‘

‘KPHARMA’

PHARMACOLOGY

FIRST EXAM QUESTIONS

1a. Sources of medical agents
-Plant Sources:
a) Alkaloids:- morphine, atropine, reserpine and ephedrine
b) glycosides:- digoxin and digitoxin
c) volatile oils:- clove oil, eucalyptus oil
d) resins:- tincture benzoin

-Animal sources : insulin , heparin and antisera .

- Human cells: urokinase (thrombolytic) {neonatal kidney cells}

- Mineral/ Earth sources: Iron is used in treatment of iron deficiency anemia. Mercurial salts
are used in Syphilis. Fluorine and borax have antiseptic properties.

- Microorganism: Penicillium notatum is a fungus which gives penicillin. Actinobacteria give

Streptomycin.

- Semi Synthetic sources: When the nucleus of drug obtained from natural source is
retained but the chemical structure is altered, we call it semi-synthetic.
Examples hydromorphone and hydrocodone

- Synthetic : aspirin and paracetamol

- Recombinant DNA technology: recombinant Hepatitis B vaccine, recombinant insulin.

2a. Main principles and methods of medical agents testing.

Principles of Medical agents testing :-
 It should be available in a form in which quality, including bioavailability and stability
on storage doesn’t get affected.
 Its choice should depend upon pattern of prevalent diseases; availability of facilities
and trained personal; financial resources; genetic, demographic and environmental
factors
 In case of two or more similar medicines, choice should be made on the basis of their
relative efficacy, safety, quality, price and availability. Cost-benefit ratio should be a
major consideration.
 Choice may also be influenced by comparative pharmacokinetic properties and local
facilities for manufacture and storage.
‘KPHARMA’
 Preclinical testing includes biochemical-pharmacological investigations, toxicological
investigations, study of pharmacokinetics and pharmaceutical technology (methods of drug
formulation).

Clinical testing starts with:

Phase I. During this phase the future drug is studied on healthy subjects and seeks to
determine whether effects observed in animal experiments also occur in humans.

Phase II potential drug is tested on selected patients for therapeutic efficacy in those
diseases for which it is intended.

In Phase III the drug is tested on large groups of patients and compared with standard
treatments. During clinical trials many drugs are revealed to be unusable.

3a. General principles of preclinical study of drugs.

Before testing drug in people, researchers must find whether the drug is causing toxicity or not.
It includes :
 Invitro (outside the body in controlled conditions.)
 In-vivo (in the living body using lab animals.)

– Identification of the active ingredient(s).

– Analysis of biological effects (Pharmacodynamics) of individual ingredients and of their fate in
the body (pharmacokinetics).
– Ensuring a precise and constant dosage in the therapeutic use of clinically pure constituents,
– The possibility of chemical synthesis (which affords independency from limited natural
supplies.).

4a. General principles of clinical trials of drugs.

Researchers gather information of drug (by experiment) such as :

 How it absorbs, Distributed, Metabolized & Excreted.
  Its benefits and mechanism of action.
 The best way (route) to give medicine & best dosage
 Side effect
 How it interact with other drugs
 Its effectiveness in comparison with similar drug.

Trial Rationale (it is important to justify the need for the proposed trial, to identify the
population of interest, and to determine the disease or biomarker prevalence in this
population. When the disease is rare or a targeted subgroup is of interest, then specific study
designs for these settings may need to be considered.)

Outcome of interest (Trial outcomes can be either health or treatment-related. Examples of

health outcomes include quality of life, symptoms, adverse events, and patient-reported
outcomes. Treatment outcomes include assessing the safety or efficacy of the intervention;
examples include tumor shrinkage, hematologic outcomes, intermediate, or surrogate
outcomes, time-to-event outcomes (e.g., overall survival or progression-free survival), and
surgical outcomes. )

Statistical Design (Estimating treatment effect is a common goal of many studies.)

Sample size collection (determine the number of patients needed to be enrolled in the study
to provide sufficient information to address the primary objectives.)

Monitoring & stopping rule (it is important to decide the number and timing of analyses to
be conducted before the completion of data collection and build this as part of the design.
Furthermore, it is important to specify parameters for all stopping rules for stopping the trial
early.)

