mitotic spindle can’t form.

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Clinical use:
 Vincristine (Oncovin): Hodgkin’s lymphoma (MOPP regimen),
leukemias, Wilms’ tumor.
 Vinblastine: Hodgkin’s lymphoma (ABVD regimen), testicular
carcinoma, Kaposi’s sarcoma.
Toxicity:
 Vincristine: neurotoxicity (areflexia, peripheral neuritis).
 Vinblastine: bone marrow suppression, GI irritation, alopecia.
14-Paclitaxel
Mechanism:
M-phase-specific agent obtained from yew tree that binds to tubulin and
hyperstabilizes polymerized microtubules so that mitotic spindle can’t break
down (anaphase cannot occur).
Clinical use:
Ovarian and breast carcinomas.
Toxicity:
Bone marrow suppression and hypersensitivity.

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IV-Immunopharmacology
A-Idea about immune response
The immune system mediates the individual’s relationship with the
microbial environment.
It is divided into two functional divisions:
 Non-specific (innate) (natural) immune response:
It is the first line of defense against infectious agents.
 Specific (adaptive) (acquired) immune response; which is
subdivided into:
- Humoral immune response (antibodies formation by B-
lymphocytes).
- Cell mediated immune response by T- lymphocytes.
The essential difference between the two types of immunity lies in the
means by which microorganisms are recognized.
In innate immunity, glycolipids and macromolecules with repeat patterns
that are unique to infectious organisms are recognized by cell surface
receptors on macrophages, dendritic cells, natural killer (NK) and NK T
(NKT) cells, as well as by the complement system.
In acquired immunity, lymphocytes (B cells and T cells) use very specific
antigen receptors to recognize infectious agents and other antigens, either
directly or when processed by antigen-presenting cells (APCs), such as
dendritic cells. Thus, an interplay exists between innate and acquired
immunity at the level of the APC.
Once an otherwise healthy person has had an infection with bacteria or with
a virus, the immune system recognizes that pathogen and prevents its
recurrence. In addition, the immune system has the remarkable capacity to
discriminate between antigens, even if their structures are closely related.
The immune response needs to be able to distinguish between self and non-
self antigens. Otherwise, T cells and antibodies would constantly be
attacking autologous cells, tissue components, or even commensal bacteria.
In the 1950s, Sir Frank Macfarlane Burnet first proposed that in the prenatal

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state, the interaction of self- antigens with antigen-specific lymphocytes
leads to the elimination of self-reactive lymphocytes and hence to
immunologic tolerance. When immunologic tolerance breaks down, the
antibodies and sensitized (antigen-reactive) cells that are directed against
self-antigens cause autoimmune diseases.

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B-Specific immunosuppressive agents
1-Cyclosporine
It binds to cyclophilins→ blocking the differentiation and activation of T
cells (mainly by inhibiting the production of IL-2 and its receptor).
Clinical use:
 It suppresses organ rejection after transplantation,
 Selected autoimmune disorders.
Toxicity:
 Nephrotoxicity
 Peripheral neuropathy
 Hyperglycemia
 Hyperlipdiaemia
 Hypertension,
 Gingival hyperplasia
 Hirsutism
2-Tacrolimus
Similar to cyclosporine; it binds to FK-binding protein, inhibiting secretion
of IL-2 and other cytokines.
Clinical use:
 Potent immunosuppressive used in organ transplant recipients (more
potent than cyclosporine).
Toxicity:
Similar to cyclosporine except gingival hyperplasia & hirsutism.

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3-Rapamycin (Sirolimus)
It is structurally related to tacrolimus. It blocks IL-2-dependent T-cell
proliferation.
Clinical use:
It is approved for use as an adjunctive agent in combination with
cyclosporine for prevention of acute renal allograft rejection.
Toxicity:
 Bone marrow suppression ( leucopenia, thrombocytopenia, anaemia),
 Diarrhoes,
 Rash,
 Hyperlipidaemia
4-Azathioprine:
It is a cytotoxic drug; metabolized to 6-Mercaptopurine that interferes with
the metabolism and synthesis of nucleic acid.
Toxic to proliferating lymphocytes after antigenic stimulus.

It affects all rapidly dividing cells.
Clinical use:
 Kidney transplantation
 Autoimmune disorders (including glomerulonephritis and hemolytic
anemia).
Toxicity:
 Nausea, vomiting,
 GI ulceration
 Diarrhea,
 Decreased wound healing
 Alopecia,
 Increased risk of infection,
 Increased cancer risk.

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5-Other cytotoxic drugs:
 Cyclophosphamide
 Methotrexate
6-Mycophenolate Mofetil
Mechanism:
It inhibits lymphocyte proliferation.
Clinical use:
In conjunction with cyclosporine and corticosteroids for prevention of organ
rejection in patients receiving allogeneic renal and cardiac transplants.
Toxicity:
GI side effects are most common (nausea, vomiting, diarrhoea).
7-Glucocorticoids:
 Prednisone
 Prednisolone
They inhibit cytokine gene expression;  IL-1 secretion & IL-2 synthesis &
release,  lymphocytes,  monocytes, and  macrophage function.
Clinical use:
 Used alone or in combination with other agents in the treatment of
autoimmune disorders and for the prevention of transplant rejection.
Toxicity:
 Immunosuppression
 Cataracts
 Acne
 Osteoporosis
 Hypertension
 Peptic ulcers
 Hyperglycemia.

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8-Monoclonal antibodies:
 Muromonab-(CD3)
It blocks antigen recognition by T-cell (CD3).
Clinical use:
Prevention of acute allograft rejection in kidney and hepatic transplants and
as prophylaxis in cardiac transplantation.
Toxicity:
 Fever
 Headache
 Dyspnoea
 Pulmonary edema
 Anaphylaxis.
9-Rho(D) Immune globulin
It is a preparation of human IgG that contains a high titer of antibodies
against the Rho (D) red cell antigen.
Clinical use:
Administer to Rh-negative mother within 72 hours of delivery of an Rh-
positive infant to prevent Rh hemolytic disease in future newborns (prevent
the mother from becoming sensitized to the Rh antigen by binding to and
destroying fetal red blood cells that have entered her blood).

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C-Idea about Immunostimulants

A number of disorders can be treated with immunostimulating agents (also
known as biological response modifiers or immunomodulating agents).
These conditions include immunodeficiency diseases, cancer, some types of
viral and fungal infections, and certain autoimmune disorders.
Immunostimulating agents are non specific; they cause general stimulation
of the immune response.
These drugs may work on cellular or humoral immune systems or both.
1-Bacillus Calmette-Guérin (BCG)
 It is a viable attenuated strain of Mycobacterium bovis.
 It stimulates T cells and natural killer cells, which in turn can kill
malignant cells.
 BCG immunotherapy has been most successful in the treatment of
bladder cancers.
 The most dangerous complications are severe hypersensitivity and
shock. Chills, fever, malaise, immune complex, and renal disease are
among the other side effects.
2-Levamisole:
 It was originally developed as an antihelminthic drug.
 It potentiates the stimulatory effects of antigens, mitogens,
lymphokines, and chemotactic factors on lymphocytes, granulocytes,
and macrophages. It has been shown to increase T cell–mediated
immunity.
 It has been used successfully in treating chronic infections. It also has
been approved for use in combination with fluorouracil in the
treatment of colorectal cancer.

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4-Thymic factors:
 Thymic humoral factor
 Thymosin fraction 5
 Thymodulin
 They are naturally occurring substances isolated from a calf thymus
extract that promote T-lymphocyte differentiation.
 They are used to enhance T-lymphocytic functions. Thymic factors
have been used with some success in clinical trials in patients with
severe combined immunodeficiency and viral disorders.
 Few major side effects have been reported, especially with purer
forms produced by genetic engineering. Crude thymic preparations
have produced allergic side effects in some patients.
5-Immune globulin:
 It is isolated from pooled human plasma.
 It is recommended in the treatment of primary humoral
immunodeficiency, congenital agammaglobulinemias, idiopathic
thrombocytopenic purpura, and autoimmune hemolytic anemia.
 The principal side effects are possible anaphylactoid reactions and
severe hypotension.
6-Cytokines :
Lymphokines
 Monokines
 he immune cell function is regulated by cytokines produced by
leukocytes or other supporting cells.
 With the advent of genetic engineering, cytokines can be produced in
pure form and in large quantities.
 Examples of some clinically important cytokines:
a. Interleukin-2 (IL-2)
- It promotes the proliferation, differentiation, and recruitment of
T and B lymphocytes, natural killer cells, and thymocytes.
- Recombinant IL-2 (rIL-2) is administered systemically as an
immunostimulating agent in patients with AIDS and to augment
specific antitumor immunity.

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- Systemic administration of rIL-2 causes fever, nausea, vomiting,
fatigue, and malaise. Other adverse affects include flushing,
diarrhea, chills, rash, edema, symptomatic hypotension, and
certain renal abnormalities.
b. Myeloid Colony–Stimulating Factors
- Recombinant granulocyte-macrophage colony–stimulating factor
(GM-CSF) (Sargramostim) and granulocyte stimulating factor
(G-CSF) (Filgrastim)
- They are cytokines, or growth factors, that support the survival,
clonal expansion, and differentiation of hematopoietic cells.
- In general they are indicated for acceleration of the recovery of
circulating white blood cells in patients who have depressed
hematopoiesis, as a result of either chemotherapy or congential
disorders of hematopoisis.
- Adverse effects include diarrhea, asthenia, rash, malaise, fever,
headache, bone pain, chills, and myalgia. Many of these effects
can be ameliorated by the administration of analgesics and
antipyretics.
c. Interferons
- Interferon-alpha (IFN-α): used clinically in treatment of chronic
hepatitis B and C, leukemias, melanoma.
- Interferon-beta (IFN-β): used clinically in treatment of multiple
sclerosis.
- Interferon-gamma (IFN- γ): used clinically in treatment of chronic
granulomatous disease.

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Unit VIII-Vitamins

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I-Introduction to vitamins importance and sources

Vitamins are a group of unrelated chemical substances that are essential in
small amounts for the regulation of normal metabolism, growth, and
function of the human body.
Not all of the vitamins can be synthesized in the body, and therefore, some
vitamins must be obtained from an external source, such as a proper well
balanced diet or dietary supplements.
Deficiency diseases can result from insufficient vitamin ingestion, irregular
absorption, or impaired metabolic use of these nutrients. Certain groups of
the population are particularly at risk, such as low-income families and
chronically ill patients.
Vitamin toxicity (Hypervitamiosis) can result from ingestion or
administration of excessive quantities of vitamins.
Generally the water-soluble vitamins are less toxic, since excess quantities
are usually excreted in the urine.
Excessive amounts of fat-soluble vitamins, however, are stored in the body,
which makes toxic levels of these vitamins easier to obtain.
Vitamins are usually classified as either fat soluble (vitamins A, D, E, and
K) or water soluble (vitamins B and C).
The fat-soluble vitamins are generally metabolized slowly and are stored in
the liver.
In contrast, the water-soluble vitamins are rapidly metabolized and are
readily excreted in the urine.

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II-Fat-soluble vitamins
A-Vitamin A (Retinol):
1-Sources:
 Animal foods (whole milk, liver, egg yolk, fatty fish and fish liver
oil).
 Plant foods (yellow, green, and orange vegetables and fruit especially
dark green leafy vegetables).
 Plant foods contain the provitamin carotene which converted in the
body into vitamin A.
2-Function:
 Constituent of visual pigments (retinal)

 Maintenance of the functional and structural integrity of epithelial
cells and cartilage
3-Deficiency:
 Night blindness and xerophthalmia,
 Hyperkeratosis and dry skin
 Arthralgia.
4-Toxicity:
 Fatigue
 Headaches
 Skin changes
 Alopecia
 Hepatosplenomegaly
 Teratogenicity.
B-Vitamin D (Calciferol)
 Ergocalciferol (D2)
 Cholecalciferol (D3).
Storage form (25-OH D3) and active form (1,25 (OH)2 D3).
1-Sources:
 Animal food (liver, egg yolk, fatty fish and fish liver oil).
 Others (exposure of the skin to ultra violet rays)

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2-Function:
It increases intestinal absorption of calcium and phosphate.
3-Deficiency:
 Rickets in children (bending bones)
 Osteomalacia in adults (soft bones)
 Hypocalcemic tetany and muscle weakness.
4-Toxicity:
 Hypercalcemia
 Loss of appetite.
C-Vitamin E (Tocopherol)
1-Sources:
 Animal food (liver, egg yolk)
 Plant food (plant oils; including wheat germ, rice, and leafy
vegetables).
2-Function:
Antioxidant .
3-Deficiency:
 Haemolytic anemia
 Areflexia
 Gate disturbance, .
4-Toxicity:
 Muscle weakness
 Fatigue
 Headache, and nausea.
D-Vitamin K (Menadione)
 Phylloquinone (K1)
 Menaquinones (vitamin K2)
 Menadione (K3).

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1-Sources:
 K1: dark green leafy vegetables (e.g. spinach).
 K2: biosynthesis by intestinal flora.
2-Function:
It is essential for the synthesis of proteins that are involved in the
coagulation of blood. The vitamin K–dependent clotting factors II, VII, IX,
X, and protein C and S.
3-Deficiency:
Hemorrhagic conditions
4-Toxicity:
Not been documented.

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III-Water soluble vitamins

A-Vitamin C (Ascorbic Acid)
Sources:
Fresh vegetables and fruits; especially citrus fruits, guava, and strawberries,
green pepper, tomatoes.
Function:
 Antioxidant and coenzyme in oxidation reactions.
 Essential for the maintenance of the ground substance that binds cells
together and for the formation and maintenance of collagen.
Deficiency:
 Scurvy (swollen gums and loose teeth, bruising, poor wound healing,
capillary fragility results in haemorrhages, increased liability to
infection).
Toxicity:
It may result in diarrhoea due to intestinal irritation, renal oxalate stones may
form in some patients.
B-Vitamin B-complex:
 The B vitamin group is made up of substances that tend to occur
together in foods and are given the collective name vitamin B
complex.
 The vitamins of the B group usually have to be converted to an active
form (coenzyme), and most of them play a vital role in intracellular
metabolism.
 The B vitamins are obtained from both meat and vegetable products,
except for vitamin B12, which occurs only in animal products. The
richest source of the B vitamin group is seeds, including the germ of
wheat or of rice.
 The effects of most vitamin B overdoses (toxicity) have not been
documented.

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1-Vitamin B1 (thiamine):
 Function: co-enzyme in carbohydrate metabolism.

 Deficiency:
- Beriberi (oedema, and heart failure, neurological symptoms
such as polyneuritis, anorexia, irritability, and mental
deterioration)
- Wernicke-Korsakoff syndrome (neurological symptoms such as
severe memory deficit, ataxia).
2-Vitamin B2 (Riboflavin):
 Function: co-enzyme in oxidation-reduction reactions.

 Deficiency:
- Ariboflavinosis (angular stomatitis, glossitis, cheilosis, corneal
vascularization, seborrheic dermatitis, peripheral neuropathy).
3-Vitamin B3 (Niacin; Nicotinic acid)
 Derived from tryptophan.

 Deficiency:
- Pellagra (diarrhea, dermatitis, dementia),
- Beefy glossitis.
 Toxicity:
- Flushing
- Pruritus,
- Gastrointestinal disturbances,
- Hepatic toxicity
4-Vitamin B5 (Pantothenate; Pantothenic acid)
 Function: it is an essential component of coenzyme A (CoA) for the

transport of acetyl and succinyl units.
 Deficiency:
- Dermatitis
- Enteritis,
- Alopecia,
- Adrenal insufficiency.

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5-Vitamin B6 (Pyridoxine)
 Function: co-enzyme in amino acid transformations and tryptophan-

niacin conversion.
 Deficiency:
- Neurological symptoms (sensory neuritis, mental depression,
and convulsions)
- Hypochromic sideroblastic anemia.
 Toxicity: peripheral neuropathy.
6-Vitamin B12 (Cobalamin)
 Function: co-enzyme in nucleic acid synthesis and essential for

erythropoiesis.
 Deficiency:
- Pernicious anemia (megaloblastic anemia and neurological
symptoms “peripheral neuropathy, optic atrophy, depression”)
- Glossitis.
C-Folic Acid (Folacin)
Function: co-enzyme in nucleic acid synthesis and protein metabolism and
essential for erythropoiesis.
Deficiency:
 Megaloblastic anemia
 Glossitis
 Diarrhea
 Neural tube defect in fetus.
D-Biotin
Function: co-enzyme in fatty acid synthesis

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Deficiency:
 Anorexia
 Glossitis,
 Depression,
 Dry, scaly dermatitis.
Recommended Daily Dietary All owances a
Fat-Soluble Vitamins
Age VitaminA Vitamin D Vitamin Vitamin

(Years)
or Weight Heigh Protein E K
t
Categor Conditi (kg) (g) RE)b c -
y on (cm) TE)d
Infants 0.0-0.5 6 60 13 375 7.5 3 5
0.5-1.0 9 71 14 375 10 4 10
Childre 1-3 13 90 16 400 10 6 15

n
4-6 20 112 24 500 10 7 20
7-10 28 132 28 700 10 7 30
Males 11-14 45 157 45 1,000 10 10 45
15-18 66 176 59 1,000 10 10 65
19-24 72 177 58 1,000 10 10 70
25-50 79 176 63 1,000 5 10 80
77 173 63 1,000 5 10 80
Female 11-14 46 157 46 800 10 8 45

s
15-18 55 163 44 800 10 8 55
19-24 58 164 46 800 10 8 60

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25-50 63 163 50 800 5 8 65
65 160 50 800 5 8 65
Pregna 60 800 10 10 65
nt
Lactati 1st 6 months 65 1,300 10 12 65

ng
2nd 6 months 62 1,200 10 11 65
Water-Soluble Vitamins
Age Vitami Vitami Vitami

(Years) nC n B6 n B12
or Weig Heig Protei Thiami Riboflavi Niaci Folat
ht ht n n n n e
Conditi
Categor on (kg) (cm) (g) (mg) (mg) (mg) (mg (mg)
y NE)e
Infants 0.0-0.5 6 60 13 30 0.3 0.4 5 0.3 25 0.3
0.5-1.0 9 71 14 35 0.4 0.5 6 0.6 35 0.5
Childre 1-3 13 90 16 40 0.7 0.8 9 1.0 50 0.7

n
4-6 20 112 24 45 0.9 1.1 12 1.1 75 1.0
7-10 28 132 28 45 1.0 1.2 13 1.4 100 1.4
Males 11-14 45 157 45 50 1.3 1.5 17 1.7 150 2.0
15-18 66 176 59 60 1.5 1.8 20 2.0 200 2.0
19-24 72 177 58 60 1.5 1.7 19 2.0 200 2.0
25-50 79 176 63 60 1.5 1.7 19 2.0 200 2.0
77 173 63 60 1.2 1.4 15 2.0 200 2.0
Female 11-14 46 157 46 50 1.1 1.3 15 1.4 150 2.0

s
15-18 55 163 44 60 1.1 1.3 15 1.5 180 2.0
19-24 58 164 46 60 1.1 1.3 15 1.6 180 2.0
25-50 63 163 50 60 1.1 1.3 15 1.6 180 2.0
65 160 50 60 1.0 1.2 13 1.6 180 2.0

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Pregna 60 70 1.5 1.6 17 2.2 400 2.2
nt
Lactati 1st 6 months 65 95 1.6 1.8 20 2.1 280 2.6

ng
2nd 6 months 62 90 1.6 1.7 20 2.1 260 2.6
a The allo wances, expressed as average daily intakes over time, are intended to provide for individual
variations among most normal persons as they live in the Un ited States under usual environmental
stresses. Diets should be based on a variety of common foods in order to provide other nutrients for
which hu man requirements have been less well defined.
b Retinol equivalents (RE -carotene.
c IU of vitamin D.
d -TE). 1 mg d - -TE.
e Niacin equivalents. 1 NE (n iacin equivalent) is equal to 1 mg of n iacin or 60 mg of d ietary tryptophan.

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Unit IX-Locally Acting Drugs

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Skin and Scalp preparations

The patient should be warned that the locally acting agents are for external
use only.
The patient should be told to see his physician if the condition does not
improve and to avoid getting the prepared solution in contact with his eyes.
A-Emolients
They are oily or fatty substances which soften and protect the skin e.g.:
 Fixed oils (vegetable oils)

- Olive oil
- Cotton seed oil,
- Almond oil.
 Fats:
- Lard and wool fat.
 Waxes: they are esters of fatty acids with alcohol.
B-Astringents
They are agents that dry mucous secretions, shrink skin, and cause blanching
(whitening).
Astringents are used to reduce inflammation of mucous membranes, to
promote healing, and to toughen skin.
1-Aluminium acetate tablets:
 When these tablets are added to water, aluminium acetate solution is

prepared.
 This product is used as an astringent for inflammatory skin conditions
such as insect bites, poison ivy, and athlete’s foot.

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2-Calamine lotion (calamine and zinc oxide lotion):
 This product is used as an astringent and as a protectant (used to cover

and protect epithelial surfaces).
 Both these actions aid in reducing inflammation associated with
insect bites, poison ivy, and sunburn.
3-Phenolated and mentholated calamine lotion:
Phenol and menthol have been added to the calamine lotion because they
produce an antipruritic effect.
C-Counter-irritants
 Methyl salicylate (oil of wintergreen).