Simulation studies (valuable tool for evaluating different trial designs and scenarios without
exposing patients to ineffective or harmful therapy or incurring the high financial costs
associated with running an actual trial.)

5a. Pharmacokinetics of drugs.

Pharmacokinetics of drug includes :-

a) Absorption b) Distribution c) Metabolism d) Excretion

Absorption is movement of drug from site of administration into the blood stream . It
involves interaction of drug through various biological membranes made up of lipid bilayer
by:
1. Passive diffusion (most common) - mainly lipid soluble drugs are absorbed through this
mechanism.

2 . Active transport:- Drug moves from lower to higher concentration .

E.g. transport of sympathomimetic amines into neural tissues and transport of choline
into cholinergic neurons. Two types:- primary and secondary.

3. Facilitated diffusion:- Carrier mediated transport which does not require energy .
Transport is from higher to lower concentration.
E.g. Transport of glucose across muscle cell membrane by transporter GLUT 4 .

4. Filtration:- depends on molecular size and weight of the drug .

5. Endocytosis :- Drug is taken up by the cell through vesicle formation.

Distribution is reversible transfer of drugs between body fluid compartments . After

absorption a drug enters the systemic circulation and is distributed in the body fluids.

Metabolism Drug metabolism reactions are grouped into 2 phases :-

Phase 1 reactions- Oxidation , reduction , hydrolysis, cyclization and decyclization
Phase 2 reactions- Glucuronidation (most common) , acetylation , sulphation , methylation,
glycine conjugation .

Excretion is removal of drug and its metabolite from the body . Main channels of excretion
are :-
1. Kidney - The processes involved in the excretion of drug via kidney are:
a) glomerular filtration
b) passive tubular reabsorption
c) active tubular secretion
2. Lungs - Alcohol and General anesthetics like halothane
3. Faeces - Drugs like purgatives e.g. senna and cascara
4. Bile - Tetracyclines
5. Skin - Metals like arsenic and mercury
6. Saliva - potassium iodide , phenytoin , lithium and metronidazole
7. Milk - Drugs taken by lactating mother may appear in milk like amiodarone .

6a. Pharmacodynamics of drugs.

Pharmacodynamics covers all the aspects about what the drug does to our body .

Pharmacodynamics describes:

Effects:-
1 Stimulation- adrenaline stimulates the heart resulting in an increase in heart rate .

2 Depression - Alcohol, barbiturates and general anesthesia depress the CNS

3 Irritation - Some agents on topical application can cause irritation of the skin and adjacent
tissues like eucalyptus oil, methyl salicylate etc.
4 Cytotoxic - Drugs are selectively toxic for the infecting organism/ cancer cells
e.g. antibiotics/ anticancer drugs

5 Replacement- When there is a deficiency of endogenous substances, they can be

replaced by drugs, e.g. insulin in diabetes mellitus, thyroxine in cretinism and myxedema,
etc.

The mechanism of action - These are events in cells caused by the drug. Medicinal
substances realize their action by:
 changing of the enzymes activity (e.g. neostigmine as acethylcholinesterase
inhibitor)
 interaction with receptors (e.g. atropine as M-cholinoblocker) influence on ion
channels (e.g. local anesthetics)
 influence on the transport systems
 the antimetabolic mechanism (e.g. methotrexate as folate antagonist) the action at
the genes level (e.g. anti-cancer drugs).

Drugs interactions - Two types :-

Pharmaceutical
(before the administration, outside
the body)
1. Physical (changes in agregate
state of drugs)
2. Chemical (chemical reac-
tions between the drugs).
Pharmacological
(after the administration, inside the
body)
1. Pharmacokinetic (interaction
during absorption, dis- tribution,
biotransformation, and excretion)
2. Pharmacodynamic (intraction in
tissues during binding to receptors).

=>Doses
=>Dose-effect dependence
=>Factors influencing a drug action.

7a. Routes of administration of the drugs.