 Camphor, menthol, and chloroform linimets (alcoholic solution of
volatile oil).
They are irritating agents applied locally to the intact skin to block the deep
pain in muscles or viscera.
Pain stimulus arising from the irritated area of skin will occupy the same
segment of spinal cord that occupied by the deep pain and thus block it.
They also produce dilatation of local blood vessels → increase blood supply
to the affected area.
D-Keratolytics and keratoplastics

Keratolytics are agents that induce sloughing of cornified epithelium (horny
or hard layer of the skin).
Keratoplastic (mild keratolytic) effect is seen when the drug does not
produce a rapid destruction and sloughing, thereby softening the keratin and
loosening the cornified epithelium.
Keratolytic agents are used to remove warts and corns. They are also used in
the treatment of severe acne.

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Keratoplastic agents are used in the treatment of acne, eczema, psoriasis, and
seborrheic dermatitis.
1-Coal tar:
It is used as a keratoplastic in the treatment of eczema, psoriasis, and
2-Salicylic acid:
 It is used as a keratolytic in concentrations from 5% to 20%.

 It is used as a keratoplastic in concentrations from 1% to 2%.
3-Sulfur:
It is used as a keratoplastic in the treatment of acne and seborrheic
dermatitis.
4-Tretinoin (Retin A):
 It is used in the treatment of severe acne.

 The application of this agent to the skin will produce a horny layer of
skin that is more easily removed.
 This medicine should not be applied to windburned or sunburned skin.
It should not be applied to open wounds. Furthermore, the medication
should not be applied inside the nose, around the eyes, or around the
mouth. While the patient is using the medication, he should avoid
exposing the area being treated to too much wind or sun (or sun
lamp).
 Adverse effects of tretinoin include erythema, peeling, burning, and
stinging. These effects often decrease spontaneously with time and are
lessened by use of emollient. Photosensitivity occurs, with a resulting
greater potential for sunburn. Tretinoin, given orally, is highly
teratogenic.

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E-Antiseborrheics:
 Chloroxine
 Selenium sulfide
They are used in the management of dandruff and seborrheic dermatitis.
Seborrheic dermatitis is characterized by a yellowish and greasy scaling of
the scalp and/or mid-parts of the face (around eyebrows and nose) and ears.
The ideal antiseborrheic agent should be nontoxic, relieve pruritus (itching),
modify excessive dryness, and demonstrate wide antifungal and antibacterial
spectra.
The patient should be instructed not to use this medication if blistered, raw,
or oozing areas are present on the scalp and to keep the medication away
from the eyes.
F-Sunscreens:
Acute effects of sun exposure include sunburn and drug-induced phototoxic
reactions. Chronic effects include photoaging and skin cancer.
Sunscreens are topical agents that reduce the amount of ultraviolet radiation
(UVA, UVB) reaching the skin or block it altogether.
Topical sunscreens are divided into physical and chemical agents:
1-Physical sunscreens:
They contain large particulate ingredients that reflect and scatter UVA,
UVB, and visible light. These ingredients include titanium dioxide, talc,
magnesium oxide, zinc oxide, kaolin, ferric chloride, and ichthamnol. These
sunscreens are opaque and therefore frequently cosmetically unacceptable.
2-Chemical sunscreens:
They are transparent and absorb portions of ultraviolet radiation. p-
Aminobenzoic acid esters, cinnamates, and salicylates are effective UVB-
blocking agents. Benzophenones, anthranilates, and particularly

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avobenzone, are effective UVA screens. Multiple chemical sunscreens
usually are combined in commercial products to provide broad-spectrum
coverage. Protection against UVB is more effective than protection against
UVA.
The substantivity of a sunscreen is its resistance to removal by water. A
"water-resistant" sunscreen should continue to function after 40 minutes in
water; a "waterproof" sunscreen withstands 80 minutes in water. The vehicle
is important in determining these properties.
Toxicity:
Contact dermatitis and photocontact dermatitis occur rarely in most
individuals, but they are common in atopic individuals.
The alcohol or fragrance contents of some sunscreen products can be
irritating, which leads to poor compliance by some individuals.
G-Local antiseptics and disinfectants: see before.
H-Miscellaneous agents:
1-Hydroquinone
 Hydroquinone produces reversible depigmentation of the skin by

inhibiting the enzymatic oxidation of tyrosine to 3,4-
dihydroxyphenyalanine and substantial inhibition of other melanocyte
metabolic processes.
 It is indicated for the gradual bleaching of hyperpigmented skin in
conditions such as melasma, freckles, and senile lentigines.
 Exposure to ultraviolet radiation will cause repigmentation, so
hydroquinone is frequently combined with a broad-spectrum
sunscreen.
2-Minoxidil
 Topical minoxidil is the first FDA-approved medication for

stimulating hair growth.
 t is approved for the treatment of androgenetic alopecia in both males
and females.

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 It induces proliferation of epithelial cells near the base of the hair

follicle and may induce vasodilation of scalp blood vessels.
 Allergic contact dermatitis and irritant reactions occur.
3-Topical steroids, antihistamines, antibacterial, antiviral, and antifungal

agents

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II-Drugs used in treatment of psoriasis

Psoriasis is a chronic scaling skin eruption characterized by keratinocyte
hyperproliferation.
A-Acitretin:
 It is a metabolite of the aromatic retinoid etretinate.

 It is given orally in the treatment of psoriasis, especially pustular
forms.
 It probably promotes terminal differentiation in psoriasis by
normalizing expression of keratins by epidermal cells.
 Adverse effects attributable to acitretin therapy are hair loss, initial
cutaneous exfoliation, sticky skin, easy bruising, and liver function
abnormalities. It is also teratogenic.
 Acitretin must not be used by women who are pregnant or may
become pregnant while undergoing treatment or at any time for at
least 3 years after treatment is discontinued.. Patients must not donate
blood during treatment and for 3 years after acitretin is stopped.
B-Tazarotene:
 It is an acetylenic retinoid prodrug that is hydrolyzed to its active form

by an esterase.
 The precise mechanism of action in psoriasis is unknown but may
relate to both anti-inflammatory and antiproliferative actions.
 Adverse local effects include a burning or stinging sensation (sensory
irritation) and peeling, erythema, and localized edema of the skin
(irritant dermatitis). Potentiation of photosensitizing medication may
occur, and patients should be cautioned to minimize sunlight exposure
and to use sunscreens and protective clothing.
 It is absorbed percutaneously, and teratogenic systemic concentrations
may be achieved if applied to more than 20% of total body surface
area. Women of childbearing potential must therefore be advised of
the risk prior to initiating therapy, and adequate birth control measures
must be utilized while on therapy.
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C-Calcipotriene:
 It is a synthetic vitamin D3 derivative.
 Effective in the treatment of plaque type psoriasis vulgaris of
moderate severity
 Adverse effects include burning, itching, and mild irritation, with
dryness and erythema of the treatment area. Care should be taken to
avoid facial contact, which may cause ocular irritation.
D- Psoralens and UVA ( PUVA):

 Photochemotherapy with psoralen and UVA (PUVA) has been
approved for the treatment of vitiligo and psoriasis.
 Psoralen e.g. methoxypsoralen (methoxsalen) is given orally or
applied locally 1 to 2 hours before UVA exposure to produce
photosensitivity.
 The therapeutic effects of PUVA in psoriasis may result from a
decrease in DNA-dependent proliferation after adduct formation.
However, alteration in the immune system caused by PUVA also may
play a role.
 PUVA promotes melanogenesis in normal skin. Pigmentation results
from the transfer of melanosomes from melanocytes to epidermal
cells.
 The major acute side effects of PUVA include nausea, blistering, and
painful erythema.
E-Coal Tar:
Coal tar ointment contains crude coal tar, usually 2% to 5%, dispersed in
petroleum jelly.
 Little is known about its mode of action, which may be related to
antimitotic effects.
 Coal tar has a limited effect when employed as the sole treatment for
psoriasis, and it is now mainly combined with daily UVB irradiation
for this indication (known as the Goeckerman regimen).
 Folliculitis is the primary side effect of coal tar. Irritation and allergic
reactions are rare.

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F-Other drugs in severe cases
 Steroids
 Methotrexate
 Cyclosporin

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Pharmacology II
Contents:
1- Analgesics, Antipyretics and Anti-inflammatory agents
2- Drugs affecting renal and cardiovascular functions
3- Drugs acting on the Blood and Blood Forming Agents
4- Drugs used in Gastro-Intestinal diseases
5- Chemotherapy of Parasitic Infections
6- Chemotherapy of Microbial diseases
7- Antineoplastics and Immunosuppressants
8- Vitamins
9- Locally Acting Drugs

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Unit I- Analgesics, Antipyretics and

Anti-inflammatory agents

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I-The inflammatory response:

Inflammation begins when a stimulus, such as infection, physical or
chemical stress, produces cellular damage.
This damage initiates the chemo-attraction of inflammatory cells, and
activation of these cells to release inflammatory mediators.
A-Inflammatory mediators:
Among the most important inflammatory mediators are:
 Eicosanoids,
 Biological oxidants,
 Cytokines,
 Adhesion factors,
 Digestive enzymes.
B-Phases of the inflammatory response:
 The rapid phase occurs within seconds to minutes and consists of
vasodilatation, increased blood flow, edema and pain. During this
phase, moderate amounts of inflammatory mediators are produced.
 The chronic phase occurs over months to years and is marked by
dramatically increased production of inflammatory mediators.
The need for anti-inflammatory drugs arises when the inflammatory

response is inappropriate, aberrant, sustained, or causes destruction of tissue.

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II-Non steroidal anti-inflammatory drugs (NSAIDs)

A-Mechanism of action:
They exert their action through inhibition of cyclo-oxygenase enzyme
(COX) causing decrease in the formation of inflammatory mediators
(prostaglandins, prostacyclins and thromboxanes).
There are 2 types of COX:
 COX-1: it is the constitutive form, present in many normal tissues.
 COX-2 : it is the inducible form, produced at site of inflammation (not
found in normal tissues)
The pharmacological effects of NSAIDs include:
 Analgesic,
 Antipyretic,
 Anti-inflammatory,
 Antiplatelet effects .
B-Acetylsalicylic acid (Aspirin)
It is the prototype of the NSAIDs.
It is the only NSAD that causes irreversible inhibition of both COX-1 and
COX-2.
Its action is dose dependant.
N.B.: Aspirin is available in all forms. Enteric coated aspirin tablets are less
gastric irritant but slow in absorption
1-Therapeutic uses of Aspirin:
 Antipyretic: in feverish conditions.
 Analgesic & Anti-inflammatory: e.g. headache, toothache,
musculoskeletal disorders as rheumatoid arthritis, rheumatic arthritis
and osteoarthritis.
 Anti-platelet: low dose aspirin is used as a prophylaxis against
thrombo-embolism in angina, myocardial infarction, post angioplasty,
atrial arrhythmia, cerebro-vascular diseases, etc…
 Keratolytic (local salicylic acid): removal of warts & corns.
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2-Adverse effects:
 Gastrointestinal irritation : gastritis, gastric erosions, ulcers, bleeding.
 Hypersensitivity: bronchospasm (aggravation of asthma), rhinitis,
nasal polyps, skin rash.
 Bleeding tendency: due to; decrease platelet aggregation &
prothrombin synthesis.
 Renal impairment: analgesic nephropathy(chronic renal failure with
prolonged use), fluid retention.
 Hepatotoxicity.
 Prolonged labor due to inhibition of uterine contraction.
 Reye’s syndrome: rare, fatal sever hepatic injury associated with
encephalopathy. Occurs if aspirin is used in febrile viral infections in
children less than 12 years.
 Salicylism (low grade aspirin toxicity): vertigo, tinnitus, deafness–
often first signs of toxicity.
3-Aspirin overdose (Acute Toxicity):

Extensions of the toxic actions described above, plus at high doses:
 Vasomotor collapse occurs with respiratory,
 Renal failure,
 Hyperpyrexia,
 Dehydration
 Convulsions.
4-Drug-Drug interactions:
 Antagonizes the uricosuric effects of probenecid and the
antihypertensive effect of antihypertensives (e.g. ACE inhibitors, beta
blockers and loop diuretics).
 Increases the plasma concentration of anticoagulants.

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5-Other salicylic acid derivatives:
 Non acetylated salicylate ( sodium salicylate, magnesium salicylate )
are less gastric irritants but less effective.
 5-aminosalicylic acid ( mesalamine ) is less absorbed and used for
treatment of inflammatory bowel disease(local action).
 Diflunisal: more potent than aspirin, has little antipyretic action, used
mainly for osteoarthritis.
C-Other non-steroidal anti-inflammatory drugs:
They may be better tolerated than aspirin.
1-Non selective COX inhibitors:
They inhibit both COX-1 and COX-2 (as aspirin)
 Acetic acid derivatives:
- Carboxylic acetic acid: Indomethacin, Sulindac, Tolmetin
- Phenyl acetic acid: Diclofinac
 Propionic acid derivatives: Ibuprofen, Ketoprofen, Fenoprofen,
Naproxen, Ketorolac.
 Fenamic acid derivatives: Mefenamic acid, Flufenamic acid
 Pyrazolone derivatives: Azapropazone, Phenylbutazone,
Oxyphenobutazone.
 Oxicams: Piroxicam, Meloxicam, Tinoxicam
2-Selective COX-2 inhibitors:
 Celecoxib,
 Rofecoxib
Their primary differences from other conventional NSAIDs are:
- Less gastrointestinal toxicity.
- Less antiplatelet action.
- They have been withdrawn from market because of cardiovascular
risk

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D-Paracetamol (Acetaminophen):
Inhibition of cyclooxygenases in CNS not in peripheral tissues.
2-Pharmacological effects:
 Analgesic,
 Antipyretic
 No significant anti-inflammatory effect.
3-Comparison with Aspirin:
 No antiplatelet action,
 No bronchospasm,
 Gastrointestinal irritation is minimal,
 Not implicated in Reye syndrome.
4-Adverse effects:
 Hepatotoxicity,
 Nephrotoxicity.
5-Paracetamol overdose (Acute Toxicity):
The toxic metabolites increase causing:
 Nausea,
 Vomiting,
 Diarrhea,
 Abdominal pain
 Hepato-renal failure.
6-Management of Paracetamol Overdose:

N-acetylcysteine within the first 12 hours can protect against toxicity.

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III-Drugs used in treatment of gout

Gout is inflammatory arthritis due to deposition of uric acid crystals in the
joint tissue.
Management of Gout differs between acute attacks and chronic phase.
A-Acute attack:
In acute attacks, drug strategy is reduction of the inflammatory process.
1- Colchicine:
 Decreases release of LTB4,
 Decreases leukocyte migration and phagocytosis.
Adverse effects:
 Diarrhea,
 Abdominal pain.
 Prolonged use may cause hematuria, alopecia, myelosuppression and
peripheral neuropathy.
2- Indomethacin and other NSAIDs (Sulindac, Naproxen)
3- Intra-articular steroids.
B-In-between attacks (chronic gout)
Drug strategy is reduction of the uric acid pool.
1-Decrease uric acid synthesis:
 Allopurinol
Inhibits xanthin oxidase enzyme → ↓ uric acid synthesis.
Adverse effects:
- GIT disturbance,
- Peripheral neuropathy,
- Vasculitis,
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- Skin rash.
2-Increase uric acid excretion (uricosuric drugs):
 Probenecid
 Sulfinpyrazone
In large doses, they inhibit proximal tubular reabsorption of urate
(uric acid retention in small dose).
Adverse effects:
- GIT disturbance,
- Nephritic syndrome,
- Skin rash.
They action of uricosuric drugs is antagonized by salicylate .

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Unit II- Drugs affecting renal and

cardiovascular functions

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I-Diuretics
A-Review on Renal physiology:
The kidneys form urine from blood plasma. Blood flow through the kidneys is a
major factor in determining urinary output.
Glomerular filtration is the first step in urine formation. Filtration is not selective
in terms of usefulness of materials; it is selective only in terms of size.
Tubular reabsorption is selective in terms of usefulness. Nutrients such as glucose,
amino acids, and vitamins are reabsorbed from the filtrate in the renal tubules to
the blood in the peritubular capillaries.
Tubular secretion takes place from the blood in the peritubular capillaries to the
filtrate in the renal tubules and can ensure that wastes such as creatinine or excess
H+ ions are actively put into the filtrate to be excreted in urine.
Hormones involved in the formation of urine lead to concentration of the urine:
 Antidiuretic hormone ADH: increase water reabsorption in distal and
collecting tubules.
 Aldosterone: increases sodium reabsorption in the distal tubules and
collecting ducts.
B-Carbonic Anhydrase Inhibitors
 Acetazolamide,
 Dorzolamide
They inhibit Carbonic Anydrase enzyme→ loss of sodium and bicarbonate
in urine→ self-limited alkaline diuresis.

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2-Site of action:
proximal convoluted tubule.
3-Clinical use:
 Glaucoma(↓intraocular pressure),
 Metabolic alkalosis
 Urinary alkalinization.
4-Adverse effects:
 Neuropathy,
 Acidosis,
 Hypokalemia,
 Hyperchloremia.
C-Osmotic diuretics:
 Mannitol (given IV)
↑tubular fluid osmolarity → ↑urine flow.
2-Site of action:
Entire tubule.
3-Clinical use:
 Glaucoma,
 ↓intracranial pressure,
 Acute renal failure.
4-Adverse effects:
 Pulmonary edema,
 Dehydration.
Osmotic diuretics are Contraindicated in Anuria and CHF.

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D-Loop diuretics:
 Furosemide ,
 Bumetanide ,
 Ethacrynic acid
Inhibits Na/K/2CL cotransport system of thick ascending limb of loop of
Henle→↓ Na & CL reabsorption
2-Site of action:
Ascending limb of loop of Henle
3-Clinical use:
 Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary
edema),
 Hypertension,
 Hypercalcemia
4-Adverse effects:
 Ototoxicity
 Allergy
 Hypovolaemia
hypomagnesaemia, hypocalcaemia),
 Hyperuricaemia
 Hyperglycaemia

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E-Thiazides:
 Chlorothiazide,
 Hydrochlorothiazide,
 Indepamide
They inhibit NaCl reabsorption.
2-Site of action:
Early distal convoluted tubule.
3-Clinical use:
 Edematous states,
 Hypertension,
 Renal calcium stone,
 Nephrogenic diabetes insipidus.
4-Adverse effects:
 Allergy
 Hypovolaemia
 NO ototoxicity
hypomagnesaemia, hypercalcaemia),
 Hyperuricaemia
 Hyperglycaemia
F- K-sparing diuretics:
 Aldosterone receptor antagonist: Spironolactone
 Non-Aldosterone receptor antagonist:
- Triamterene,
- Amiloride
↓ Na reabsorption by:
 Spironolactone: Competitive aldosterone receptor antagonist.
 Triamterene, Amiloride: block Na channels.

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2-Site of action:
Collecting tubule
3-Clinical use:
 K depletion, with other drugs in CHF and Hypertension.
 Spironolactone used in hyperaldosteronism
4-Adverse effects:
 Hyperkalemia,
 Acidosis,
 Spironolactone has anti-androgen effect (e.g. Gynecomastia)
G-Acidifying Salts:
 Ammonium chloride
It causes acidification of urine with excretion of NaCl in urine→ diuresis.
2-Clinical use:
Used to acidify urine & in treatment of alkalosis.

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pharmacology
II-Drugs used in the treatment of congestive heart

failure (CHF)
Heart failure is a condition in which cardiac output is less than the body
needs.
Drugs used in the treatment of CHF are positive Inotropic drugs,
cardioglycosids, diuretics and Vasodilators
A-Cardiac Glycosides:
Digitoxin Digoxin Ouabain

Oral more less 0
bioavailability
Duration of longer shorter shortest
action
Rout of hepatic (so, preferred in renal renal renal
elimination impairment)
Administration oral oral, IV IV
They increase free Ca concentration within the cardiac cells→↑ contractility.
2-Clinical use:
 Heart failure (digitoxin or digoxin in chronic HF & ouabain or

digoxin in acute cases),
 Supraventricular arrhythmia

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3-Adverse & toxic effects:
 Nausea,
 Vomiting,
 Diarrhea.
 Blurry yellow vision,
 Arrhythmias.
4-Toxicities of digoxin are increased by:
 Renal failure,
 Hypokalemia,
 Hypomagnesaemia,
 Hypocalcaemia
 Drug Interaction with quinidine, verapamil, sympathomimetics and
some antibiotics(e.g., erythromycin) .
5-Specific Antidote:
Anti-digitalis Fab fragments
6-Management of toxicity:
 Slowly normalize K+,
 Lidocaine,
 Cardiac pacer,
 Anti-dig Fab fragments.
B-Other Inotropic drugs:
1-β1 agonist:
 Dobutamine, used in acute heart failure (IV drip.).
 Prenalterol, used in chronic heart failure (oral).
 Dopamine, used in resistant heart failure & cardiogenic shock (IV
drip.).
They Stimulate β1 receptors in the heart→↑ contractility.

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2-Phosphodiestrase inhibitors (PDE inhibitors):
 Bibpyridines used in for short term treatment of H.F (IV).
- Amrinone
- Milrinone)
 Methylxanthines (Aminophylline) used in acute H.F. with pulmonary
edema ( slow IV)
Mechanism of action :
Inhibit PDE→↑cAMP→↑ contractility.