There can be two routes for administration: Local and Systemic.
Local Routes: The drug is applied only on the required area. It is an easy method and have
low systemic effects.
 Topical use: The drug is applied locally on the area on the mucous membrane or
skin.
Example:
a) Oral: suspensions, cream, ointments can be used. {Nystatin and clotrimazole}
b) Rectum and anal canal: suppositories and enemas are used.
c) Eyes, ears and nose: drops, ointments can be used {gentamicin drops}
d) Skin: anesthetic creams used for anesthesia

Systemic routes: by this route drug can entre the blood and can cause systemic actions. Two
types- Enteral and Parenteral.
  Enteral route: has three types—oral, sublingual and rectal.
- Oral: Tablet, capsule and syrups can be used. Eg. Paracetamol
Advantages: safe, good for repeated use, painless
Disadvantages: not be used for emergency, drugs can be metabolized rapidly and have low duration

- Sublingual: the drug is kept under the tongue or in buccal area and is mixed in
the blood. Ex- nitroglycerin in angina attack and buprinorphine in myocardial
infraction.
Advantages: quick action, good, safe
Disadvantages: irritant, lipid- insoluble drug, bad taste.

- Rectal: liquid or solids are used, enemas and suppository. Ex- indomethacin for
rheumatoid arthritis.

 Parenteral route
These include inhalation and injections.

- Inhalations: volatile liquids and gases. Ex- drugs foe general anesthesia.

- Intravenous injections: dopamine infusion in cardiogenic shock, morphine in

myocardial infraction.

- Intra muscular: paracetamol, diclofenac.

- Intradermal injections: vaccines like BCG (Tb vaccine)
- Subcutaneous inj.: adrenaline, insulin
Advantages: quick onset, emergency use, used for unconscious patient, not absorbed or digested.
Disadvantages: require aseptic conditions, can cause injury to skin or vessels, painful, expensive

8a. Routes of drugs excretion.

Routes of drugs excretion are :-
1. Kidney - The processes involved in the excretion of drug via kidney are:
a) glomerular filtration - Drugs with small molecular size are more readily filtered. The
extent of filtration is directly proportional to the glomerular filtration rate (GFR) and to the
fraction of the unbound drug in plasma.

b) passive tubular reabsorption - The main factor affecting passive reabsorption is the pH of
renal tubular fluid and the degree of ionization. Strongly acidic and strongly basic drugs
remain in ionized form at any pH of urine, hence excreted urine.

c) active tubular secretion - It is a carrier-mediated active transport which requires energy.

Active secretion is unaffected by changes in the pH of urine and protein binding. Most of the
acidic drugs (e.g. penicillin, diuretics, probenecid, sulphonamides, etc.) and basic drugs (e.g.
quinine, procaine, morphine, etc.) are secreted by the renal tubular cells.

2. Lungs - Alchohol and General anesthetics like halothane

3. Faeces - Drugs like purgatives eg senna and cascara

4. Bile - Tetracyclines

5. Skin - Metals like arsenic and mercury

6. Saliva - potassium iodide , phenytoin , lithium and metronidazole

7. Milk - Drugs taken by lactating mother may appear in milk like amiodarone.
They have acid pH so the basic drugs like tetracyclines remains ionised and can affect the
breast-fed child.

9a. Mechanisms of drugs absorption at different routes of administration.

The movement of drug from the site of administration to the blood stream is called
absorption.

 Oral administration:- first pass metabolism can occur to the drugs. They are first
exposed to the liver and may be extensively metabolised before reaching the rest of
the body.

 A drug administered by intravenous route bypasses the process of absorption as it

directly enters the circulation. Some drugs are highly polar compounds, ionize in
solution and are not absorbed through GI tract, hence are given parenterally, e.g.
gentamicin.
 Drugs like insulin are administered parenterally because they are degraded in the GI
tract on oral administration.

During the absorption drug crosses cell membranes by 4 ways- passive diffusion, filtration,
active transport, and endocytosis.
- Passive diffusion is directed down concentration gradient. It does not require
energy or carrier and is not saturable
- Facilitated diffusion (or filtration) also is down gradient and energy independent,
but needs carrier and is saturable.
- Active transport is against gradient, needs energy ATP and carrier, it is saturable.
- Endocytosis is the process by which cells take in substances from outside of the
cell by engulfing them in a vesicle.

Factors influencing absorption are: Chemical structure, Water- or lipid-solubility, Ionization,

A medicinal form, The route of administration, State of tissues in the site of administration.