C) Vasodilators:
 Angiotensin converting enzyme inhibitors:
- Captopril ,
- Enalapril ,
- Lisinopril
 Calcium channel blockers:
- Amlodipine
 Other vasodilators:
- Hydralazine ,
- Nitroprusside
↓ Peripheral resistance→ ↓ after load→ ↑Cardiac output.
D-Diuretics:
↓ Blood volume→ ↓ venous return→ ↓ preload→ ↑Cardiac output.

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III-Drugs used in the treatment of Arrhythmia

A-Cardiac electro-physiology:
Myocardial action potential and ionic movement occur in atrial and
ventricular myocytes and Purkinje fibers.
 Phase 0 = rapid depolarization; voltage-gated Na channels open
(rapid Na influx).
 Phase 1 = initial repolarization; voltage-gated K channels begin to
open
(K efflux).
 Phase 2 = “plateau” sustained depolarization; voltage-gated Ca

channels open (slow Ca influx).
 Phase 3 = rapid repolarization; voltage-gated slow K channels open
(rapid K efflux).
 Phase 4 = gradual return to resting potential; Na leaves the cell in
exchange with K.

pharmacology
1-The Heartbeat:
The electrical impulse that triggers a normal cardiac contraction originates at
regular intervals in the sinoatrial node (SAN), usually at a frequency of 60–
100 beats per minute.
This impulse spreads rapidly through the atria and enters the atrioventricular
node (AVN), which is normally the only conduction pathway between the
atria and ventricles.
Conduction through the atrioventricular node is slow, requiring about 0.15 s.
(This delay provides time for atrial contraction to propel blood into the
ventricles.) The impulse then propagates over the His-Purkinje system and
invades all parts of the ventricles. Ventricular activation is complete in less
than 0.1 s; therefore, contraction of all of the ventricular muscle is
synchronous and hemodynamically effective.
2-Control of the SA Node and AV Node.
Both the SA and the AV node are controlled by the autonomic nervous
system.
Parasympathetic stimulation, supplied by the vagus nerve tends to decrease
both the rate and force of contraction of the heart.
Sympathetic stimulation, serves to increase both the rate and force of
contraction of the heart. The predominant sympathetic receptor is a beta-
receptor although it has been shown that a small amount of alpha-receptors
are present in the heart.

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B-Definition and Classification of arrhythmia:
Arrhythmia is a term that is used to refer to any abnormal heartbeat
(Disorders of impulse formation, impulse conduction, or a combination)
1-Classification:
 Tachyarrhythmia:
- Supraventricular :
o Supraventricular tachycardia.
o Atrial flutter.
o Atrial fibrillation (AF)
- Ventricular arrhythmia:
o Ventricular tachycardia
o Ventricular flutter
o Ventricular fibrillation
 Bradyarrhythmia :
- Sinus bradycardia.
- Nodal rhythm.
- Heart block (partial & complete).
C-Antiarrhythmic drugs
The general mechanism of action for all these drugs is to suppress abnormal
beats or restore normal cardiac rhythm by depressing various properties of
the myocardium.
1- Class I (Na+ channel blockers):
They decrease the rate of rise of phase 0 of the action potential decrease
amplitude of action potential.
According to duration of action potential they are subclassified into:
 Class IA
- Quinidine ,
- Procainamide ,
- Disopyramide
Adverse effects:

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- Quinidine: cinchonism (headache, tinnitus, deafness, visual
disturbances), thrombocytopenia, hypotension, nausea,
vomiting.
- Procainamide: SLE-like syndrome
- Disopyramide: heart failure.
 Class IB
- Lidocaine IV
- Phenytoin
They decrease action potential duration.
Adverse effects:
- Lidocaine: local anesthetic, CNS stimulation/depression,
hypotension and myocardial depression.
 Class IC
- Flecainide ,
- Encainide
No effect on action potential duration.
Adverse effects:
High potential for proarrhythmia (new arrhythmias).
2- Class II (β blockers)
 Propranolol ,
 Atenolol ,
 Sotalol
They suppress abnormal pacemakers by reducing the slope of spontaneous
depolarization (phase 4). Decrease SAN and AVN activity.
Adverse effects:
- Impotence,
- Exacerbation of asthma,
- CV effects (bradycardia, AV block, CHF), CNS effects (sedation,
sleep alterations).
- They may mask the signs of hypoglycemia.

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3- Class III (K+ channel blockers)
 Amiodarone ,
 Bretylium,
 Sotalol
Adverse effects:
- Amiodarone: pulmonary ﬁbrosis, corneal deposits, thyroid
dysfunction.
- Bretylium : new arrhythmias, hypotension.
- Sotalol: excessive β block.
4- Class IV (Ca2+ channel blockers)
 Verapamil
 Diltiazem.
They slow conduction velocity of atrioventricular node.
Adverse effects:
- Constipation,
- Flushing,
- Edema,
- CV effects (CHF, AV block, sinus node depression)
5- Unclassified
 Adenosine: slow conduction in accessory conducting pathway.
 Digoxin: slow conduction of atrioventricular node.
 Atropine: muscarinic blocking action.
 Adrenaline & Isoprenaline: sympathomimitic action.
D-Therapeutic indication of antiarrhythemic:
1- Supraventricular tachyarrhythmia:
 Class IV,
 Adenosine,
 Digoxin

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2- Ventricular tachyarrhythmia:
 Class IB
3- Supraventricular &Ventricular tachyarrhythmia:

 Class IA,
 Class IC,
 Class II,
 Class III
4- Bradyarrhythmia:
 Atropine,
 Adrenaline
 Isoprenaline

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IV-Drugs used in treatment of angina

Angina pectoris is an acute chest pain that occurs when coronary blood flow
is inadequate to supply the oxygen required by the heart.
A-Types of angina:
 Classic angina(angina of effort or exercise): is due to coronary
atherosclerotic occlusion
 Vasospastic or variant (Prinzmetal) angina: is due to a reversible
decrease in coronary blood flow.
 Unstable angina (crescendo): presents as an acute coronary syndrome
with platelet aggregation.
B-Drug strategies in classic and vasospastic angina:

 O2 requirements
 O2 supply
1-During the acute attack:

 Short acting Nitrates :
- Glyceryl Trinitrate (Nitroglycerin) (sublingual, I.V. Infusion)
- Amyl nitrite (Inhalation)
- Isosorbide dinitrate (Sublingual)
2-In between the attacks:
 Long acting Nitrates
- Isosorbide mononitrate -oral-
- Isosorbide dinitrate (Oral )
 Beta adrenergic blockers
 Calcium channel blockers
 Antiplatelets e.g. (aspirin, dipyridamol): used to  incidence of
coronary thrombosis.

pharmacology
Drug strategies Nitrates Calcium Beta blockers
channel
blockers
cardiac O2 venodilatation heart rate, force of contraction
requirements peripheral venous return and cardiac output
arteriodilataion
arteriodilataion peripheral
peripheral vascular vascular resistance
resistance
cardiac O2 supply Coronary vasodilatation
Adverse effects of Nitrates:
The major acute toxicities of organic nitrates are direct extensions of
therapeutic vasodilatation:
- Orthostatic hypotension,
- Tachycardia
- Throbbing headache.
Nitrates Tolerance:
Tolerance for the vasodilating action may develop with continuous exposure
to nitrates without interruption.
C-Drug strategies in unstable angina:
 Combination of Nitrates with Beta blockers used initially with
supplemental oxygen.
 To prevent thrombosis (and myocardial infarction): heparin,
warfarine, and antiplatelets.

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V-Antihypertensive drugs
A-Sympathoplegics
1-Centrally acting Alpha 2 agonist:
Methyldopa Clonidine
Mech. Of Activate α2 receptors in the medulla→ ↓central sympathetic
action outflow
Adverse Sedation, dizziness, sexual Sedation, dry mouth , edema,
effects dysfunction, positive severe rebound hypertension
Coombs’ test
Comments Safe in renal dysfunction and
pregnancy
2-Adrenergic neuron blockers:
Reserpine Guanethidine
Mech. of Destruction of storage Binds to storage granules→ inhibit
action granules→ ↓NE NE release
Adverse Sedation, depression, Orthostatic hypotension, fluid
effects diarrhea. retention, sexual dysfunction
,diarrhea
3-Alpha blockers:
 Mech. of action : α1 blocking→ vasodilatation →↓peripheral
resistance
 Selective α1-receptors blockers:
- Prazosin ,
- Terazosin
- Doxazosin.
- First-dose orthostatic hypotension,
- Dizziness,
- Headache.

pharmacology
 Used also in benign prostatic hyperplasia to decrease urinary
retention.
 N.B. non selective α blockers cause reflex tachycardia; so there use
has diminished after the development of drugs that are relatively
selective for α1-receptors.
4-Beta blockers:
 Mech. of action: β1 blocking→ ↓cardiac output & ↓renin secretion.
 Selectivity:
- Nonselective: propranolol, timolol, pindolol.
- Cardio selective(β1 selective): atenolol, esmolol,metoprolol.
N.B. labetalol (blocks α1 & β receptors-used in
pheochromocytoma)
 Adverse effects :
- Impotence,
- Cardiovascular adverse effects (bradycardia, AV block,
CHF),
- CNS adverse effects (sedation, sleep alterations),
- Non selective drugs may cause exacerbation of asthma.
B-Direct acting vasodilators
Hydralazine Minoxidil Diazoxide Nitroprosside
Mech. of arteriolar dilatation arteriolar dilatation (open K Mixed veno-
action (relax smooth ms. channels in the arterioles) arteriolar dilatation
of arterioles)
Adverse lupus-like Hypertrichosis, Hyperglycemia, Cyanide
effects syndrome, tachycardia, tachycardia, accumulation →
tachycardia, fluid retention fluid retention cyanosis, muscle
fluid retention spasms, psychosis
(with prolonged
therapy),
tachycardia,
fluid retention
Comments Used orally in moderate to severe Used I.V for hypertensive
cases emergencies

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C-Calcium channel blockers (CCBs)
block Ca channels→↓intracellular Ca.
In cardiac muscle→↓contractility→↓cardiac output.
In blood vessels →vasodilatation.
 Selectivity:
- More selective on heart: Verapamil & Diltiazem
- More selective on blood vessels: Nifedipine & Amlodipine
- Constipation ,
- Nausea.
- Heart failure ,
- Heart block (Verapamil & Diltiazem)
tachycardia , flushing (Nifedipine)
D-Drugs affecting angiotensin system
1-Angiotensin converting enzyme inhibitors (ACE Is):
 Captopril
 Enalapril
 Lisinopril
 Mechanism of action:
- Prevent Angiotensin II formation → prevent activation of
AT-1 receptors→ ↓vasoconstriction &↓ aldosterone
secretion→mixed vasodilatation.
- Inhibit the metabolism of bradykinin→vasodilatation.
- Cough,
- Angioedema,
- Proteinuria,
- Taste changes,
- Hypotension,
- Pregnancy problems (fetal renal damage),
- Rash, immune reactions,
- Hyperkalemia.

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2-Angiotensin-1 receptors antagonists (AT-1 antagonists):
 Losartan
 Irbesartan
 Candesartan
- Prevent activation of AT-1 receptors→………
-
 Adverse effects: as ACEIs but without cough .
E-Diuretics:
1-Mechansim of action:
- ↓blood volume→↓cardiac output .
- vasodilator effect: direct effect & by ↓vascular sensitivity to
vasopressor agents → ↓peripheral resistance.
2-Selection:
 Thiazide diuretics: initial therapy in most cases, used in mild to
moderate hypertension.
 Loop diuretics: in sever and malignant hypertension and
hypertension of renal failure.
 K-sparing diuretics: in hyperaldosteronism.
F-Antihypertensive drugs in special cases

Indication Suitable drugs
Angina Beta blockers , CCBs
Heart failure ACE Is , AT-1 antagonists
Diabetes ACE Is , AT-1 antagonists
Dyslipidemias Alpha blockers , CCBs
BPH Alpha blockers

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VI-Drugs used in the treatment of Hyperlipidemia

Hyperlipidemia is a condition of high levels of cholesterol, triglycerides, and
/or lipoprotein in the blood.
Drug Effect on Effect on Effect on Side

LDL “bad HDL “good triglycerides effects/problems
cholesterol” cholesterol”
Bile acid ↓↓ No effect Slight ↑ gastrointestinal
sequestrants upset ,
(Resins) ↓absorbption of
e.g. fat soluble
cholestyramine, vitamins,
colestipol digoxin and
thiazides .
HMG-CoA ↓↓↓ ↑ ↓ gastrointestinal
reductase upset ,
inhibitors myopathy
(Statins) (muscle aches
e.g. lovastatin, and weakness)
pravastatin,
simvastatin,
atorvastatin
Nicotinic acid ↓↓ ↑↑ ↓ gastrointestinal
and its upset , pruritus
derivatives ,facial redness
and flushing
(↓by aspirin or
long-term use)
Lipoprotein ↓ ↑ ↓↓↓ gastrointestinal
lipase upset ,
stimulators myopathy ,
(Fibrates) gallstones,
e.g.
gemfibrozil,
clofibrate

pharmacology
Antihyperlipidemic agents may prevent cholesterol synthesis or promote the

breakdown of internal cholesterol.
LDL = low density lipoprotein
HDL = high density lipoprotein
HMG-CoA = Hydroxy Methyl Glutaryl -CoA

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Unit III- Drugs acting on the Blood and

Blood Forming Agents

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I-Drugs for iron deficiency anaemia:

A-Physiology:
Iron is required for haemoglobin production. Absence of adequate iron
leads to microcytic hypochromic anaemia (iron deficiency anaemia).
Total body iron: 3.5 gm (2/3 in Hb & 1/3 in ferritin, myoglobin,
haemosidren and enzymes).
 Daily requirement: 10-15 mg of which 10% is absorbed.
 Main dietary source: meat & liver.
Etiology:
 ↓ intake:
- starvation,
- anorexia.
 ↓ absorption:
- gastrectomy,
- malabsorption syndrome and excess phytate, phosphate e.g.
cereals, tannic acid e.g. tea.
 ↑ requirements:
- pregnancy,
- lactation,
- after hemorrhage.
 ↑ loss:
- chronic blood loss (e.g. ankylostoma, chronic GIT bleeding)
B-Iron therapy:
1-Oral iron (Iron salts):
 Ferrous sulfate,
 Ferrous gluconate,
 Ferrous succinate
 Ferrous fumarate.
They should be in ferrous form (ferric form is unabsorbable)
Duration of treatment should be 3-6 months to replenish iron store.

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Side effects:
- Nausea,
- Vomiting,
- Epigastric discomfort,
- Abdominal cramps with diarrhea or constipation,
- Black staining of the teeth & stool.
2-Parenteral iron:
 Iron dextran complex,
 Iron sorbitol
They are indicated if patient not tolerated or not absorbing the oral iron.
Side effects:
- Local pain
- Brownish discoloration of the tissue at site of injection,
- Fever,
- Headache,
- Arthralgia,
- Anaphylactic shock
Antidote for toxicity:Desferoxamine.

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II-Drugs for Megaloblastic anaemia:

A-Physiology:
Vitamin B12 and folic acid are essential for normal DNA synthesis.
Deficiency of either of them results in impaired production and abnormal
maturation of erythroid precursor cells, giving rise to megaloblastic anaemia.
Vitamin B12 deficiency due to a lack of gastric intrinsic factor results in
pernicious anemia. This type of megaloblastic anaemia causes neurological
damage if it is not treated.
Daily requirement:
 B12 → 1 mcgm,
 Folic acid → 1 mg
Main dietary source:

 B12 → animal products,
 Folic acid → vegetables
B-Aetiology:
B12 deficiency Folic acid deficiency

↓ intake Vegetarians, Lack of vegetable intake,
starvation, anorexia starvation, anorexia
↓ absorption Gastrectomy, pernicious malabsorption syndrome,
anemia(absent intrinsic drugs: anticonvulsant e.g.
factor), malabsorption barbitone, folic antagonists e.g.
syndrome methotrxate
↓ utilization Lack of transcbalamin II Methotrexate, trimethprim
↑ requirements pregnancy, lactation pregnancy, lactation, hemolytic
anemia, hemodialysis

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C-Vitamin B12 therapy:
It is given parenteral.
 Cyanocobalamine,
 Hydroxycobalamine
D-Folic acid therapy:
 Folic acid (Oral),
 Folinic acid (Parenteral).
Treatment of Vitamin B12 deficient megaloblastic anemia with folic acid
alone may improve the symptoms; however, neurological damage may still
occur if vitamin B12 intake is not supplemented.

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III- Anti-coagulants for Homeostasis

Homeostasis involves the interplay of three phases (vascular, platelet, and
coagulation).
The end result of these phases are, vasoconstriction, platelets aggregation )
platelet plug) at site of injury, and formation of fibrin clot (coagulation) to
prevent blood loss.
The fibrinolytic system prevents propagation of clotting beyond the site of
vascular injury and is involved in clot dissolution, or lysis.
A-Mechanism of Platelets aggregation :
 Platelet adhesion to site of vascular injury.
 Platelet activation by collagen, ADP, thrombin, TXA2, 5HT →
increase expression of glycoprotein IIb/IIIa receptors on platelets
surface.
 Platelets aggregation by a cross-linking reaction due to fibrinogen
binding to glycoprotein IIb/IIIa receptors.

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B-Mechanism of blood coagulation:

Blood coagulates by the transformation of soluble fibrinogen into insoluble
fibrin.
Several circulating proteins interact in a cascading series of limited
proteolytic reactions.
At each step, a clotting factor (e.g., factor VII becomes an active protease
(e.g., factor VIIa) and activates the next clotting factor until finally a solid
fibrin clot is formed.
This process occurs in two interrelated pathways, the intrinsic (inside blood
vessels) and extrinsic (inside tissues); both converge on a common pathway
that leads to the activation of factor X.
Several of the bloods clotting factors are targets for drug therapy.

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C-Anti-coagulant drugs:
They are drugs which inhibit the development and enlargement of clots by
actions on the coagulation phase.
They do not lyse clots or affect the fibrinolytic pathways.
1-Heparin and LMWH:
 Standard heparin: a mixture of sulphated polysaccharides.

 Low-molecular-weight heparins (LMWH)
- Enoxaparin,
- Dalteparin,
- Ardeparin,
- Tinzaparin:

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They have better bioavailability, longer half-life, less
thrombocytopenia and greater factor Xa specificity than standard
heparin.
They can be administered subcutaneously and without laboratory
monitoring.
 Danaproid: a heparin of different structure. It has greater factor Xa
specificity than LMWH . Bleeding due to it is not reversed by
protamine. It may be safer in hypersensitivity to heparin.
2-Oral Anti-coagulants
 Coumarins (warfarin)
 Drug interaction with oral anticoagulants:
- Actions increased by aspirin, cimetidine, metronidazole,
sulfonamides.
- Actions decreased by vitamin K, barbiturates, carbamazepine,
cholystramine, rifampin, thiazides

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Heparins Warfarin
(oral anticoagulants)
Chemical Large water-soluble Small lipid-soluble molecule
nature polysaccharide
Rout of Parenteral (IV, SC) Oral
administration
Site of action Blood Liver
Onset of Rapid (seconds) Slow, limited by half-lives of
action normal clotting factors
Mechanism of Activates antithrombin III, Impairs the hepatic synthesis
action resulting in the inactivation of vitamin. K–dependent
of several clotting factors clotting factors II, VII, IX,
(especially IIa & Xa). and X (vitamin K
Action in vivo & in vitro. antagonist). Action in vivo
only.
Duration of Acute (hours) Chronic (weeks or months)
action
Clinical use Rapid anticoagulation Long-term anticoagulation
(intensive) for thromboses, (controlled) for ……
emboli, stroke, angina, Not used in pregnant women
Myocardial Infarction, (can cross the placenta).
DVT. Used during
pregnancy (does not cross
placenta)
Monitoring Partial thromboplastin time Prothrombin time PT
PTT (intrinsic pathway) (extrinsic pathway)
Toxicity Bleeding, Bleeding, teratogenic, drug–
thrombocytopenia, drug interactions
hypersensitivity,
osteoporosis.
Antagonist Protamine sulfate IV vitamin K and fresh
frozen plasma

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D-Fibrinolytic drugs
They are also called thrombolytics, drugs which dissolve the thrombus by
formation of the fibrinolytic plasmin from plasminogen.
1-Non-Fibrin selective (Non selective fibrinolytics):
 Urokinase.
 Streptokinase.
 Anistreplase (Anisooylated plasminogen streptokinase activator
complex (APSAC) ).
They Act on both fibrin-bound and free(circulating)plasminogen →
fibrinolysis →dissolve the thrombus,
systemic fibrinogenolysis →generalized hypo-coagulabiliy state .
2-Fibrin selective (Selective fibrinolytics):
 Recombinant human tissue-type plasminogen activator (rt-PA):
- Alteplase,
- Reteplase,
- Tenecteplase
 Recombinant single chain urokinase plasminogen activator (rscu-PA).
They Act mainly on fibrin-bound plasminogen → fibrinolysis →dissolve
the thrombus
They are less liable to cause coagulation disturbance.
3-Clinical uses of fibrinolytic drugs:
 Coronary artery thrombosis in myocardial infarction: they decrease
mortality by >60% if used within 3 hours.
 Non coronary thrombosis:
- Deep venous thrombosis,
- Pulmonary embolism,
- Occular thrombosis.

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4-Side effects of fibrinolytic drugs:
 Bleeding,
 Hypersensitivity reaction (streptokinase & APSAC)
5-Antidote in excessive bleeding:
Antifibrinolysins
 Aminocaproic acid
 Tranxamic acid
E-Anti-platelet drugs
They are drugs which inhibit platelet aggregation and so, inhibit the clot
formation.
1-Aspirin:
The prototype anti-platelet drug.
It irreversibly inhibits COX in platelets→↓ TXA2 →↓activation,
2-ADP receptor blockers:
 Ticlopidine
 Clopidogrel:
They block ADP receptors on platelets→ ↓activation,
Ticlopidine has risk of causing sever thrombocytopenia & neutropenia

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3-Antagonists of Glycoprotein IIb/IIIa:
 Abciximab,
 Eptifibatide,
 Tirofiban:
They are antagonists that bind to glycoprotein IIb/IIIa receptors→
↓aggregation by preventing cross-linking reaction.
4-Dipyridamole:
Inhibition of PDE →↑cAMP in platelets→ ↓aggregation
N.B.: largely ineffective when used alone
5-Clinical uses of anti-platelet drugs:
As a prophylaxis against:
 Thrombo-embolism in angina,
 Myocardial infarction,
 Post angioplasty,
 Atrial arrhythmia,
 Cerebro-vascular diseases, etc…
F-Fibrinolytic inhibitors (Antifibrinolytics)
 Tranexamic acid.
 Aminocaproic acid.
They are drugs which inhibit fibrinolysis by inhibition of plasminogen
activation.
Clinical uses:
 Antidote for fibrinolytic drugs.
 Control bleeding following surgery.
 Hemophiliac patients, to control bleeding after minor trauma or
surgery.

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Unit IV- Drugs used in Gastro-

Intestinal diseases

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I-Gastric secretion
A-Regulation of acid secretion:
Phases of acid secretion in response to food:
1-Cephalic Phase 2-Gastric Phase 3-Intestinal
Phase
Stimulant Psychic e.g. smell, Food in stomach Acid chime in
taste, sight, or (antral the duodenum
discussion of food distention)
Mediated Acetylcholine (Vagus Gastrin hormone Entrogastrone
through nerve) hormone
Effect on acid ↑↑↑ ↑↑↑ ↓↓↓
secretion
B-Role of acetylcholine, histamine and gastrin:

Acetylcholine and Gastrin stimulate the enterochromaffin-like (ECL) cells to
release histamine.
The parietal cell contains receptors for acetylcholine(M3), histamine(H2)
and gastrin. When they bind to the parietal cell receptors, they stimulate acid
(hydrogen ion) secretion by the H /K ATPase (the proton pump) on the
canalicular surface.

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II-Drugs used in treatment of gastric ulcer:

A-H2-receptor antagonists:
 Cimetidine,
 Ranitidine,
 Nizatidine
 Famotidine
They inhibit basal and meal-stimulated gastric acid secretion.
Cimetidine is less potent and has more adverse effects than the other drugs.
2-Adverse effects:
Cimetidine rarely produces side effects such as mental status changes
(confusion, hallucinations, agitation) and antiandrogenic effects
(gynecomastia, decreased libido or impotence in men and galactorrhea in
women).

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 Cimetidine inhibits activity of hepatic enzyme cytochrome P450
decrease metabolism of other drugs such as warfarin, phenytoin,
several benzodiazepines, ß-blockers, Ca channel blockers, tricyclic
antidepressants, metronidazole, etc.
 Unlike cimetidine, its newer and more potent congeners, ranitidine,
nizatidine, and famotidine, have no antiandrogenic effects and do not
interfere with the hepatic biotransformation of other drugs.
B-Proton pump (H /K ATPase) inhibitors:
 Omeprazole,
 Lansoprazole,
 Pantoprazole,
 Rabeprazole
 Esomeprazole
They totally block basal and meal-stimulated gastric acid secretion (more
effective than H2-receptore antagonists in inhibition of acid secretion)
2-Adverse effects:
 GI disturbance (indigestion, diarrhea and colic).
 Enteric infections (eg,salmonella, shigella) from ingestion of bacteria
due to decrease acidity.
 Gastric carcinoid tumors have developed in rats but not in human after
long-term use.
 Decrease absorption of vit B12 and minerals (iron, calcium, zinc)
from food due to decrease acidity.
 They decrease absorption of drugs for which gastric acidity affects
bioavailability e.g. digoxin, quinolones, ketaconazole.
 Omeprazole decrease activity of cytochrome P450 decrease
metabolism of warfarin, phenytoin and diazepam.

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C-Antacids:
 Absorbable:
- NaHCO3
 Non-absorbable:
- CaCO3,
- Al(OH) 3,
- Mg salts (e.g. Mg(OH)2 and Mg trisilicate)
1-Mechanism of Action:
They neutralize gastric acidity.

2-Adverse effects:
They can affect absorption, bioavailability, or urinary excretion of other
drugs by altering gastric and urinary pH or by delaying gastric emptying.
Hence, antacids should not be given within 2 hours of doses of tetracyclines,
digoxin, quinolones and ketaconazole.
Overuse can also cause the following problems:
 Sodium bicarbonate NaHCO3:
- Alkalosis,
 Calcium carbonate CaCO3:
- Constipation,
- Hypercalcemia
 Aluminum hydroxide Al(OH) 3:
- Constipation
- Hypophosphatemia .
 Magnesium salts:
- Diarrhea
- Hypermagnesemia
 All can cause hypokalemia

pharmacology
D-Drugs that protect mucosa
1-Sucralfate (Aluminum sucrose sulfate)
Action:
It polymerizes in the acid environment of the stomach and selectively binds
necrotic peptic ulcer tissue, creating a protective layer against acid and
pepsin.
Adverse effects:
- It may cause constipation due to the aluminum salt.
- It may bind to other medications, impairing their absorption
(e.g. tetracyclines, digoxin, quinolones and ketaconazole).
2-Prostaglandin Analogs: Misoprostol
Misoprostol is PGE1 analog. It increases production and secretion of gastric
mucous barrier.
Adverse effects: Diarrhea.
It is contraindicated in women of childbearing potential (abortifacient).
3-Colloidal Bismuth Compounds:
 Bismuth subsalicylate
 Bismuth subcitrate
 Bismuth dinitrate
Mechanism of Action:
- Like sucralfate, it coats ulcers and erosions, creating a protective layer
against acid and pepsin.
- It may also stimulate prostaglandin, mucus, and bicarbonate secretion.
- Bismuth has direct antimicrobial activity against H pylori.
Adverse effects: blackening of the tongue and stool.
Prolonged usage may rarely lead to bismuth toxicity resulting in
encephalopathy (headaches, confusion, seizures).

pharmacology
4-Carbenoxolone:
It is a derivative of glycyrrhetinic acid, which occurs in the sap of licorice
root. It stimulates prostaglandin and mucus secretion (aldosteron like
action).
Adverse effects:
Hypokalemia and Na retention (aldosteron like effect)  oedema and

hypertension.
III-Drugs used to eradicate Helicobacter pylori bacteria

This microorganism plays an important role in the pathogenesis of
chronic gastritis and peptic ulcer disease.
Triple therapy: four times daily for 14 days

1- Bismuth subsalicylate (524 mg)
2- Tetracycline (500 mg)
3- Metronidazole (250 mg)
Because of the need for four-times daily dosing and the high side
effect profile, this regimen is no longer used as first-line therapy for H
pylori eradication.
New triple therapy: twice daily for 10–14 days
1- A proton pump inhibitor
2- Clarithromycin (500 mg)
3- Amoxicillin (1 g)
For patients who are allergic to penicillin, metronidazole (500 mg)
twice daily should be substituted for amoxicillin.

pharmacology
After completion of triple therapy, the proton pump inhibitor should
be continued once daily for a total of 4–6 weeks to ensure complete
ulcer healing.
IV-Vomiting
A-Emetics
They are agents that induced reflex vomiting.
They are used in emptying the stomach in awake patients who have ingested
a toxic substance or have recently taken a drug overdose.
Emesis should not be induced if the patient has central nervous system
depression or has ingested certain volatile hydrocarbons and caustic
substances.
1-Ipecac syrup (alkaloid emetine is the active principal ingredient)
 Action: It acts directly on the CTZ and also indirectly by irritating
the gastric mucosa.
 Adverse effects: Ipecac is cardiotoxic if absorbed and can cause
cardiac conduction disturbances, atrial fibrillation, or fatal
myocarditis. If emesis does not occur, gastric lavage using a
nasogastric tube must be performed.
2-Apomorphine (a derivative of morphine)
 Action: acts directly on the CTZ. It also is more effective if water is
first administered before oral or subcutaneous dosing.
 Adverse effects: Excessive dosage may cause respiratory depression
and circulatory collapse. Opioid antagonists such as naloxone usually
reverse the depressant actions of apomorphine.

pharmacology
B-Antiemetic drugs:
Antiemetics may prevent emesis by blocking the CTZ or by preventing
peripheral or cortical stimulation of the emetic center.
1-H1 antagonists:
 Diphenhydramine
 Dimenhydrinate
 Meclizine
They block H1 receptors in emetic center and vestibular system. They have
also antimuscarinic action.
Clinical Uses:
Most effective in motion sickness and vertigo.
Adverse effects:
Sedation and atropine like side effects e.g. dry mouth, blurred vision, and
urinary retention.
2-Anticholinergics:
 Hyoscine (scopolamine)
They block muscarinic receptors in emetic center and vestibular system and
GIT.
Uses:
Motion sickness and vertigo.
Adverse effects:
Atropine like side effects e.g. dry mouth, blurred vision, and urinary
retention.

pharmacology
3-Serotonin 5-HT3 Antagonists:
 Ondansetron
 Granisetron
 Dolasetron.
Action:
They block 5-HT3 receptors in CTZ and GIT.
Uses:
Chemically induced vomiting e.g. postoperative and cancer chemotherapy.
Adverse effects:
Constipation, headache and flushing.
4-Dopamine receptor blockers:
a. Metoclopramide and domperidone
 Action: block D2 and 5-HT3 receptors in CTZ and GIT.
 Uses: chemically induced vomiting and vomiting of pregnancy
(metoclopramide).
 Adverse effects: hyperprolactinaemia and CNS side effects (see
later).
b. Phenothiazines (e.g. prochlorperazine, promethazine and
thiethylperazine) and Butyrophenones (e.g. droperidol)
 Action: block D2 receptors in CTZ and block peripheral
transmission to emetic center.
 Adverse effects: hyperprolactinaemia, sedation, extrapyramidal
side effects (e.g. parkinsonism) and hypotension may occur.
5-Cannabinoids: Dronabinol
 Action: block opiate receptors in CTZ and emetic center.
 Uses: chemically induced vomiting not controlled by other
antiemetics.
 Adverse effects: dry mouth, sedation, psychosis, visual
hallucination and addiction

pharmacology
6-Benzodiazepines: Lorazepam or diazepam

 Action: mild antiemetic action may be due to their anxiolytic
and sedative effects.
 Adverse effects: sedation.
7-Corticosteroids: Dexamethasone, methylprednisolone
 Action: may be due to blockade of PGs.
 Adverse effects: see later.
8-Vitamin B6:
 Action: may be due to regulation of GABA (inhibitory CNS
transmitter) /Glutamine (excitatory CNS transmitter) balance.
 Uses: vomiting of pregnancy (drug of choice).

pharmacology
V-Motility of gastro-intestinal tract (GIT)

A- Purgatives:
They are drugs given to evacuate the bowels.
Laxatives are agents that cause mild purgation.
Cathartics are agents that cause severe purgation.
They are drugs given to evacuate the bowels in the following cases:
 Constipation.
 Drug and food poisoning (Mg SO4).
 Before and after some antihelmentics (Mg SO4).
 Bowel preparation before:
- X-ray on GIT.
- GIT operations.
 To prevent straining in patients with hernia, piles or
cardiovascular disease.
1-Bulk-Forming Purgatives:
 Natural plant products:
- Bran,
- Psyllium,
- Methyl cellulose
 Synthetic fibers
- Polycarbophil
Action:
Indigestible, hydrophilic colloids that absorb water, forming a bulky,
emollient gel that distends the colon and promotes peristalsis
Adverse effects:
Increased bloating and flatus.

pharmacology
2-Osmotic Purgatives:
 Lactulose,
 Mg sulphate
 Na/Ka tartrate.
Action:
Soluble but non absorbable compounds that increase the osmotic pressure in
the intestinal lumen result in increased stool liquidity due to retention of
water.
Adverse effects:
 Lactulose
- Nausea,
- Vomiting,
- Diarrhea
- Flatulence.
 Mg sulphate
- Hypermagnesemia and Hyperphosphatemia in patient with
renal diseases
 Na salts
- retention of sodium & water
3-Stimulant (irritant) Purgatives (Cathartics):
 Castor oil,
 Diphenylmethane Derivatives
- Phenolphthalein
- Bisacodyl
 Anthraquinone derivatives
- Cascara,
- Aloe
- Senna
- Rhubarb

pharmacology
Action:
They act on the mucosa of the intestine to stimulate peristalsis either by
irritation or by exciting reflexes in the mesenteric plexuses. They also inhibit
water absorption.
According to the site of irritation, castor oil is small bowel irritant but
diphenolmethane and anthraquinone are large bowel irritants.
Adverse effects:
Severe diarrhea which may cause dehydration & electrolyte loss, abdominal
colic and abortion in pregnant female (uterine contraction).
Diphenylmethane derivatives may cause rare but severe allergic reactions.
Chronic use of anthraquinone derivatives leads to a brown pigmentation of
the colon known as “melanosis coli”.
4-Lubricant Purgatives (Stool softeners):
 Mineral oil (Liquid paraffin),
 Docusate
 Glycerin suppository.
Action:
These agents soften stool material, permitting water and lipids to penetrate.
Adverse effects:
Long-term use of liquid paraffin can impair absorption of fat-soluble
vitamins (A, D, E, K) and it can result in a severe lipid pneumonitis if
inhaled into the lungs.
5-Misuse of purgatives:
Chronic use of purgatives may cause laxative habit or dependence due to:
- Loss of spontaneous bowel movements.
- Loss of spontaneous rectal defecation reflex.

pharmacology
B-Drugs that increase gastrointestinal motility (Prokinetics)
They are drugs that can selectively stimulate gut motor function. They
increase contractile force and accelerate intraluminal transit.
Effects and Uses:
 Agents that increase lower esophageal sphincter pressures may be
useful for Gastroesophageal Reflux Disease (GERD)
 Agents that enhance gastric emptying may be helpful for gastroparesis
and postsurgical gastric emptying delay.
 Agents that enhance small intestine emptying may be beneficial for
postoperative ileus or chronic intestinal pseudo-obstruction.
1-Cholinomimetic agents :
 Bethanechol
 Neostigmine
Action:
- Bethanechol : direct agonist at muscarinic M3 receptors on muscle
cells and at myenteric plexus synapses.
- Neostigmine: acetylcholinesterase inhibitor.
Adverse effects:
Cholinergic side effects include excessive salivation, nausea, vomiting,
diarrhea, and bradycardia.
2-Cisapride and Tegaserod:
They are serotonin-4 (5-HT4) receptor agonist on enteric neurons, which
promotes release of acetylcholine from the myentric plexus.
Adverse Effects:
Due to prokinetic effects in the colon, abdominal cramps and diarrhea may
occur.
In addition, cisapride rarely lead to serious cardiac arrhythmias.

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3-Metoclopramide and Domperidone :
They are dopamine D2 receptor antagonists potentiate cholinergic smooth

muscle stimulation (D2 receptors in GIT) and potent antiemetic action (D2
receptors in the chemoreceptor trigger zone of the medulla).
They have also agonist activity at serotonin-4 (5-HT4) receptors.
Adverse Effects:
Elevated prolactin levels (hyperprolactinaemia) can cause galactorrhea,
gynecomastia, impotence, and menstrual disorders.
- Metoclopramide: The most common adverse effects involve the
central nervous system (restlessness, drowsiness, insomnia, anxiety)
and extrapyramidal effects (dystonias, akathisia, parkinsonian
features) due to central dopamine receptor blockade. For this reason,
long-term use should be avoided.
- Domperidone: is extremely well tolerated. Because it does not cross
the blood-brain barrier to a significant degree, neuropsychiatric and
extrapyramidal side effects are rare.
4-Macrolide antibiotics : Erythromycin
They directly stimulate motilin receptors on gastrointestinal smooth muscles.
Intravenous erythromycin is beneficial in some patients with gastroparesis;
however, tolerance rapidly develops.
Adverse Effects:
Tachyphylaxis

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C-Antidiarrhoeals:
Antidiarrhoeals agents may be used safely in patients with mild to moderate
acute diarrhea.
However, they should not be used in patients with bloody diarrhea, high
fever, or systemic toxicity because of the risk of worsening the underlying
condition.
They should be discontinued in patients whose diarrhea is worsening despite
therapy.
Antidiarrhoeals are also used to control chronic diarrhea caused by such
conditions as irritable bowel syndrome (IBS) or inflammatory bowel disease
(IBD).
1-Opioid Agonists:
Natural
Opium tincture containing morphine.
 Synthetic
- Diphenoxylate
- Loperamide.
Activation of opioid receptors in the enteric nerve plexus results in inhibition
of propulsive motor activity and enhancement of segmentation activity.
Adverse Effects:
Central nervous system effects (sedation, respiratory depression, physical
dependence) limit the usefulness of most opioids.
- Loperamide does not cross the blood-brain barrier and has no central
effects (therefore, it is the opioid antidiarrheal of first choice.
- Diphenoxylate at the doses usually employed, has a low incidence of
central opioid actions. Commercial preparations commonly contain
small amounts of atropine to discourage overdosage (by atropine side
effects).

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2-Adsorbents:
 Kaolin (naturally occurring hydrated magnesium aluminum silicate),
 Pectin (indigestible carbohydrate derived from apples),
 Medicinal charcoal
 Chalk.
Action:
They bind diverse substances, including bacteria, toxins and fluid, thereby
permitting them to be inactivated and eliminated and decrease stool liquidity
and number.
Adverse Effects:
The adsorbents are generally safe, but they may cause constipation and may
interfere with the absorption of some drugs from the GI tract (bind to them)
so; they should not be taken within 2 hours of other medications.
3-Colloidal Bismuth Compounds: Bismuth subsalicylate
It also binds intestinal toxins and may coat irritated mucosal surfaces. It
reduces stool frequency and liquidity due to salicylate inhibition of intestinal
prostaglandin and chloride secretion.
4-Bile Salt Binding Resins:
 Cholestyramine
 Colestipol
They bind bile salts and excrete them in stool.
Clinical Use:
Chronic diarrhea due to bile salt malabsorption.
Adverse Effects:
Bloating, flatulence, constipation, and fecal impaction. They may interfere
with the absorption of some drugs from the GI tract (bind to them) so; they
should not be taken within 2 hours of other medications.

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5-Astringents: Tannic acid (home remedy: black tea) or metal salts
They precipitate surface proteins and are thought to help seal the mucosal
epithelium. Although astringents induce constipation, a therapeutic effect in
diarrhea is doubtful.
6-Antibacterial drugs:
Use of these agents (e.g., cotrimoxazole) is only rational when bacteria are
the cause of diarrhea. This is rarely the case.
It should be kept in mind that antibiotics also damage the intestinal flora
which, in turn, can give rise to diarrhea.
7-Oral rehydration solution:

(g/L of boiled water: NaCl 3.5, glucose 20, NaHCO32.5, KCl 1.5)
Oral administration of glucose-containing salt solutions enables fluids to be
absorbed because toxins do not impair the cotransport of Na+ and glucose
(as well as of H2O) through the mucosal epithelium.
In this manner, although frequent discharge of stool is not prevented,
dehydration is successfully corrected.

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D-Antispasmodics:
They are drugs used for the relief of the painful biliary, ureteral or colonic
spasms.
1-Anticholinergic drugs:
 Atropine,
 Propantheline,
 Dicyclomine,
 Oxybutynin
 Hyoscine butyl bromide(N-Butylscopolamine).
These drugs inhibit muscarinic cholinergic receptors in the enteric plexus

and on smooth muscle.
Adverse effects:
Anticholinergic side effects including dry mouth, visual disturbances,
urinary retention, and constipation.
2-Other smooth muscle relaxants:
 Papaverine
 Mebeverine
 Nitrites.
Papaverine and mebeverine are more specific on the colon

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VI- Drugs affecting biliary system

A-Antispasmodics:
They are used in cases of biliary colic.
B-Drugs for dissolving gallstones:
Bile acids:
 Chenodeoxycholic acid (CDCA)
 Ursodeoxycholic acid (UDCA).
They decrease the cholesterol content of bile. Thus, cholesterol-containing
stones can be dissolved with long-term oral administration.
UCDA is more effective and better tolerated than is CDCA.
C-Cholekinetics (Cholagogues)
Drugs that stimulate the gallbladder to contract and empty, e.g., egg yolk,
the osmotic laxative MgSO4, and cholecystokinin.
Cholekinetics are employed to test gallbladder function for diagnostic
purposes.

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VII-Other Gastrointestinal Drugs

A-Choleretics:
 Bile acids
 Bile salts
They are supposed to stimulate production and secretion of bile fluid. This
principle has little therapeutic significance.
B-Antiflatulents (Carminatives):
They serve to alleviate meteorism (excessive accumulation of gas in the
gastrointestinal tract).
Defoaming agents, such as dimethicone (dimethylpolysiloxane) and
simethicone, in combination with charcoal, are given orally to promote
separation of gaseous and semisolid contents.
C-Pancreatic enzymes:
From slaughtered animals are used to relieve excretory insufficiency of the
pancreas
( disrupted digestion of fats; steatorrhea).