10a. Factors affecting gastrointestinal absorption of drugs.

Factors that influence the absorption of drugs in digestive tract are :-

1. Physicochemical properties of the drug:

 a). Physical state: Liquid form of the drug is better absorbed than solid formulations.

b). Lipid-soluble and unionized form of the drug is better absorbed than water-
soluble and ionized form.

C). Particle size: Drugs with smaller particle size are absorbed better than larger
ones, e.g. microfine aspirin, digoxin and griseofulvin are well absorbed from the gut
and produce better effects. Some of the anthelmintics have larger particle size. They
are poorly absorbed through gastrointestinal (GI) tract, hence they produce better
effect on gut helminths

d). Formulations: Pharmacologically inert substances like lactose, starch, calcium

sulphate, gum, etc. are added to formulations as binding agents. These are not
totally inert and may affect the absorption of drugs, e.g. calcium reduces the
absorption of tetracyclines.

2. Route of drug administration

3 Ph and ionisation :- Strongly acidic and strongly basic drugs remains ionised at all ph and
hence are poorly absorbed.

4. Blood flow to the absorption site: Blood flow to the intestine is higher than the flow to
the stomach, due to this absorption from the intestine is favored over that from the
stomach.

5. Total surface area available for absorption: The intestine has a surface area greater than
the stomach, because of the presence of microvilli. It makes absorption of the drug across
the intestine more efficient.

6. Contact time at the absorption surface: If a drug moves through the GI tract quickly
(during diarrhea), it is not well absorbed.

7. Food - Presence of food in the stomach can affect absorption of some drugs like
rifampicin , levodopa etc . Milk decreases the absorption of tetracyclines.

8. Presence of other drugs - Concurrent administration of two or more drugs may affect
their absorption, e.g. ascorbic acid increases the absorption of oral iron. Antacids reduce the
absorption of tetracyclines.

11a. Drug distribution.

It is the process by which a drug leaves the blood stream and enters the intersticium
(extracellular fluid or the cells of the tissues) Distribution depends on:

 The drug structure

  The binding of drugs to plasma proteins

 The blood flow

 The capillary permeability

(blood-tissue barriers, e.g. the blood-brain barrier, placental barrier). The transfer of drugs into
the brain is regulated by the blood-brain barrier. The capillary membrane between the plasma
and brain cells is much less permeable to water-soluble drugs than is the membrane between
plasma and other tissues. The blood vessels of the fetus and mother are separated by a number
of tissue layers that collectively constitute the placental barrier. Drugs that traverse this barrier
will reach the fetal circulation. The placental barrier, like the bloodbrain barrier, does not
prevent transport of all drugs but is selective, and factors that regulate passage of drugs through
any membrane are applicable here.

12a. Concept of specific receptors, agonists and antagonists.

Specific receptors are macromolecules that can be present either on the cell surface,
cytoplasm or in the nucleus and have narrow or limited action like these receptors will bind
only to their corresponding molecules and not to other types, thus they have specificity for
their molecules.

Agonist: A drug that is capable of producing pharmacological action after binding to the
receptor is called an agonist. Agonist has high affinity + high intrinsic activity (e.g. morphine
and adrenaline).
There are also partial agonist and inverse agonist.
Partial agonist:- drug that bind to receptor but produces very low effect or only partial
effect. Ex- pinodol

Inverse agonist:- It has full affinity towards the receptor but produce effect opposite to that
of agonist.
Ex- beta-carbolines produces anxiety and convulsions on benzodiazepine receptors.

Antagonist: A drug that prevents binding of agonist to its receptor or blocks e effect/s is
called an antagonist. It does not by itself produce any effect. Competitive antagonist has
high affinity without intrinsic activity (e.g. naloxone is an antgagonist of opioid receptors,
others atropine, anaprilin). It produces receptor blockade.
Antagonism can be of 4 types- physical, chemical, functional, receptor antagonism.

13a. Drug bioavailability.