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Unit V- Chemotherapy of Parasitic

Infections

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I- Anti-protozoal drugs
A-Treatment of Malaria
The malarial parasite is a single-cell protozoan (plasmodium).
Although more than 100 species of plasmodia have been identified, only
four are capable of infecting humans (Plasmodium malariae, P. ovale, P.
vivax, andP. falciparum)
 Drugs classification based on parasite cycle
A. Drugs that kill the parasite in the Pre-erythrocytic stage:
 Used for chemoprophylaxis.
c. Kill the parasite in the liver (Tissue schizonticide):
1. Primaquine. 2. Proguanil
d. Kill the parasite as soon as they reach RBCs:
1. Chloroquine. 2. Proguanil. 3. Fansidar.
B. Drugs that kill the parasite in the Erythrocytic stage (Blood
schizonticide)
 Used for clinical cure (treatment).
1. Chloroquine.
2. Quinine.
3. Mefloquine.
4. Pyrimethamine.
5. Sulfonamide combinations: e.g.
- Fansidar (Sulphadoxine + Pyrimethamine).
C. Drugs that kill the Gametocytes (Gametocide):
 Used for prevention of transmission.
1. Primaquine. 2. Proguanil. 3. Pyrimethamine.

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 Drugs used in malaria

1. Chloroquine
 Mechanism of action: inhibits DNA and RNA synthesis and
inhibits digestion of Hb by the parasite.
d. Antimalaria: see the table below.
e. Treatment of amebic liver abscess and giardiasis.
f. Treatment of rheumatoid arthritis and SLE.
d. Visual disturbances.
e. Hypotension and arrhythmia with i.v. injection.
f. Bone marrow depression.
2. Primaquine
 Mechanism of action: produce oxidizing metabolites that
interrupt mitochondrial functions of the parasite.
c. Sever hemolytic anemia: in patients with G6P defidiency.
d. Bone marrow depression.
3. Quinine
 Mechanism of action: inhibit DNA and protein synthesis.
e. Cinchonism: ringing in ears, blurred vision, sweating,
nausea.
f. Syncope and arrhythmia.
g. Blackwater fever: massive hemolysis with fever, dark urine
and renal failure.
h. Neurotoxicity.
4. Mefloquine
 Therapeutic uses: Antimalaria
 Adverse effects: neurotoxicity: headache, vertigo, psychosis.

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5. Antifolate drugs: Pyrimethamine, Proguanil, Fansidar
 Mechanism of action: inhibit folic acid synthesis→ inhibit
DNA synthesis.
 Therapeutic uses: Antimalaria;
Plasmodial strain Drug of choice
P. malariae and chloroquine-sensetive P. falciparum
 Prophylaxis and treatment (cure) Chloroquine
P. vivax, P. ovale
 Prophylaxis Chloroquine
 Treatment (cure) Chloroquine + Primaquine
(To prevent relapses i.e. radical cure).
Chloroquine-resistant P. falciparum
 Prophylaxis Chloroquine +
proguanil or fansidar or doxycycline
 Treatment (cure) 2. Quinidine +

fansidar or a tetracycline
Or 2. Mefloquine alone.

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B-Treatment of Amoebiasis
Amoebiasisis caused by the protozoan Entamoeba histolytica.
Classification of drugs
A. Luminal amoebicides:
 They are active only against the cysts present in the lumen of
intestine.
4. Diloxanide.
5. Iodoquinol
6. Antibiotics:
c. Erythromycin and paromomycin: are directly amebicidal.
d. Tetracyclines: act indirectly by inhibiting the bactrial
flora on which E.histolytica depend for its nutrition.
B. Systemic (Tissue) amoebicides:
 They
are active only against the invasive trophozoites in
tissues (intestinal wall, liver, and lung) but are ineffective
against the cysts in the intestinal lumen
3. Emetine and dehydroemetine.
4. Chloroquine (active against liver amoebiasis only).
C. Mixed amoebicides:
 They are active against both intestinal and tissue forms.
 Nitroimidazoles: e.g. metronidazole, tinidazole.
 Drugs used in amoebiasis
1. Diloxanide furoate
 Adverse effects: nausea, diarrhea, abdominal discomfort.
2. Iodoquinol
c. Antiamoebic; see the table below.
d. Balantidiasis (Balantidium coli) and giardiasis(Giardia
lamblia).
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d. Diarrhea, abdominal discomfort.
e. Thyroid enlargement.
f. eurotoxicity (optic atrophy, peripheral neuropathy).
3. Emetine and dehydroemetine

 Mechanism of action: block protein synthesis.
c. Direct myocardial depression, syncope.
d. Nausea, vomiting, and abdominal discomfort.
4. Chloroquine:
5. Metronidazole
 Mechanism of action: Inhibits DNA replication
e. Antiamoebic; see the table below.
f. Balantidiasis, giardiasis, and trichomoniasis (Trichomonas
vaginalis).
g. Dracunculiasis (Dracunculus medinensis) (medina worm)
(guinea worm)
h. Anaerobic infections: e.g. cancrum oris, peritonitis,
puerperal sepsis, etc.
e. GIT: nausea, vomiting, metallic taste, and hepatotoxicity.
f. CNS: vertigo, dizziness, convulsions
g. Mutagenicity and carcinogenicity (with prolonged use).
h. Dark brown urine.
 N.B. other nitroimidazoles have similar effects as
mitronidazole with longer duration of action.

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Amebiasis Drug of choice Comments
1st 2nd
Asymptomatic and Diloxanide furoate Iodoquinol

mild intestinal
infection
Moderate to severe Metronidazole + Paromomycin + Iodoquinol can be substituted

intestinal infection for diloxanide furoate.
(amebic dysentery) diloxanide furoate diloxanide furoate
Systemic amebiasis Metronidazole + Chloroquine + Although effective, emetine

and dehydroemetine are not
diloxanide furoate diloxanide furoate recommended because of
potential toxicity.
C-Treatment of Trichomoniasis and Giardiasis

Trichomoniasis:
It is caused by the protozoan Trichomonas vaginalis.

 Drugs of choice for treatment: Metronidazole, Tinidazole
 Relapses occur if the infected person’s sexual partner is not treated
simultaneously
.Giardiasis:
 It is caused by the protozoan Giardia lamblia.

 Drugs of choice for treatment: as trichomoniasis.

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 Treatment of Trypanosomiasis
1. Nifurtimox
 Mechanism of action: generation of toxic oxygen radicals.
 Therapeutic uses: south american trypanosomiasis (Chagas' disease).
 Adverse effects: nausea, vomiting, abdominal pain, skin rashes,
headache.
2. Suramin
 Adverse effects: acute reaction in sensitive individuals results in
nausea, vomiting, colic, hypotension, urticaria, and even
unconsciousness
3. Pentamidine isethionate
 Mechanism of action: inhibit DNA replication and function.
c. African trypanosomiasis (sleeping sickness).
d. Visceral leishmaniasis (kala azar) as an alternative to antimonials.
 Adverse effects: tachycardia, vomiting, shortness of breath, headache,
a fall in blood pressure, and changes in blood sugar (hypoglycemia or
hyperglycemia).
4. Eflornithine
 Mechanism of action: inhibits cell division, differentiation.
 Adverse effects: anemia and leukopenia.
5. Arsenicals: e.g. Melarsoprol
 Mechanism of action: affecting cellular structure and function.
 Therapeutic uses: african trypanosomiasis (sleeping sickness)
 Adverse effects: vomiting, abdominal cramps, fever, rashes, peripheral
neuropathy, most frequently adverse effect is encephalopathy.


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Trypanosomiasis Drug of choice
1st 2nd
Trypanosoma cruzi; it causes:
South American
trypanosomiasis
Nifurtimox
(Chagas' disease)
T. brucei; it causes:
African trypanosomiasis
(sleeping sickness)
a. Early stage Suramin (i.v.) + Pentamidine isethionate (i.m.)
(no CNS involvement) or
Eflornithine
b. Late stage Melarsoprol (Arsenicals) Eflornithine
(CNS involvement) or
Suramin followed by melarsoprol
D-Treatment of Leishmaniasis
Antimonials: e.g. Stibogluconate
 Therapeutic uses: leishmaniasis
 Adverse effects: coughing, myalgia, arthralgia, rashes, abdominal pain,
diarrhea, and anaphylactoid collapse, and pancreatitis.

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Leishmaniasis Drug of choice
1st 2nd
Leishmania braziliensis and L. mexicana ; they cause:
American mucocutaneous leishmaniasis Stibogluconate Amphotericin B

(antimonials)
L. donovani ; it causes:
Visceral leishmaniasis Stibogluconate Pentamidine

(antimonials) isethionate
(kala azar)
L. tropica & L. major ; they cause:
Cutaneous leishmaniasis (oriental sore) Stibogluconate

(antimonials)

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II-Anti-helmintic drugs
 Different helminth (metazoan) infection
Nematode (Round worm) Infections Cestode (Tape worm) Trematode (Flukes) Infections
(Flat worm) Infecti ons
A. Intestinal nematodes 2. Taenia saginata (Beef A. Bl ood Fluke Infecti ons
1. Ascaris lumbricoides tapeworm) (Schistosomi asis)
2. Ancylstoma duodenale (Hookworm) 2. Taenia solium (Pork tapeworm) a. Schistosoma hematobium
3. Enterobius vermicularis (Oxyuris) 3. Diphyllobothrium latum (Fish b. Schistosoma mansoni
(Pinworm) tapeworm) c. Schistosoma japonicum
4. Trichuris trichiura (Whipworm) 4. Hymenolepis nana (Dwarf
5. Strongyloides stercoralis tapeworm) B. Intestinal Fluke Infecti ons
5. Echinococcus granulosus and d. Heterophyes heterophyes
B. Tissue nematodes Echinococcus multilocularis
1. Filaria worms (Wuchereria bancrofti, (Hydatid disease) e. Fasciolopsis buski
Brugia malayi, Loa loa ) f. Metagonimus yokogawai
2. Dracunculus medinensis (Medina worm)
(Guinea worm) C. Li ver Fluke Infections
3. Larva migrans d. Fasciola hepatica
 Cutaneous larva migrans
 Visceral larva migrans e. Opisthorchis felineus
f. Clonorchis sinensis
D. Lung Fluke Infecti ons

a. Paragonimus westermani
b. Paragonimus kellicotti
 Drugs used for their treatment

A. Drugs used for treatment of nematodes:
1. Mebendazole
 Mechanism of action: inhibits glucose uptake and causes paralysis of
the parasite through inhibition of microtubules system
 Therabutic uses:
1. Intestinal nematodes.
2. Visceral larva migrans.
3. Hydatid disease.
4. Taenia saginatum and solium.

pharmacology
 Adverse effects: mild and infrequent because less than 10% is
absorbed.
2. Thiabendazole
 Mecanism of action: as mebendazole.
1. Treatment of strongloides and medina worm (drug of choice).
2. Cutaneous and visceral larva migrans (because it is well
absorbed).
 Adverse effects: mild GIT upset and neuropsychatric symptoms.
3. Levamisole
depolarizing neuromuscular blocking action. It has
immunopotentiating effect on T cell function in man.
1. Treatment of ascaris and ankylostoma.
2. As immunopotentiator in some diseases e.g. colon cancer.
 Adverse effects: mild GIT upset and skin rash.
4. Pyrantel pamoate
depolarizing neuromuscular blocking action.
1. Treatment of enterobius.
2. Treatment of ascaris, ankylostoma and mixed infection of both.
 Adverse effects: it is a safe drug.
5. Diethylcarbamazine
 Mechanism of action: it causes paralysis of microfilaria and alters
their surface structure, making them more susceptible to destruction
by host defense mechanisms.
 Therapeutic uses: treatment of filarial.
 Adverse effects: sudden death of the microfilaria can produce severs
allergic reactions e.g. fever, lymphadenopathy, leukocytosis,
esinophilia, edema , rashes.

pharmacology
B. Drugs used for treatment of trematodes

1. Praziquantel
 Mechanism of action: spastic paralysis of the parasite.
1. Treatment of schistosomiasis: active against all species.
2. Treatment of other flukes: intestinal, liver, and lung flukes.
N.B. not effective in treatment of Fasciola hepatica.
3. Cestodes: T. saginata, T.solium, D.latum, H.nana
 Adverse effects: nausea, vomiting, drowsiness, arthralgia and
myalgia.
2. Other anti-bilharzial drugs

a. Metrifonate: it is active only against Schistosoma hematobium.
b. Oxaminiquine: it is active only against Schistosoma mansoni.
3. Drugs active against Fasciola hepatica

c. Bithionol: drug of choice.
d. Dihydroemetine: alternative to bithionol.
C. Drugs used for treatment of cestodes
1. Niclosamide
 Therapeutic uses: alternative to praziquantel in treatment of T.
saginata, T.solium, D.latum, H.nana
 Adverse effects: very minimal (not absorbed from GIT).
2. Quinacrine
It is an alternative drug in the treatment of T.solium.

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Unit VI-Chemotherapy of Microbial

diseases

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pharmacology
I- Antimicrobial agents:
They are any chemical substances that can kill or inhibit the growth of
microorganisms.
Antibiotics:
They are natural chemical substances obtained from living organisms which
can kill or inhibit the growth of microorganisms.
Chemotherapeutics:
They are synthetic chemical substances which can kill or inhibit the growth
of microorganisms.
Bactericidal agents:
kill infecting organism e.g. penicillin.
Bacteriostatic agents: slow growth of infecting organism (i.e. depends
greatly on active host defense mechanisms) e.g. sulphonamides.

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A-Mechanism of action of antimicrobial agents
1-Inhibition cell wall synthesis by:
 Inhibition of peptidoglycan cross-linking (β-lactam antibiotics)

- Penicillins,
- Cephalosporins,
- Monobactams,
- Carbapenems.
 Block peptidoglycan synthesis
- Bacitracin,
- Vancomycin
2-Inhibit protein synthesis by:

- Macrolides, chloramphenicol, lincomycin, clindamycin,
streptogramins (quinupristin, dalfopristin)
- Aminoglycosides,
- Tetracyclines
3- Inhibit folic acid pathway:

- Sulfonamides,
- Trimethoprim
4-Inhibit DNA synthesis :

- Quinolones,
- Flucytosine.
5-Inhibit mRNA synthesis:

- Rifampin
6-Disrupt cell membranes:

- Azoles,
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- Polymyxins,
- Amphotericin B,
- Nystatin.
7. Unknown
- Pentamidine
B-Resistance to antimicrobial agents
1-Biochemical mechanisms:
 Production of inactivating enzymes

- β-lactamases → inactivate β-lactam antibiotics (penicillin,
cephalosporins, monobactam).
- Acetylase → inactivate aminoglycosides.
- Transacetylase → inactivate chlorq,phenicol
 Reduced bacterial permeability to antibiotics (tetracyclines).
 Alteration of the receptor sits on the ribosome e.g. erythromycin,
aminoglycosides.
 Development of altered metabolic pathway that bypass the reaction
inhibited by the drugs e.g. sulphonamides.
2-Genetic basis of resistance:

 Chromosomal resistance: due to spontaneous mutation of the gene
responsible for suscepetability of microorganism to antimicrobial.
 Extra-chromosomal resistance: due to transfer of genetic material
from resistant bacteria to another.
Cross resistance:
Microorganisms resistant to a certain drug may also be resistant to drugs that
share the same mechanism of action (e.g. neomycin & kanamycin) or
chemical structure (e.g. β-lactam antibiotics).

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Prevention of antimicrobial resistance:
1. Prevent the misuse of antimicrobial agents: see later.
3. Use drug combination in resistant strains e.g. in T.B.
C-Selection of an antimicrobial agent
Selection from among several drugs depends upon:

1-Antimicrobial spectrums:
The susceptibility of the organism to a specific agent.
2-Host factors
 Host factors include the following:
 Prior hypersensitivity and other adverse drug effects.
 Concomitant disease states e.g. bactericidal drugs are preferred in
immunocompromised patients.
 Impaired elimination or detoxification of the drug (this may be
genetically predetermined but more frequently is associated with
impaired renal or hepatic function due to underlying disease)
 Age of the patient
 Pregnancy status.
3-Pharmacologic factors:
 The kinetics of absorption, distribution, metabolism, and elimination
(pharmacokinetic).
 The ability of the drug to be delivered to the site of infection (which
depends on the pharmacokinetics and the available dosage forms of
the drug).
 The potential toxicity of an agent.
 Pharmacokinetic or pharmacodynamic interactions with other drugs.
4-Other factors:
The cost of antimicrobial therapy, especially when multiple agents with
comparable efficacy and toxicity are available for a specific infection.

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D-Reasons for antimicrobial combination therapy
Most infections should be treated with a single antimicrobial agent.
Although indications for combination therapy exist in several cases:
 To provide broad-spectrum empirical therapy in emergent serious

infections such as septicemia (no time for bacteriological diagnosis).
 To treat mixed (polymicrobial) infections such as intra-abdominal
abscesses.
 To prevent or delay the development of resistant strains e.g.
antimicrobial combination for tuberculosis.
 To decrease dose-related toxicity by using reduced doses of one or
more components of the drug regimen e.g. flucytosine in combination
with amphotericin B for the treatment of cryptococcal meningitis
allows for a reduction in amphotericin B dosage with decreased
amphotericin B-induced nephrotoxicity.
 To obtain enhanced inhibition or killing (Synergism) e.g.
sulfamethoxazole + trimethoprim to form co-trimoxazole.
E-Misuses of antimicrobials
Antimicrobials are often misused in clinical practice.
The unnecessary use of antimicrobials may lead to:

 Increase toxicity.
 Superinfections (opportunistic infection): due to inhibition of bacterial
flora by the prolonged oral administration of broad spectrum
antibiotics  multiplying (superinfection) of the bacteria and fungi
that are normally inhibited by bacterial flora  diarrhea or
pseudomembranous colitis.
 Reduced efficacy of the antimicrobial agents: due to antagonism of
one drug by another or development of microbial resistance.
 Increase costs.

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To avoid that; the antimicrobials should be used only when necessary and
with the following cautions:
 Proper selection
 Proper dose.
 Sufficient duration of therapy (at least for 3 days after clinical cure).
 Restrict use of valuable drug in treatment of minor infections e.g. the
use of rifampine in treatment of tonsillitis.
 Restrict use of antimicrobial combinations unless indicated.

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II-Agents used for treatment of bacterial infections

A-Sulphonamides:
1-Chemistry:
Synthetic analogues of P-aminobenzoic acid (PABA).
They inhibit bacterial folic acid pathway ;bacteriostatic.
3-Classification:
 Oral absorbable: well absorbed from GIT, cross BBB.
- Short acting: e.g. sulfadiazine
- Long acting: e.g. sulfadoxine
 Oral poorly absorbable: e.g. sulfathalidine
 Topical:
- Sulfathiazole for wounds in absence of pus.
- Sulfamafenide for wounds and burn in presence of pus.
- Sulfacetamid eye drops for eye infections.
4-Spectrum:
 Gram +ve and Gram-ve (but narrow spectrum).
 Chlamydia, toxoplasma, and plasmodium falciparum.
5-Therapeutic uses:
 To treat infections caused by susceptible organisms, like:

 Meningococcal meningitis (sulfadiazine).
 Prophylaxis against streptococcal infection (e.g. tonsillitis) in patients
with rheumatic fever who are hypersensitive to penicillin
(sulfadiazine).
 Bacillary dysentery (sulfathalidine).
 Acute uncomplicated urinary tract infection.
 Chlamydia infection e.g. trachoma (sulfacetamide eye drops).
 Preventing infection of wounds and burn (sulfamafenide)

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6-Adverse effects:
 Hypersensitivity reactions,
 Crystalluria,
 Anemia,
 Hemolysis if G6PD deficient,
 Nephrotoxicity,
 kernicterus in infants.
7-Sulfonamide combinations:
 Co-trimoxasole (sulfamethoxazole + trimethoprim)
 Mechanism of action: inhibit two successive steps in the
enzymatic pathway of folinic acid synthesis; bactericidal.
PABA  Folic acid  Folinic acid
- -
Sulphonamides Trimethoprim
1. Respiratory tract infection due to H. influenza.
2. Complicated urinary tract infection.
3. Typhoid fever and Shigellosis.
4. Gonococcal urethritis.
Adverse effects: like sulfonamides plus: hypersensitivity
reactions, megaloplastic anemia, and teratogenicity.
 Precautions: contraindicated pregnancy due to teratogenicity.
 Other sulfonamides combinations:
a. Sulfadoxine + Pyrimethamine (Fansidar): for treatment of
malaria caused by chloroquine-resistant Plasmodium
falciparum.
b. Sulfadiazine + Pyrimethamine: for treatment of
toxoplasmosis.
c. Silver sulfadiazine: applied locally to prevent infections of
wounds and burn.

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B-Quinolones:
1-Chemistry:
Synthetic analogues of nalidixic acid.
Inhibit DNA synthesis; bactericidal.

3-Classification and spectrum:
 1st generation: narrow spectrum (G -ve)
- e.g. nalidixic acid
 2nd generation: broad spectrum (G -ve and some G +ve)

- e.g. pipemidic acid
 3rd generation (fluoroquinolones): broader spectrum (G -ve, G +ve,
and pseudomonas)
- e.g. ciprofloxacin, norfloxacin, ofloxacin
 4th generation: extended spectrum (G -ve, G +ve, pseudomonas, and
anaerobs).
- e.g. trovafloxacin
4-Therapeutic uses:
 Urinary tract infections and prostatitis.
 Meningitis.
 Respiratory tract infections.
 Typhoid fever.
 Skin infections and osteomyelitis.
 Severe systemic infections: 3rd and 4th generations.
5-Adverse effects:
 GI upset (nausea, vomiting, abdominal pain),
 Skin rashes,
 Neurological side effects (headache, dizziness, visual disturbance),
 Tendonitis and tendon rupture in adults.

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Precautions: contraindicated in pregnancy and in children because animal

studies show damage to cartilage.
C-Penicillins
1-Chemistry:
6-aminopenicillanic acid (contain β-lactam ring).
Inhibit bacterial cell wall synthesis; bactericidal.
3-Classification:
 Benzyl penicillin and related drugs:
- Injectional preparations:
- Benzyl penicillin (penicillin G): short acting (given every 6
hours).
- Procaine penicillin: long acting (given every 12 hours).
- Fortified procaine penicillin: longer acting (given every 24
hours).
- Benzathine penicillin: longest acting (given every 3-4
weeks).
- Oral preparations:
- phenoxymethyl penicillin (penicillin V) and phenethicillin.
 Broad spectrum penicillins:
1. Ampicillin
2. Pro-drugs of ampicillin: pivampicillin and talampicillin.
- activated only after absorption and they have better absorption
and distribution than ampicillin.
3. Amoxycillin: better absorption and distribution than ampicillin.

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N.B. Clavulanic acid and sulbactam are β-lactamase inhibitors
combined with amoxicillin and ampicillin to include β-lactamase
producing organisms.
 Antipseudomonal penicillins: mainly used for treatment of
Pseudomonas aeruginosa infection and other G –ve rods.
1. Carbenicillin group: e.g. carbenicillin, ticarcillin.
2. Ureidopenicillin group: e.g. azlocillin, pipracillin.
 Amidinopenicillins:
1. Mecillinam: highly active against G –ve bacteria.
2. Pivmecillinam: it is prodrug of mecillinam.

 Penicillinase resistant penicillins (Antistaph penicillins): mainly
used for treatment of Staphylococcus aureus infection.
1. Methicillin
2. Cloxacillin and flucloxacillin
3. Nafcillin
4-Spectrum:
- G +ve and most G –ve bacteria
(Benzyl penicillin and related drugs not effective against G –ve
bacilli)
- Spirochetes: Tyrponoma pallidum.
- Actinomyces.
All penicillins are β-lactamase susceptible, except penicillinse
resistant penicillins (antistaph penicillins).
5-Therapeutic uses:
Infections caused by susceptible organisms. For example:
 Treatment of:
- Streptococcal infections e.g. throat infections.
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- Staphylococcal infections e.g. pyrogenia infections.
- Pneumococcal infections e.g. pneumonia.
- Meningococcal meningitis.
- Syphilis and gonorrhoea.
- Typhoid and paratyphoid fevers: ampicillin and amoxicillin.
- Pseudomonas infection: antipseudomonal penicillins.
- Actinomycosis and anthrax.
- Diphetheria, tetanus, and gas gangrene (together with
antitoxins).
 Prophylaxis:
- Prevent recurrence of acute rheumatic fever: benzathine
penicillin.
- Prevent gonorrheal ophthalmia in neonates: benzyl penicillin
eye drops.
- Prevent subacute bacterial endocarditis before dental extraction.
6-Adverse effects:
 Hypersensitivity reactions (10% of patients),
 GIT upset (anorexia, nausea, vomiting, diarrhea)
D-Cephalosporins:
1-Chemistry:
7-aminocephalosporanic acid (contain β-lactam ring).
2-Mechanism of action: as penicillins.
3-Classification and Spectrum:
 1st generation:
- e.g. cephadroxil, cephradine, cephalexin
- spectrum: more on G +ve.
 2nd generation:
- e.g. cefaclor, cefuroxime, cefoxitin
- spectrum: G –ve and G +ve.
 3rd generation:
- e.g. cefixime, cefotaxime, cefoperazone, ceftriaxone

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- spectrum: more on G –ve and pseudomonas.
 4th generation:
- e.g. cefepime
- spectrum: G –ve, G +ve, pseudomonas, and anaerobes.
4-Therapeutic uses:
 Bacterial meningitis.
 Skin, bone, joint infections.
 Urinary tract infection.
 Pelvis, abdomen, and chest infections caused by mixed organisms.
 Bacteraemia of unknown organism.
 Pseudomonal infection.
 Penicillin resistant streptococcal infection.
 Penicillin resistant gonococci.
5-Adverse effects:
 Hypersensitivity reactions
 Nephrotoxicity.
E-Aminoglycosides:
 Streptomycin
 Gentamicin
 Neomycin
 Kanamycin
 Amikacin
 Tobramycin
1-Chemistry:
Amine-containing carbohydrate.
They are either natural products or derivatives of soil actinomycetes.
subunit; bactericidal.

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3-Spectrum:
Mainly on G –ve and few G +ve (narrow spectrum).
4-Therapeutic uses:
 Streptomycin and kanamycin:

dysentery.
- Treatment of TB
 Neomycin:
dysentery.
- Orally in hepatic coma to kill flora of the gut (to decrease
production of ammonia)
 Gentamicin, tobramycin, amikacin:
- Treatment of pneumonia, urinary tract infections, and
osteomylitis.
- Treatment of peritonitis (with penicillin and metronidazole).
- Pseudomonas infections (with carbenicillin).
- Topically for skin and eye infections.
5-Adverse effects:
 Ototoxicity (especially when used with loop diuretics),
 Nephrotoxicity (especially when used with cephalosporins),
 Neuromuscular block.

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F-Tetracycline:
 Tetracycline
 Doxycycline
 Demeclocycline
 Minocycline
1-Chemistry:
They have different chemical structures and are produced by different
species of Streptomyces.
subunit; bacteriostatic.
3-Spectrum:
 Most G +ve, G –ve, and some anaerobes.
 Rickettsia, coxiella, mycoplasma and Chlamydia, and brucella.
 Spirochetes, actinomyces, protozoa.
4-Therapeutic uses:
 Treatment and prophylaxis of Cholera.
 Mixed bacterial infection of respiratory tract e.g. sinusitis, bronchitis.
 Second choice after penicillins in Syphilis, Gonorrhea, Actinomycosis,
Anthrax, and Shigellosis.
 Diseases caused by Rickettsia (typhus) and Coxiella.
 Chlamydial disease e.g trachoma.
 Treatment of Brucellosis and Plague.
 Treatment of Mycoplasma pneumoniae.
 Treatment of acne vulgaris (doxycycline and minocycline).
 Bacillary and Ameoebic dysentery.
 Treatment of chloroquin resistant P. falciparum (with quinidine).
 Local for eye and skin infections.

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5-Adverse effects:
 GIT distress
 Discolor of teeth
 Inhibition of bone growth in children,
 Hepatotoxicity,
 Nephrotoxicity,
 Teratogenicity.
Precautions:
Contraindicated in pregnancy, lactation, children (less than 8 years of age).

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G-Macrolides:
 Erythromycin
 Azithromycin
 Clarithromycin
1-Chemistry:
They consist of a large lactone ring to which sugars are attached.
subunit; bacteriostatic in low concentration and bactericidal in high
concentration.
3-Spectrum:
 Mainly G +ve bacteria
 Mycoplasma and Chlamydia.
4-Therapeutic uses:
 Treatment of Staphylococcal, Streptococcal, Pneumococcal,
H.influenza, Gonorrhea and Syphilis infections in penicillin-sensitive
patients.
 Eradication of Corynbactrium diphtheriae from pharyngeal carriers.
 Treatment of Mycoplasma pneumonia infections in infants.
 Treatment of Chlamydial infections in pregnancy and infants.
 Treatment of Toxoplasma infection (clarithromycin).
5-Adverse effects:
 GIT discomfort (most common cause of noncompliance)
 Acute cholestatic hepatitis
 Eosinophilia
 Skin rashes.

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H-Antiseptics and disinfectants
Disinfection refers to the inactivation or killing of pathogens (protozoa,
bacteria, fungi, viruses) in the human environment.
Sterilization refers to the killing of all microorganisms, whether pathogenic,
dormant, or nonpathogenic.
Antisepsis refers to the reduction by chemical agents of numbers of
microorganisms on skin and mucosal surface.
Properties of an ideal disinfectant:
 Broad spectrum of activity.
 High potency under conditions of use.
 Ready solubility or miscibility with water.
 Non caustic with a low degree of toxicity and without harmful or
sensitizing effects on delicate tissues.
 Complete compatibility with other antimicrobial agents.
 Stable on storage and over a wide pH range.
 Economical, no offensive odor, non-staining.
1-Phenols:
 Crude phenols or its derivatives (dettols, lysols, cresols).
Not inactivated by organic matter but they are toxic and irritant.
2-Alcohols:
- 70 % ethanol & 50 - 70 % isopropyl alcohol.
They should not be diluted to be effective.
3-Oxidizing agents:
 Hydrogen peroxide for infected wounds.
 Potassium permanganate for superficial fungal infection.
 Halogens: e.g.:
o Chlorine: disinfection of water.
o Hypochlorite compounds for fomites and clothes .
o Iodine tincture is the best skin disinfectant.

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4-Cationic surface active agents: (detergents and soaps).
 Cetavlon,
 Zephiran
 Cetrimide.
Non toxic, non irritant compounds.
Bound to and inactivated by plant fibers (cotton & gauze).
5-Salts of heavy metals:
 Mercurochrome for wound infections.
 Merthiolate for preservation of vaccines.

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I-Agents used for the treatment of Tuberculosis (TB)
 Tuberculosis (TB) is caused by TB bacilli (Mycobacterium
tuberculosis).
 Anti-tuberculus drugs must be highly lipid soluble to penetrate cell
membrane of the host and lipid coat of the TB bacilli (streptomycin is
exception).
I- 1st line drugs: II- 2nd line drugs:

1. Isoniazide (INH). 1. Capreomycin.
2. Rifampin. 2. Cycloserine.
3. Ethambutol. 3. Fluorinated quinolones.
4. Streptomycin. 4. Para amino salicylic acid (PAS).
5. Pyrazinamide. 5. Kanamycin.
I- 1st line drugs:
 Isonizid (INH)
 Mechanism of action: decreases synthesis of mycolic acids→↓ cell
wall synthesis.
2. Prophylaxis against TB in certain cases e.g. close contact to recent
diagnosed cases.
 Adverse effects: hemolysis if G6PD deficient, neurotoxicity
(peripheral neuropathy, optic neuritis), hepatotoxicity, SLE-like
syndrome.
 Rifampin
 Mechanism of action: Inhibits DNA-dependent RNA polymerase→↓
RNA synthesis.

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2. Treatment of leprosy.
3. Treatment of resistant staphylococcal infections and prostatitis.

4. Treatment of meningococcal carrier state.
5. Prophylaxis in contacts of children with H. influenzae type B.
6. Treatment of Pox virus (it interferes with envelope formation).
 Adverse effects: mild hepatotoxicity, drug interactions (↑ P450), and
red/orange body fluids (harmless).
 Ethambutol
 Mechanism of action: unknown (ma be due to ↓ RNA synthesis).
 Therapeutic uses: treatment of active TB.
 Adverse effects: visual disturbances (field defects, color blindness,
optic neuritis), peripheral neuritis, hyperuricemia.
 Pyrazinamide
 Used in combination with INH and rifampin to minimize resistance.
 Adverse effects: hepatotoxicity, hyperuricemia.
 Streptomycin
 Used in combination with INH and rifampin to treat military TB,
extensive pulmonary and renal TB.
 Adverse effects: see aminoglycosides.
II- 2nd line drugs:

 They are less effective and more toxic than 1st line drugs.
 For example; para amino salicylic acid (PAS) causes bone marrow
depression, gastric ulceration, thyroid injury, and neurological
symptoms.
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 They used only when resistance or severe side effects developed to 1 st
line drugs.
 Regimen of TB therapy:
1. Initial intensive course (2-4 months):
- At least 3 drugs are used (INH + Rifampin + Pyrazinamide).
- A 4th drug may be added if resistance is possible (Etambutol or
Streptomycin).
2. Continuation phase (4-12 months):
- (INH + Rifampin) and Ethambutol may be added if resistance is
suspected.
J-Agents used for the treatment of Leprosy
Leprosy is the disease caused by Mycobacterium leprae.
1-Dapson
Chemistry:
Structural analogue of PABA and chemically related to sulfonamides.
Mechanism of action: similar to sulfonamides.
Therapeutic uses:
Treatment of leprosy (given for 2-4 years with rifampin and/or clofazimne to
avoid development of resistance)
Adverse effects: similar to sulfonamides.
2-Clofazimine
Chemistry: phenazine dye.
Mechanism of action: inhibit mycobactria DNA synthesis; bactericidal.

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Therapeutic uses:
Treatment of leprosy (with rifampin and clofazimne to avoid development of
resistance)
Adverse effects: abdominal pain, atropine like effects, dark brown
discoloration of skin, cornea, and all body fluids.
3-Rifampin:
It is the most active antilepromatous drug available.

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III-Antifungal agents
Fungal infections (mycosis) are usually confined to the skin or mucous
membranes (local or superficial mycosis).
However, in immune deficiency states, internal organs may also be affected
(systemic or deep mycosis).
Agents used for superficial fungal infections
 Azoles.
 Polyenes antibiotics:
- Nystatin,
- Amphotricin-B.
 Grisofulvin
 Non related topical antifungal:
- Naftifine
- Ciclopiroxolamine
- Haloprogen.
 Old topical agents: Whitfield ointment, gentian violet, tincture iodine.
Agents used for systemic fungal infections
 Azoles.
 Amphotricin-B.
 Flucytosin
A-Azoles:
 Fluconazole,
 Ketoconazole,
 Clotrimazole,
 Miconazole,
 Itraconazole
They disrupt cell membrane permeability (by inhibiting ergosterol
synthesis).

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2-Therapeutic uses:
 Superficial fungal infection:
- Dermatophytes infection of skin (e.g. tinea), hair (e.g.
ringworm), and nail (e.g. paronychia).
- Mucocautaneous candidiasis: e.g. oropharyngeal and
vulvovaginal candidiasis.
 Systemic fungal infections: e.g. cryptococcal meningitis in AIDS
patients (fluconazole).
3-Adverse effects:
 Hepatotoxicity
 Microsomal enzyme inhibition,
 Antianderogenic effects (impotence and gynecomastia)
 Fluid retention.
B-Polyenes antibiotics:
 Nystatin
 Amphotricin-B
They disrupt cell membrane (by forming membrane pores that disrupt
homeostasis).
2-Therapeutic uses:
 Local uses (amphotricin-B and nystatin topically):
- Eye drops for fungal corneal ulcers.
- Lozenges for oral candidiasis.
- Tablets for intestinal candidiasis.
- Vaginal tablets for vaginal candidiasis.
 Systemic (amphotricin-B only by parenteral route):
- Systemic mycosis (i.v.).
- Intrathecally for fungal meningitis (can not cross blood brain
barrier).
- American leshmaniasis (i.v.).

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3-Adverse effects (iv. injection of amphotricin-B):
 Hepatotoxicity,
 Nephrotoxicity,
 Direct myocardial toxicity (arrhythmia, hypotension),
 Fever, chills, and headache.
C-Grisofulvin
It interferes with microtubule function, disrupts mitosis. Deposits in keratin-
containing tissues (e.g., nails).
2-Therapeutic uses:
It is given orally for:
 Superficial fungal infection: dermatophytes infection of skin (e.g.
tinea), hair (e.g. ringworm), and nail (e.g. paronychia).
N.B. it deposits in keratin-containing tissues (e.g. skin and nails).
3-Adverse effects:
 Hepatotoxicity
 Leukopenia
 Photosensitivity
 Nausea, vomiting
 Teratogenicity and carcinogenicity.
D-Flucytosin
It inhibits DNA synthesis.
2-Therapeutic uses:
 Systemic mycosis
 Fungal meningitis.

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3-Adverse effects:
 Hepatotoxicity,
 Bone marrow depression,
 Loss of hair
E-Non related topical antifungal:
 Naftifine: effective only against skin dermatophytes.
 Ciclopirox olamine: broad spectrum against dermatophytes and

yeasts.
F-Old topical agents:
 Whitfield ointment (salicylic acid + benzoic acid + vaseline): act as
keratolytic and fungicidal (to remove infected keratin).

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IV-Antiviral agents

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Steps of viral replication and main sites of action of antiviral drugs:

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A-Anti-herpes virus agents:
1-Acyclovir:
It preferentially inhibits viral DNA polymerase when phosphorylated by
viral thymidine kinase.
Therapeutic uses:
 treatment of Herpes simplex virus (HSV),
 varicella zoster virus (VZV).
 Prophylactic in immunocompromised patients.
Adverse effects:
 Neurotoxicity (delirium, tremor),
 Nephrotoxicity.
2-Ganciclovir
Mechanism of action: similar to acyclovir.
Therapeutic uses:
As acyclovir, but mostly used in treatment and prophylaxis of CMV
(especially in immunocompromised patients).
Adverse effects:
 Leukopenia
 Neutropenia
 Thrombocytopenia
 Nephrotoxicity
 More toxic to host enzymes than acyclovir.

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3-Foscarnet:
Viral DNA polymerase inhibitor that binds to the pyrophosphate binding site
of the enzyme (pyrofosphate analog). Does not require activation by viral
kinase.
Therapeutic uses:
As ganciclovir, with increased activity versus acyclovir-resistant strains of
HSV.
Adverse effects: nephrotoxicity.

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B-Anti-retroviral agents
1-Protease inhibitors:
 Saquinavir
 Ritonavir
 Indinavir
 Nelfinavir
They inhibit assembly of new virus by blocking protease enzyme.
Adverse effects:
 GI intolerance (nausea, diarrhea),
 Hyperglycemia
 Lipid abnormalities
 Thrombocytopenia (indinavir).
2-Reverse transcriptase inhibitors
 Nucleosides:
- Zidovudine (AZT),
- Didanosine (ddI), Zalcitabine (ddC),
- Stavudine (d4T),
- Lamivudine (3TC)
 Non-nucleosides:
- Nevirapine,
- Delavirdine
They preferentially inhibit reverse transcriptase of HIV; prevent
incorporation of viral genome into host DNA.
Adverse effects:
 Bone marrow suppression (neutropenia, anemia),
 Peripheral neuropathy,
 Lactic acidosis (nucleosides);
 Rash (non-nucleosides);

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 Megaloblastic anemia (AZT).
Therapeutic use of anti retroviral agents:
They are used in HIV infection (Human immunodeficiency virus) (AIDS).
 HIV Triple therapy: entails use of two nucleoside reverse
transcriptase inhibitors with a protease inhibitor, though other
combinations, such as the substitution of a non-nucleoside for a
protease inhibitor, are used. Initiated when patients have low CD4
counts (< 500 cells/mm3) or high viral load.
 AZT used during pregnancy to reduce risk of fetal transmission.

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C-Other antiviral agents
1-Gamma globulin (immune globulin)
 They are antibodies concentrated from plasma of persons with high
antibody levels or prepared by genetic engineering.
 Mechanism of action: attach to the envelope of susceptible virus and
block its penetration into the host cell (passive immunization).
 Therapeutic uses: non specific (all viral infections) but must be given
early by IV or IM injections.
 Adverse effects: hypersensitivity reactions.
2-Amantadine
 Mechanism of action: blocks viral penetration/uncoating. Also causes
the release of dopamine from intact nerve terminals.
 Therapeutic uses: prophylaxis for influenza A, Parkinson’s disease.
 Adverse effects: ataxia, dizziness, slurred speech.
3-Ribavirin
 Mechanism of action: inhibits synthesis of guanine nucleotides by
competitively inhibiting IMP dehydrogenase.
 Therapeutic uses: pneumonia and bronchiolitis of infancy caused by
respiratory syncytial virus (RSV).
 Adverse effects: hemolytic anemia, upper airway irritation
4-Interferons
 They are natural endogenous glycoproteins.
 Mechanism of action: interferon-α (from human leukocytes) blocks
various stages of viral RNA and DNA synthesis.
 Therapeutic uses: Chronic hepatitis C and B, Kaposi’s sarcoma.
 Adverse effects: neutropenia, flu-like symptoms (fatigue, depression,
muscle weakness), hepatic dysfunction.
5-Rifampin
 It inhibits assembly of poxvirus by preventing the envelope formation.
It is not used in treatment of human poxvirus infection but topical
application can inhibit human vaccinia lsions.

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V-Idea about vaccines and Toxoids

Vaccines:
They are weapons to prevent diseases. They may be made of
microorganisms similar to the ones that cause diseases, or of the toxins
produced by the microorganisms after changing them into harmless toxoids.
Types of vaccines:
 Live vaccines: containing live attenuated microorganisms.
 Killed vaccines: containing killed microorganisms.
 Recombinant vaccines: produced by genetic engineering.
 Toxoids: toxins produced by the bacteria after making them harmless.
N.B. Dangerous to give live vaccines to immunocompromised patients or
their close contacts.
A-Viral vaccines
 Live attenuated vaccines: e.g. measles, mumps, rubella, and Sabin
polio vaccine against poliomyelitis.
 Killed vaccines: e.g. Salk polio vaccine against poliomyelitis.
 Recombinant vaccines: hepatitis B vaccine (antigen = recombinant
HBsAg).
MMR = measles, mumps, and rubella vaccines.
OPV = oral polio vaccine = Sabin vaccine.
IPV = injection polio vaccine = Salk vaccine.
B-Bacterial vaccines and toxoids
 Live attenuated vaccines: e.g. BCG vaccine against TB (tuberculosis).