BIOAVAILABILITY It is the fraction of a drug that reaches systemic circulation from a given
dose.
 Intravenous route of drug administration gives 100% bioavailability as it directly
enters the circulation.
 The term bioavailability is used commonly for drugs given by oral route. If two
formulations of the same drug produce equal bioavailability, they are said to be
bioequivalent. If formulations differ in their bioavailability, they are said to be
bioinequivalent.
 Factors affecting bioavailability :-
- The factors which affect drug absorption (physico- chemical properties of the
drug, route of drug administration, pH and ionization, food,presence of other
drugs) also affect bioavailability of a drug .

- Other factors are first pass metabolism( When drugs are administered orally,
they have to pass via gut wall to portal vein then liver and then to systemic
circulation .
- During this passage, certain drugs get metabolized and are removed or
inactivated before they reach the systemic circulation. This process is known as
first-pass metabolism. The net result is a decreased bioavailability) and hepatic
diseases.

- Hepatic disease: these decreases the drug metabolism so there is increase in

bioavailability of drug to undergo first pass metabolism. Ex- propranolol.

- Enterohepatic cycling: increases bioavailability

14a. Drug metabolism.

Main organ of drug metabolism is liver.

The general principal of biotransformation is the metabolic conversion of drug molecule to more
water-soluble metabolites that are more readily excreted. Biotransformation of an active compound
may lead to formation of metabolites that also have pharmacologic actions.

Some compounds are converted to toxic metabolites (N-acetyl-p-benzoquinone-imine (NAPQI).)

example: ACETAMINOPHEN (has hepatotoxic potential).

Biotransformation is realized in 2 stage

STAGE 1- Reaction are Non-synthetic and include oxidation,reduction, hydrolysis

 MICROSOMAL METABOLISM: In microsomal oxidase reductase; There will be participate of

enzyme cytochrome P450which are localized in smooth endoplasmic reticulum. Oxidationwill
include hydroxylation and dealkylation.

 NON MICROSOMAL METABOLISM: Hydrolysis will involvewater molecule with subsequent

bond breakage, includes Esterase and Amidase.

 Monoamine oxidase: metabolism of endogenous amine neurotransmitter (DOPAMINE,

NOREPINEPHRINE, ANDSEROTONIN); Metabolism of exogenous compounds (TYRAMINE).

 Alcohol metabolism: Alcohols are metabolized to Aldehydes andthen to acids by

dehydrogenase. –

The result of stage 1 is the formation of active or inactiveproducts which enters the 2 stage reaction.

Inducers of microsomal oxidation- Drugs which increase the activity of microsomal enzyme in liver
e.g. phenobarbital, carbamazepine, St.john wartz
Inhibitors of microsomal oxidation- drugs which decrease the activity of microsomal enzyme in liver
e.g. metronidazole. Grapefruit, Azol antifungals,

STAGE 2- Reaction are synthetic Conjugation with endogenous compounds like glucuronic
and sulfuric acid; methylation; acetylation via activity of Transferase. Result in formation of
inactive metabolites excreted from body.

- GLUCURONIDATION: Catalyzed by microsomal enzymes, dominates at high substrate

concentration, may undergo enterohepatic cycling (drug: Glucuronide— intestinal bacterial
glucuronidase--- free drug).{ENZYME (UDP GLUCURONYL TRANFERASE) ----- (REDUCED ACTIVITY IN
NEONATES, CHLORAMPHENICOL AND GRAY BABY SYNDROME). (DRUGS: ASPIRIN, PARACETAMOL,
METRONIDAZOLE, MORPHINE)}

- ACETYLATION: involves drug with Amino or Hydrazine groups; SULFONAMIDES, PROCAINAMIDE,

DAPSONE),genetic polymorphism

- GLUTATHIONE: Involve EPOXIDE, QUINONE, Toxic metabolites of PARACETAMOL, ETHRACRYNIC

ACID. Enzyme (GLUTATHIONE S.TRANSFERASE.)

15a. Accumulation of drugs.

Accumulation is the accumulation of the drug or its effects, it can be divided into
functional(accumulation of antidepressant) and material (accumulation of digoxin).