 Killed vaccines: e.g. pertussis (whooping cough) vaccine
 Toxoids: e.g. diphtheria toxoid, tetanus toxoid
DPT = diphtheria toxoid, pertussis vaccine, and tetanus toxoid.
DT = diphtheria and tetanus toxoids.
TT = tetanus toxoid

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What damages vaccines?
1. All vaccines lose their potency after a certain time, even with good care.
You know that time from the expiry date printed on the vaccine.
2. Heat and sunlight can damage vaccines, especially the live attenuated
ones.
3. Freezing damages vaccines, except the live attenuated ones.
4. Disinfectants or antiseptics can damage vaccines (such as spirits and
detergents) and antibiotics (such as streptomycin on BCG).

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Unit VII-Antineoplastics and

Immunosuppressants

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I-Cancer chemotherapy
A-Definitions:
 Tumor (neoplasm) consists of cells that proliferate independently of
the body’s inherent “building plan.”
 Malignant tumor (cancer) is present when the tumor tissue

destructively invades healthy surrounding tissue or when dislodged
tumor cells form secondary tumors (metastases) in other organs.
 Cancer chemotherapy consists of drugs which used in the treatment

of cancers. A cure requires the elimination of all malignant cells
(curative therapy). When this is not possible, attempts can be made
to slow tumor growth and thereby prolong the patient’s life or
improve quality of life (palliative therapy).
 Log-kill hypothesis: cytotoxic drugs act by first-order kinetics; that

is, at a given dose, they kill a constant fraction of the tumor cells
rather than a fixed number of cells.
B-Combination therapy:
The combined use of two or more drugs often is superior to single-agent
treatment in many cancers, and certain principles have been used in
designing such treatments:
 Each drug used in the combination regimen should have some
individual therapeutic activity against the particular tumor being
treated.
 Drugs that act by different mechanisms may have additive or
synergistic therapeutic effects. Tumors may contain heterogeneous
clones of cells that differ in their susceptibility to drugs. Combination
therapy will thus increase log cell kill and diminish the probability of
emergence of resistant clones of tumor cells.
 Drugs with different dose-limiting toxicities should be used to avoid
cumulative damage to a single organ.

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 Intensive intermittent schedules of drug treatment should allow time
for recovery from the acute toxic effects of antineoplastic agents,
primarily bone marrow toxicity. The use of non myelosuppressive
agents can be considered during the recovery period.
 Several cycles of treatment should be given, since one or two cycles
of therapy are rarely sufficient to eradicate a tumor. Most curable
tumors require at least six to eight cycles of therapy.
The chemotherapy of advanced Hodgkin’s disease is one of the best

examples of successful combination chemotherapy. Combination therapy
with the MOPP regimen (Mechlorethamine, Oncovin [vincristine],
Procarbazine, Prednisone), alternating with ABVD (Adriamycin
[doxorubicin], Bleomycin, Vinblastine, Dacarbazine), has resulted in cure
rates of 50 to 60%.
C-Cell cycle and anticancer therapy
Cell cycle consists of phases that all cells -normal and neoplastic- must
traverse before and during cell division.
 G1 (growth)
 S (synthesis of DNA)
 G2 (growth)
 M (mitosis: prophase–metaphase– anaphase–telophase).
 G0 (quiescent G1 phase)
G1 and G0 are of variable duration. Mitosis is usually shortest phase. Most
cells are in G0.
Rapidly dividing cells have a shorter G1.
Many of the effective anticancer drugs exert their action on cells traversing
the cell cycle (proliferating cells) and are called cell cycle-specific (CCS)
drugs. In most cases, they are also phase- specific; for example,
hydroxyurea and cytarabine kill only cells in the S-phase. Similarly,
bleomycin is most toxic to cells in G2- and early M-phases.

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A second group of agents called cell cycle-nonspecific (CCNS) drugs can
sterilize tumor cells whether they are cycling or resting in the G0
compartment. CCNS drugs can kill both G0 and cycling cells (although
cycling cells are more sensitive).
In general, CCS drugs are most effective in hematologic malignancies and in
solid tumors in which a relatively large proportion of the cells are
proliferating or are in the growth fraction. CCNS drugs are particularly
useful in low growth fraction solid tumors as well as in high growth fraction
tumors.

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II-Classification of drugs
A-Alkylating agents:
They are the largest class of anticancer agents. They are compounds that are
capable of introducing alkyl groups into nucleophilic sites on other
molecules within cells through the formation of covalent bonds.The
macromolecular sites of alkylation damage include DNA, RNA, and various
enzymes.
 Nitrogen mustards:
- Cyclophosphamide
- Chlorambucil
- Melphalan
- Ifosfamide
- Mechlorethamine hydrochloride.
 Alkyl sulfonates:
- Busulfan
 Nitrosoureas:
- Carmustine
- Lomustine
- Semustine
- Streptozocin.
 Ethylenimines :
- Thiotepa
 Triazenes:
- Dacarbazine
B-Antimetabolites:
 Folate antagonist:
- Methotrexate
 Purine analogues:
- mercaptopurine (6-MP),
- thioguanine,
- fludarabine,
- pentostatin,
- cladribine.
 Pyrimidine analogues:

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- fluorouracil (5-FU, 5-fluorouracil),
- cytarabine (cytosine arabinoside)
They are drugs structurally related to naturally occurring compounds, such
as vitamins, amino acids, and nucleotides.
These drugs can compete for binding sites on enzymes or can themselves
become incorporated into DNA or RNA and thus interfere with cell growth
and proliferation.
C-Antibiotics
 Anthracyclines:
- Doxorubicin,
- Daunorubicin,
- Idarubicin.
 Bleomycins: (bleomycin sulfate )
 Mitomycin (mitomycin C)
 Dactinomycin (actinomycin D)
 Plicamycin
D-Plant-derived products
 Vinca alkaloids:
- Vincristine
- Vinblastine
 Epipodophyllotoxins:
- Etoposide
- Teniposide
 Taxanes:
- Paclitaxel
E-Enzymes:
 L-Asparaginase
F-Hormonal agents
 Glucocorticoids.
 Androgens /antiandrogens
- flutamide
 Estrogens/ antiestrogens

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- tamoxifen citrate,
- estramustine phosphate sodium.
 Progestins
 Luteinizing hormone–releasing hormone (LH-RH) antagonists:
- buserelin,
- leuprolide
 Octreotide acetate
G-Miscellaneous agents
 Cisplatin (cis-platinum II)
 Procarbazine (N-methylhydrazine)
 Mitotane
 Hexamethylmelamine (HMM)
 Hydroxyurea
 Carboplatin
 Mitoxantrone
H-Monoclonal antibodies
 Bevacizumab
 Trastuzumab
 Rituximab
 Gemtuzumab
I-Immunomodulating agents
 Levamisole
 Interferons : (interferon alfa-2a, interferon alfa-2b)
 Interleukins: aldesleukin (interleukin-2, IL-2, Proleukin)
J-Cellular growth factors:
 Filgrastim,
 Sargramostim
III-Agents used in cancer
Ideal anticancer drugs would eradicate cancer cells without harming normal
tissues. Unfortunately, no currently available agents meet this criterion, and
clinical use of these drugs involves a weighing of benefits against toxicity in
a search for a favourable therapeutic index.

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1-Methotrexate:
Mechanism:
S-phase-specific antimetabolite. Folic acid analog that inhibits dihydrofolate
reductase, resulting in decreased DNA and protein synthesis.
Clinical use:
 Leukemias,
 Lymphomas,
 Choriocarcinoma,
 Breast carcinoma,
 Sarcomas.
 Rheumatoid arthritis,
 Psoriasis.
Toxicity:
 Bone marrow suppression -which is reversible with leucovorin
(folinic acid)
 Crystalluria.
2- 5-fluorouracil (5-FU):
Mechanism:
S-phase-specific antimetabolite. Pyrimidine analog, bioactivated to inhibits
thymidylate synthase, resulting in decreased DNA and protein synthesis.
Clinical use:
 Colon cancer and other solid tumors,
 Basal cell carcinoma (topical).
Synergy with methotrexate.

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Toxicity:
 Bone marrow suppression -which is NOT reversible with leucovorin-,
 GI irritation,
 Alopecia.
3-6-Mercaptopurine (6MP)
Mechanism:
Blocking purine synthesis.
Clinical use:
 Leukemias,
 Lymphomas (not Chronic lymphoid or Hodgkin’s lymphomas)
Toxicity:
 GI irritation
 Hepatotoxicity.
Metabolized
4-Busulfan
Mechanism:
Alkylating agent.
Clinical use:
CML (chronic myeloid lymphoma).
Toxicity:
 Pulmonary fibrosis
 Hyperpigmentation.
5-Cyclophosphamide
Mechanism:
Alkylating agent.

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It requires bioactivation by liver.
Clinical use:
 Non-Hodgkin’s lymphoma,
 Breast and ovarian carcinomas.
 Also an immunosuppressant.
Toxicity:
 Hemorrhagic cystitis
 Hepatotoxicity.
6-Nitrosureas
Mechanism:
Alkylating agent.
It requires bioactivation.
It crosses blood–brain barrier →CNS.
Clinical use:
Brain tumors.
Toxicity:
CNS toxicity (dizziness, ataxia).
7-Cisplatin:
Mechanism:
It acts like an alkylating agent.
Clinical use:
 Testicular, bladder, ovary, and lung carcinomas.
Toxicity:
 Nephrotoxicity
 Acoustic nerve damage.

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8-Doxorubicin (adriamycin)
Mechanism:
It intercalates in DNA creating breaks to decrease replication and
transcription and generate free radicals.
Clinical use:
 Hodgkin’s lymphoma (ABVD regimen),
 Myelomas
 Sarcomas
 Solid tumors (breast, ovary, lung).
oxicity:
 Cardiotoxicity (delayed congestive heart failure)
 Marked alopecia.
9-Bleomycin
Mechanism:
G2-phase-specific intercalates DNA strands, induces free radical formation,
causing strand breaks.
Clinical use:
 Testicular cancer
 Lymphomas.
Toxicity:
 Pulmonary fibrosis,
 Skin changes (blisters),
 Minimal bone marrow suppression.
10-Etoposide:
Mechanism:
G2-phase-specific inhibits topoisomerase II so that double-strand breaks
remain in DNA following replication, with subsequent DNA degradation.

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Clinical use:
 Oat cell carcinoma of the lung and prostate,
 Testicular carcinoma.
Toxicity:
 GI irritation,
 Alopecia.
11-Prednisone
Mechanism:
It may trigger apoptosis. It may even work on non-dividing cells.
Clinical use:
 Most commonly used glucocorticoid in cancer chemotherapy.
 Used in CLL (chronic lymphoid lymphoma), Hodgkin’s lymphomas
(MOPP regimen).
 Also an immunosuppressant used in auto immune diseases.
Toxicity:
 Immunosuppression,
 Cataracts
 Acne
 Osteoporosis
 Hypertension
 Peptic ulcers
 Hyperglycemia.
12-Tamoxifen/ raloxifene
Mechanism:
Estrogen receptor mixed agonist/antagonist that blocks the binding of
estrogen to estrogen receptors.

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Clinical use: Breast cancer.
Toxicity: may increase the risk of endometrial carcinoma via partial agonist
effects.
13-Vincristine (Oncovin) and vinblastine
Mechanism:
M-phase-specific alkaloid that binds to tubulin and blocks polymerization of
microtubules so that mitotic spindle can’t form.
Clinical use:
 Vincristine (Oncovin): Hodgkin’s lymphoma (MOPP regimen),
leukemias, Wilms’ tumor.
 Vinblastine: Hodgkin’s lymphoma (ABVD regimen), testicular
carcinoma, Kaposi’s sarcoma.
Toxicity:
 Vincristine: neurotoxicity (areflexia, peripheral neuritis).
 Vinblastine: bone marrow suppression, GI irritation, alopecia.
14-Paclitaxel
Mechanism:
M-phase-specific agent obtained from yew tree that binds to tubulin and
hyperstabilizes polymerized microtubules so that mitotic spindle can’t break
down (anaphase cannot occur).
Clinical use:
Ovarian and breast carcinomas.
Toxicity:
Bone marrow suppression and hypersensitivity.

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IV-Immunopharmacology
A-Idea about immune response
The immune system mediates the individual’s relationship with the
microbial environment.
It is divided into two functional divisions:
 Non-specific (innate) (natural) immune response:
It is the first line of defense against infectious agents.
 Specific (adaptive) (acquired) immune response; which is
subdivided into:
- Humoral immune response (antibodies formation by B-
lymphocytes).
- Cell mediated immune response by T- lymphocytes.
The essential difference between the two types of immunity lies in the
means by which microorganisms are recognized.
In innate immunity, glycolipids and macromolecules with repeat patterns

that are unique to infectious organisms are recognized by cell surface
receptors on macrophages, dendritic cells, natural killer (NK) and NK T
(NKT) cells, as well as by the complement system.
In acquired immunity, lymphocytes (B cells and T cells) use very specific
antigen receptors to recognize infectious agents and other antigens, either
directly or when processed by antigen-presenting cells (APCs), such as
dendritic cells. Thus, an interplay exists between innate and acquired
immunity at the level of the APC.
Once an otherwise healthy person has had an infection with bacteria or with
a virus, the immune system recognizes that pathogen and prevents its
recurrence. In addition, the immune system has the remarkable capacity to
discriminate between antigens, even if their structures are closely related.

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The immune response needs to be able to distinguish between self and non-
self antigens. Otherwise, T cells and antibodies would constantly be
attacking autologous cells, tissue components, or even commensal bacteria.
In the 1950s, Sir Frank Macfarlane Burnet first proposed that in the prenatal
state, the interaction of self- antigens with antigen-specific lymphocytes
leads to the elimination of self-reactive lymphocytes and hence to
immunologic tolerance. When immunologic tolerance breaks down, the
antibodies and sensitized (antigen-reactive) cells that are directed against
self-antigens cause autoimmune diseases.

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B-Specific immunosuppressive agents
1-Cyclosporine

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It binds to cyclophilins→ blocking the differentiation and activation of T
cells (mainly by inhibiting the production of IL-2 and its receptor).
Clinical use:
 It suppresses organ rejection after transplantation,
 Selected autoimmune disorders.
Toxicity:
 Nephrotoxicity
 Peripheral neuropathy
 Hyperglycemia
 Hyperlipdiaemia
 Hypertension,
 Gingival hyperplasia
 Hirsutism
2-Tacrolimus
Similar to cyclosporine; it binds to FK-binding protein, inhibiting secretion
of IL-2 and other cytokines.
Clinical use:
 Potent immunosuppressive used in organ transplant recipients (more
potent than cyclosporine).
Toxicity:
Similar to cyclosporine except gingival hyperplasia & hirsutism.
3-Rapamycin (Sirolimus)
It is structurally related to tacrolimus. It blocks IL-2-dependent T-cell
proliferation.

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Clinical use:
It is approved for use as an adjunctive agent in combination with
cyclosporine for prevention of acute renal allograft rejection.
Toxicity:
 Bone marrow suppression ( leucopenia, thrombocytopenia, anaemia),
 Diarrhoes,
 Rash,
 Hyperlipidaemia
4-Azathioprine:
It is a cytotoxic drug; metabolized to 6-Mercaptopurine that interferes with
the metabolism and synthesis of nucleic acid.
Toxic to proliferating lymphocytes after antigenic stimulus.
It affects all rapidly dividing cells.
Clinical use:
 Kidney transplantation
 Autoimmune disorders (including glomerulonephritis and hemolytic
anemia).
Toxicity:
 GI ulceration
 Diarrhea,
 Decreased wound healing
 Alopecia,
 Increased risk of infection,
 Increased cancer risk.
5-Other cytotoxic drugs:
 Cyclophosphamide
 Methotrexate

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6-Mycophenolate Mofetil
Mechanism:
It inhibits lymphocyte proliferation.
Clinical use:
In conjunction with cyclosporine and corticosteroids for prevention of organ
rejection in patients receiving allogeneic renal and cardiac transplants.
Toxicity:
GI side effects are most common (nausea, vomiting, diarrhoea).

7-Glucocorticoids:
 Prednisone
 Prednisolone
They inhibit cytokine gene expression;  IL-1 secretion & IL-2 synthesis &
release,  lymphocytes,  monocytes, and  macrophage function.
Clinical use:
 Used alone or in combination with other agents in the treatment of
autoimmune disorders and for the prevention of transplant rejection.
Toxicity:
 Immunosuppression
 Cataracts
 Acne
 Osteoporosis
 Hypertension
 Peptic ulcers
 Hyperglycemia.

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8-Monoclonal antibodies:
 Muromonab-(CD3)
It blocks antigen recognition by T-cell (CD3).
Clinical use:
Prevention of acute allograft rejection in kidney and hepatic transplants and
as prophylaxis in cardiac transplantation.
Toxicity:
 Fever
 Headache
 Dyspnoea
 Pulmonary edema
 Anaphylaxis.
9-Rho(D) Immune globulin
It is a preparation of human IgG that contains a high titer of antibodies
against the Rho (D) red cell antigen.
Clinical use:
Administer to Rh-negative mother within 72 hours of delivery of an Rh-
positive infant to prevent Rh hemolytic disease in future newborns (prevent
the mother from becoming sensitized to the Rh antigen by binding to and
destroying fetal red blood cells that have entered her blood).

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C-Idea about Immunostimulants
A number of disorders can be treated with immunostimulating agents (also
known as biological response modifiers or immunomodulating agents).
These conditions include immunodeficiency diseases, cancer, some types of
viral and fungal infections, and certain autoimmune disorders.
Immunostimulating agents are non specific; they cause general stimulation
of the immune response.
These drugs may work on cellular or humoral immune systems or both.
1-Bacillus Calmette-Guérin (BCG)
 It is a viable attenuated strain of Mycobacterium bovis.

 It stimulates T cells and natural killer cells, which in turn can kill
malignant cells.
 BCG immunotherapy has been most successful in the treatment of
bladder cancers.
 The most dangerous complications are severe hypersensitivity and
shock. Chills, fever, malaise, immune complex, and renal disease are
among the other side effects.
2-Levamisole:
 It was originally developed as an antihelminthic drug.
 It potentiates the stimulatory effects of antigens, mitogens,
lymphokines, and chemotactic factors on lymphocytes, granulocytes,
and macrophages. It has been shown to increase T cell–mediated
immunity.
 It has been used successfully in treating chronic infections. It also has
been approved for use in combination with fluorouracil in the
treatment of colorectal cancer.

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4-Thymic factors:
 Thymic humoral factor
 Thymosin fraction 5
 Thymodulin
 They are naturally occurring substances isolated from a calf thymus
extract that promote T-lymphocyte differentiation.
 They are used to enhance T-lymphocytic functions. Thymic factors
have been used with some success in clinical trials in patients with
severe combined immunodeficiency and viral disorders.
 Few major side effects have been reported, especially with purer
forms produced by genetic engineering. Crude thymic preparations
have produced allergic side effects in some patients.
5-Immune globulin:
 It is isolated from pooled human plasma.
 It is recommended in the treatment of primary humoral
immunodeficiency, congenital agammaglobulinemias, idiopathic
thrombocytopenic purpura, and autoimmune hemolytic anemia.
 The principal side effects are possible anaphylactoid reactions and
severe hypotension.
6-Cytokines :
Lymphokines
 Monokines
 The immune cell function is regulated by cytokines produced by
leukocytes or other supporting cells.
 With the advent of genetic engineering, cytokines can be produced in
pure form and in large quantities.
 Examples of some clinically important cytokines:
a. Interleukin-2 (IL-2)
- It promotes the proliferation, differentiation, and recruitment of
T and B lymphocytes, natural killer cells, and thymocytes.
- Recombinant IL-2 (rIL-2) is administered systemically as an
immunostimulating agent in patients with AIDS and to augment
specific antitumor immunity.
- Systemic administration of rIL-2 causes fever, nausea, vomiting,
fatigue, and malaise. Other adverse affects include flushing,

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diarrhea, chills, rash, edema, symptomatic hypotension, and
certain renal abnormalities.
b. Myeloid Colony–Stimulating Factors
- Recombinant granulocyte-macrophage colony–stimulating factor
(GM-CSF) (Sargramostim) and granulocyte stimulating factor
(G-CSF) (Filgrastim)
- They are cytokines, or growth factors, that support the survival,
clonal expansion, and differentiation of hematopoietic cells.
- In general they are indicated for acceleration of the recovery of
circulating white blood cells in patients who have depressed
hematopoiesis, as a result of either chemotherapy or congential
disorders of hematopoisis.
- Adverse effects include diarrhea, asthenia, rash, malaise, fever,
headache, bone pain, chills, and myalgia. Many of these effects
can be ameliorated by the administration of analgesics and
antipyretics.
c. Interferons
- Interferon-alpha (IFN-α): used clinically in treatment of chronic
hepatitis B and C, leukemias, melanoma.
- Interferon-beta (IFN-β): used clinically in treatment of multiple
sclerosis.
- Interferon-gamma (IFN- γ): used clinically in treatment of chronic
granulomatous disease.

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Unit VIII-Vitamins

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I-Introduction to vitamins importance and sources

Vitamins are a group of unrelated chemical substances that are essential in
small amounts for the regulation of normal metabolism, growth, and
function of the human body.
Not all of the vitamins can be synthesized in the body, and therefore, some
vitamins must be obtained from an external source, such as a proper well
balanced diet or dietary supplements.
Deficiency diseases can result from insufficient vitamin ingestion, irregular
absorption, or impaired metabolic use of these nutrients. Certain groups of
the population are particularly at risk, such as low-income families and
chronically ill patients.
Vitamin toxicity (Hypervitamiosis) can result from ingestion or
administration of excessive quantities of vitamins.
Generally the water-soluble vitamins are less toxic, since excess quantities
are usually excreted in the urine.
Excessive amounts of fat-soluble vitamins, however, are stored in the body,
which makes toxic levels of these vitamins easier to obtain.
Vitamins are usually classified as either fat soluble (vitamins A, D, E, and
K) or water soluble (vitamins B and C).
The fat-soluble vitamins are generally metabolized slowly and are stored in
the liver.
In contrast, the water-soluble vitamins are rapidly metabolized and are
readily excreted in the urine.

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II-Fat-soluble vitamins
A-Vitamin A (Retinol):
1-Sources:
 Animal foods (whole milk, liver, egg yolk, fatty fish and fish liver
oil).
 Plant foods (yellow, green, and orange vegetables and fruit especially
dark green leafy vegetables).
 Plant foods contain the provitamin carotene which converted in the
body into vitamin A.
2-Function:
 Constituent of visual pigments (retinal)

 Maintenance of the functional and structural integrity of epithelial
cells and cartilage
3-Deficiency:
 Night blindness and xerophthalmia,
 Hyperkeratosis and dry skin
 Arthralgia.
4-Toxicity:
 Fatigue
 Headaches
 Skin changes
 Alopecia
 Hepatosplenomegaly
 Teratogenicity.
B-Vitamin D (Calciferol)
 Ergocalciferol (D2)
 Cholecalciferol (D3).
Storage form (25-OH D3) and active form (1,25 (OH)2 D3).
1-Sources:
 Animal food (liver, egg yolk, fatty fish and fish liver oil).
 Others (exposure of the skin to ultra violet rays)

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2-Function:
It increases intestinal absorption of calcium and phosphate.
3-Deficiency:
 Rickets in children (bending bones)
 Osteomalacia in adults (soft bones)
 Hypocalcemic tetany and muscle weakness.
4-Toxicity:
 Hypercalcemia
 Loss of appetite.
C-Vitamin E (Tocopherol)
1-Sources:
 Animal food (liver, egg yolk)
 Plant food (plant oils; including wheat germ, rice, and leafy
vegetables).
2-Function:
Antioxidant .
3-Deficiency:
 Haemolytic anemia
 Areflexia
 Gate disturbance, .
4-Toxicity:
 Muscle weakness
 Fatigue
 Headache, and nausea.
D-Vitamin K (Menadione)
 Phylloquinone (K1)
 Menaquinones (vitamin K2)
 Menadione (K3).

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1-Sources:
 K1: dark green leafy vegetables (e.g. spinach).
 K2: biosynthesis by intestinal flora.
2-Function:
It is essential for the synthesis of proteins that are involved in the
coagulation of blood. The vitamin K–dependent clotting factors II, VII, IX,
X, and protein C and S.
3-Deficiency:
Hemorrhagic conditions
4-Toxicity:
Not been documented.

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III-Water soluble vitamins

A-Vitamin C (Ascorbic Acid)
Sources:
Fresh vegetables and fruits; especially citrus fruits, guava, and strawberries,
green pepper, tomatoes.
Function:
 Antioxidant and coenzyme in oxidation reactions.
 Essential for the maintenance of the ground substance that binds cells
together and for the formation and maintenance of collagen.
Deficiency:
 Scurvy (swollen gums and loose teeth, bruising, poor wound healing,
capillary fragility results in haemorrhages, increased liability to
infection).
Toxicity:
It may result in diarrhoea due to intestinal irritation, renal oxalate stones may
form in some patients.
B-Vitamin B-complex:
 The B vitamin group is made up of substances that tend to occur
together in foods and are given the collective name vitamin B
complex.
 The vitamins of the B group usually have to be converted to an active
form (coenzyme), and most of them play a vital role in intracellular
metabolism.
 The B vitamins are obtained from both meat and vegetable products,
except for vitamin B12, which occurs only in animal products. The
richest source of the B vitamin group is seeds, including the germ of
wheat or of rice.
 The effects of most vitamin B overdoses (toxicity) have not been
documented.

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1-Vitamin B1 (thiamine):
 Function: co-enzyme in carbohydrate metabolism.

 Deficiency:
- Beriberi (oedema, and heart failure, neurological symptoms
such as polyneuritis, anorexia, irritability, and mental
deterioration)
- Wernicke-Korsakoff syndrome (neurological symptoms such as
severe memory deficit, ataxia).
2-Vitamin B2 (Riboflavin):

 Deficiency:
- Ariboflavinosis (angular stomatitis, glossitis, cheilosis, corneal
vascularization, seborrheic dermatitis, peripheral neuropathy).
3-Vitamin B3 (Niacin; Nicotinic acid)
 Derived from tryptophan.

 Deficiency:
- Pellagra (diarrhea, dermatitis, dementia),
- Beefy glossitis.
 Toxicity:
- Flushing
- Pruritus,
- Gastrointestinal disturbances,
- Hepatic toxicity
4-Vitamin B5 (Pantothenate; Pantothenic acid)
 Function: it is an essential component of coenzyme A (CoA) for the

transport of acetyl and succinyl units.
 Deficiency:
- Dermatitis
- Enteritis,
- Alopecia,
- Adrenal insufficiency.

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5-Vitamin B6 (Pyridoxine)
 Function: co-enzyme in amino acid transformations and tryptophan-

niacin conversion.
 Deficiency:
- Neurological symptoms (sensory neuritis, mental depression,
and convulsions)
- Hypochromic sideroblastic anemia.
 Toxicity: peripheral neuropathy.
6-Vitamin B12 (Cobalamin)
 Function: co-enzyme in nucleic acid synthesis and essential for

erythropoiesis.
 Deficiency:
- Pernicious anemia (megaloblastic anemia and neurological
symptoms “peripheral neuropathy, optic atrophy, depression”)
- Glossitis.
C-Folic Acid (Folacin)
Function: co-enzyme in nucleic acid synthesis and protein metabolism and
essential for erythropoiesis.
Deficiency:
 Megaloblastic anemia
 Glossitis
 Diarrhea
 Neural tube defect in fetus.
D-Biotin
Function: co-enzyme in fatty acid synthesis
Deficiency:
 Anorexia
 Glossitis,
 Depression,
 Dry, scaly dermatitis.
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Recommended Daily Dietary All owances a
Fat-Soluble Vitamins
Age Vitamin Vitamin D Vitamin Vitamin

(Years) A
or Weight Height Protein E K
Categor Conditi (kg) (cm) (g) c -

y on RE)b TE)d
Infants 0.0-0.5 6 60 13 375 7.5 3 5
0.5-1.0 9 71 14 375 10 4 10
Childre 1-3 13 90 16 400 10 6 15

n
4-6 20 112 24 500 10 7 20
7-10 28 132 28 700 10 7 30
Males 11-14 45 157 45 1,000 10 10 45
15-18 66 176 59 1,000 10 10 65
19-24 72 177 58 1,000 10 10 70
25-50 79 176 63 1,000 5 10 80
77 173 63 1,000 5 10 80
Female 11-14 46 157 46 800 10 8 45

s
15-18 55 163 44 800 10 8 55
19-24 58 164 46 800 10 8 60
25-50 63 163 50 800 5 8 65
65 160 50 800 5 8 65
Pregnan 60 800 10 10 65
t
Lactatin 1st 6 months 65 1,300 10 12 65

g
2nd 6 months 62 1,200 10 11 65
Water-Soluble Vitamins

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Age Vitami Vitami Vitami
(Years) nC n B6 n B12
or Weig Heig Protei Thiami Riboflavi Niaci Folat
ht ht n n n n e
Conditi
Categor on (kg) (cm) (g) (mg) (mg) (mg) (mg (mg)
y NE)e
Infants 0.0-0.5 6 60 13 30 0.3 0.4 5 0.3 25 0.3
0.5-1.0 9 71 14 35 0.4 0.5 6 0.6 35 0.5
Childre 1-3 13 90 16 40 0.7 0.8 9 1.0 50 0.7

n
4-6 20 112 24 45 0.9 1.1 12 1.1 75 1.0
7-10 28 132 28 45 1.0 1.2 13 1.4 100 1.4
Males 11-14 45 157 45 50 1.3 1.5 17 1.7 150 2.0
15-18 66 176 59 60 1.5 1.8 20 2.0 200 2.0
19-24 72 177 58 60 1.5 1.7 19 2.0 200 2.0
25-50 79 176 63 60 1.5 1.7 19 2.0 200 2.0
77 173 63 60 1.2 1.4 15 2.0 200 2.0
Female 11-14 46 157 46 50 1.1 1.3 15 1.4 150 2.0

s
15-18 55 163 44 60 1.1 1.3 15 1.5 180 2.0
19-24 58 164 46 60 1.1 1.3 15 1.6 180 2.0
25-50 63 163 50 60 1.1 1.3 15 1.6 180 2.0
65 160 50 60 1.0 1.2 13 1.6 180 2.0
Pregnan 60 70 1.5 1.6 17 2.2 400 2.2

t
Lactatin 1st 6 months 65 95 1.6 1.8 20 2.1 280 2.6

g
2nd 6 months 62 90 1.6 1.7 20 2.1 260 2.6
a The allo wances, expressed as average daily intakes over time, are intended to provide for individual
variations among most normal persons as they live in the Un ited States under usual environmental
stresses. Diets should be based on a variety of common foods in order to provide other nutrients for
which hu man requirements have been less well defined.

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b Retinol equivalents (RE -carotene.
c IU of vitamin D.
d -TE). 1 mg d - -TE.
e Niacin equivalents. 1 NE (n iacin equivalent) is equal to 1 mg of n iacin or 60 mg of d ietary tryptophan.

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Unit IX-Locally Acting Drugs

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I-Skin and Scalp preparations

The patient should be warned that the locally acting agents are for external
use only.
The patient should be told to see his physician if the condition does not
improve and to avoid getting the prepared solution in contact with his eyes.
A-Emolients
They are oily or fatty substances which soften and protect the skin e.g.:
 Fixed oils (vegetable oils)

- Olive oil
- Cotton seed oil,
- Almond oil.
 Fats:
- Lard and wool fat.
 Waxes: they are esters of fatty acids with alcohol.
B-Astringents
They are agents that dry mucous secretions, shrink skin, and cause blanching
(whitening).
Astringents are used to reduce inflammation of mucous membranes, to
promote healing, and to toughen skin.
1-Aluminium acetate tablets:
 When these tablets are added to water, aluminium acetate solution is

prepared.
 This product is used as an astringent for inflammatory skin conditions
such as insect bites, poison ivy, and athlete’s foot.

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2-Calamine lotion (calamine and zinc oxide lotion):
 This product is used as an astringent and as a protectant (used to cover

and protect epithelial surfaces).
 Both these actions aid in reducing inflammation associated with
insect bites, poison ivy, and sunburn.
3-Phenolated and mentholated calamine lotion:
Phenol and menthol have been added to the calamine lotion because they
produce an antipruritic effect.
C-Counter-irritants
 Methyl salicylate (oil of wintergreen).

 Camphor, menthol, and chloroform linimets (alcoholic solution of
volatile oil).
They are irritating agents applied locally to the intact skin to block the deep
pain in muscles or viscera.
Pain stimulus arising from the irritated area of skin will occupy the same
segment of spinal cord that occupied by the deep pain and thus block it.
They also produce dilatation of local blood vessels → increase blood supply
to the affected area.
D-Keratolytics and keratoplastics
Keratolytics are agents that induce sloughing of cornified epithelium (horny
or hard layer of the skin).
Keratoplastic (mild keratolytic) effect is seen when the drug does not
produce a rapid destruction and sloughing, thereby softening the keratin and
loosening the cornified epithelium.
Keratolytic agents are used to remove warts and corns. They are also used in
the treatment of severe acne.

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Keratoplastic agents are used in the treatment of acne, eczema, psoriasis, and
1-Coal tar:
It is used as a keratoplastic in the treatment of eczema, psoriasis, and
2-Salicylic acid:
 It is used as a keratolytic in concentrations from 5% to 20%.

 It is used as a keratoplastic in concentrations from 1% to 2%.
3-Sulfur:
It is used as a keratoplastic in the treatment of acne and seborrheic
dermatitis.
4-Tretinoin (Retin A):
 It is used in the treatment of severe acne.

 The application of this agent to the skin will produce a horny layer of
skin that is more easily removed.
 This medicine should not be applied to windburned or sunburned skin.
It should not be applied to open wounds. Furthermore, the medication
should not be applied inside the nose, around the eyes, or around the
mouth. While the patient is using the medication, he should avoid
exposing the area being treated to too much wind or sun (or sun
lamp).
 Adverse effects of tretinoin include erythema, peeling, burning, and
stinging. These effects often decrease spontaneously with time and are
lessened by use of emollient. Photosensitivity occurs, with a resulting
greater potential for sunburn. Tretinoin, given orally, is highly
teratogenic.

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E-Antiseborrheics:
 Chloroxine
 Selenium sulfide
They are used in the management of dandruff and seborrheic dermatitis.
Seborrheic dermatitis is characterized by a yellowish and greasy scaling of
the scalp and/or mid-parts of the face (around eyebrows and nose) and ears.
The ideal antiseborrheic agent should be nontoxic, relieve pruritus (itching),
modify excessive dryness, and demonstrate wide antifungal and antibacterial
spectra.
The patient should be instructed not to use this medication if blistered, raw,
or oozing areas are present on the scalp and to keep the medication away
from the eyes.
F-Sunscreens:
Acute effects of sun exposure include sunburn and drug-induced phototoxic
reactions. Chronic effects include photoaging and skin cancer.
Sunscreens are topical agents that reduce the amount of ultraviolet radiation
(UVA, UVB) reaching the skin or block it altogether.
Topical sunscreens are divided into physical and chemical agents:
1-Physical sunscreens:
They contain large particulate ingredients that reflect and scatter UVA,
UVB, and visible light. These ingredients include titanium dioxide, talc,
magnesium oxide, zinc oxide, kaolin, ferric chloride, and ichthamnol. These
sunscreens are opaque and therefore frequently cosmetically unacceptable.
2-Chemical sunscreens:
They are transparent and absorb portions of ultraviolet radiation. p-
Aminobenzoic acid esters, cinnamates, and salicylates are effective UVB-
blocking agents. Benzophenones, anthranilates, and particularly
avobenzone, are effective UVA screens. Multiple chemical sunscreens
usually are combined in commercial products to provide broad-spectrum
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coverage. Protection against UVB is more effective than protection against
UVA.
The substantivity of a sunscreen is its resistance to removal by water. A
"water-resistant" sunscreen should continue to function after 40 minutes in
water; a "waterproof" sunscreen withstands 80 minutes in water. The vehicle
is important in determining these properties.
Toxicity:
Contact dermatitis and photocontact dermatitis occur rarely in most
individuals, but they are common in atopic individuals.
The alcohol or fragrance contents of some sunscreen products can be
irritating, which leads to poor compliance by some individuals.
G-Local antiseptics and disinfectants: see before.
H-Miscellaneous agents:
1-Hydroquinone
 Hydroquinone produces reversible depigmentation of the skin by

inhibiting the enzymatic oxidation of tyrosine to 3,4-
dihydroxyphenyalanine and substantial inhibition of other melanocyte
metabolic processes.
 It is indicated for the gradual bleaching of hyperpigmented skin in
conditions such as melasma, freckles, and senile lentigines.
 Exposure to ultraviolet radiation will cause repigmentation, so
hydroquinone is frequently combined with a broad-spectrum
sunscreen.
2-Minoxidil
 Topical minoxidil is the first FDA-approved medication for

stimulating hair growth.
 t is approved for the treatment of androgenetic alopecia in both males
and females.
 It induces proliferation of epithelial cells near the base of the hair
follicle and may induce vasodilation of scalp blood vessels.
 Allergic contact dermatitis and irritant reactions occur.
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3-Topical steroids, antihistamines, antibacterial, antiviral, and antifungal
agents

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II-Drugs used in treatment of psoriasis

Psoriasis is a chronic scaling skin eruption characterized by keratinocyte
hyperproliferation.
A-Acitretin:
 It is a metabolite of the aromatic retinoid etretinate.

 It is given orally in the treatment of psoriasis, especially pustular
forms.
 It probably promotes terminal differentiation in psoriasis by
normalizing expression of keratins by epidermal cells.
 Adverse effects attributable to acitretin therapy are hair loss, initial
cutaneous exfoliation, sticky skin, easy bruising, and liver function
abnormalities. It is also teratogenic.
 Acitretin must not be used by women who are pregnant or may
become pregnant while undergoing treatment or at any time for at
least 3 years after treatment is discontinued.. Patients must not donate
blood during treatment and for 3 years after acitretin is stopped.
B-Tazarotene:
 It is an acetylenic retinoid prodrug that is hydrolyzed to its active form

by an esterase.
 The precise mechanism of action in psoriasis is unknown but may
relate to both anti-inflammatory and antiproliferative actions.
 Adverse local effects include a burning or stinging sensation (sensory
irritation) and peeling, erythema, and localized edema of the skin
(irritant dermatitis). Potentiation of photosensitizing medication may
occur, and patients should be cautioned to minimize sunlight exposure
and to use sunscreens and protective clothing.
 It is absorbed percutaneously, and teratogenic systemic concentrations
may be achieved if applied to more than 20% of total body surface
area. Women of childbearing potential must therefore be advised of
the risk prior to initiating therapy, and adequate birth control measures
must be utilized while on therapy.

pharmacology
C-Calcipotriene:
 It is a synthetic vitamin D3 derivative.
 Effective in the treatment of plaque type psoriasis vulgaris of
moderate severity
 Adverse effects include burning, itching, and mild irritation, with
dryness and erythema of the treatment area. Care should be taken to
avoid facial contact, which may cause ocular irritation.
D- Psoralens and UVA ( PUVA):
 Photochemotherapy with psoralen and UVA (PUVA) has been
approved for the treatment of vitiligo and psoriasis.
 Psoralen e.g. methoxypsoralen (methoxsalen) is given orally or
applied locally 1 to 2 hours before UVA exposure to produce
photosensitivity.
 The therapeutic effects of PUVA in psoriasis may result from a
decrease in DNA-dependent proliferation after adduct formation.
However, alteration in the immune system caused by PUVA also may
play a role.
 PUVA promotes melanogenesis in normal skin. Pigmentation results
from the transfer of melanosomes from melanocytes to epidermal
cells.
 The major acute side effects of PUVA include nausea, blistering, and
painful erythema.
E-Coal Tar:
Coal tar ointment contains crude coal tar, usually 2% to 5%, dispersed in
petroleum jelly.
 Little is known about its mode of action, which may be related to
antimitotic effects.
 Coal tar has a limited effect when employed as the sole treatment for
psoriasis, and it is now mainly combined with daily UVB irradiation
for this indication (known as the Goeckerman regimen).
 Folliculitis is the primary side effect of coal tar. Irritation and allergic
reactions are rare.

pharmacology
F-Other drugs in severe cases
 Steroids
 Methotrexate
 Cyclosporin
The End

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PHARMACOLOGY

YEHIA HASSAN MOHAMED ELMALIK

 Drugs acting on the autonomic nervous system

 Central nervous system

 Drugs used for respiratory tract disorders

 Hormones and antagonists

 Analgesics, Antipyretics and Anti-inflammatory agents

 Drugs affecting renal and cardiovascular functions

 Drugs acting on the Blood and Blood Forming Agents

 Drugs used in Gastro-Intestinal diseases

 Chemotherapy of Parasitic Infections

 Chemotherapy of Microbial diseases

 Antineoplastics and Immunosuppressants

 Locally Acting Drugs

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Drug: may be defined as any substance or mixture of substances designed

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b. With parenteral medications, the absorption rate is

Active drugs active metabolite

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parenteral (injection through veins, Intravenous

topical (applied to surface of skin transdermal (skin surface)

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Factors affecting the metabolism of drug.

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(2) Physiological factors:

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I- Physiological functions of autonomic nervous system

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II- Neurotransmitters - Receptors

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 Nicotinic receptors at the  Nicotinic receptors at

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Vasoconstriction Inhibition of Tachycardia Vasodilatation

Increased closure of Relaxed uterine

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7- Salmeterol and Formoterol:

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2- Treatment of Benign Prostatic Hypertrophy:

B- β-adrenergic blocking agents:

2- Other Nonselective β antagonists

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5- Antagonists of both α and ß adrenoreceptors:

Labetolol and Carvedilol are reversible ß-blockers with concurrent α1-

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Nicotine has many undesirable actions. It is without therapeutic benefit and

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A- Nondepolarizing (competitive) blockers:

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I-Histamines and Antagonists