Material accumulation is accumulation of drug that are slowly excreted from the organism.
Functional accumulation is accumulation of drug effect it means presence of drug effect
after its excretion (alcohol, caffeine)
The accumulation of drugs in tissue or body compartment can increase drug action because
the tissue releases the accumulated drug and the concentration of plasma drug decreases.
When doses are repeated a drug can accumulate in the body until dosing stop, this is
because it takes time to get rid of a drug from the body.
Drugs may also accumulate in specific organs by active transport or get bound to specific
tissue constituents. Drugs sequestrated in various tissues are differentially distributed, tend
to have large volume of distribution and long duration of action. Some may exert local
toxicity due to high concentration.
e.g. tetracyclines on bone and teeth, chloroquine on retina, streptomycin on vestibular
apparatus, emetine on heart and skeletal muscle.

16a. Types of therapeutic and toxic doses. Therapeutic index of drugs.

A dose is quantity of medicine prescribed to be taken at a given time or it is the amount of
drug administered into the body.
Therapeutic doses – the dose which has therapeutic action.
MINIMAL DOSE: it is the lowest dose level of drug induced that provide clinically significant
response in average efficacy.
EFFECTIVE DOSE: is an amount of dose that produce therapeutic response or desired effect
in just some fraction in patient.

MAXIMAL DOSE: it is the highest quantity of drug that an patient can take safely within a
given period of time.

Toxic– the dose which causes toxic action.

MINIMAL TOXIC DOSE: is a smallest dosage of a drug that will produce signs and symptoms
of toxicity.
MEDIAN LETHAL DOSE: it is an amount of dose when given to a group of living beings for a
specific disease will cause toxicity in 50% cases.
MAXIMAL LETHAL DOSE: it is an amount of drug which will cause death due to toxicity.
Toxicity may result from extension of the therapeutic effect itself,
e.g. coma by barbiturates, complete A-V block by digoxin, bleeding due to heparin.
Another action of the drug can also be responsible for toxicity,
e.g.— • Morphine (analgesic) causes respiratory failure in overdosage.
• Imipramine (antidepressant) overdose causes cardiac arrhythmia.
• Streptomycin (antitubercular) causes vestibular damage on prolonged use

Single dose: for single administration, daily dose: for the day of treatment, total dose : for the course of treatment.

Threshold: minimal dose which begins to act.

Mortal: the dose which causes the death of animals in experiments.

Striking dose: a large dose at the start of treatment.

Supporting dose: an individual dose for supporting a therapeutic effect during long-term treatment.

Therapeutic index: It is the ratio of the dose that produces toxicity to the dose that produces
a clinically desired/effective response(TD50/ED50).
It is determined by measuring the frequency of desired response and toxic response at
various doses of drug.e.g; warfarin (small therapeutic index; at higher doses high degree of
anticoagulation occurs that results in hemorrhage.
-penicillin (large therapeutic index; its bioavailability does not critically alter the
therapeutic/clinical effects.)

17a. Types of pharmacological effects.

Therapeutic effect: effects for which the drug was intended and show its best action. eg.
Effect of salbutamol on asthma.
-Side effects: are non-useful effects of drugs in the therapeutic doses.
-direct toxic effects e.g., Digoxin toxic effect (headache, blurred vision, hallucination
etc.),
- allergic effects of all drugs (e.g., Metoprolol causing bronchospasm, )
- embryotoxic, fetotoxic and teratogenic effects as a negative influence on the
 embryo and the fetus during pregnancy (e.g., hypoplasia of tooth enamel caused by
tetracycline),
- cancerogenic and mutagenic action as the ability to provoke the development of
malignant tumors (e.g. secondary malignancy caused by leukopoiesis inhibitors),
- idiosyncrasy as abnormal reaction occurred after the first drug administration and
caused by genetic factors (e.g. hemolysis of erythrocytes after the use of quinine in
patients deficient on glucose-6-phosphate dehydrogenase)

Effects of repeated doses of drugs:

- Accumulation (material and functional) is the accumulation of the drug or its effects
(material accumulation of digoxin, functional accumulation of antidepressant).

- Tolerance: decrease of drugs action after its repeated administration (tolerance to

hypnotics, laxatives, nitroglycerine).

- Tachyphylaxis: rapid form of tolerance developing during the first day of treatment: e.g.,
tachyphylaxis to ephedrine.
- Drug dependence is irresistible aspiration to take the drug for euphoria or improvement of
condition.
There are two types of drug dependence:
Physical dependence – if the patent wants to take the drug for altering general state and
mood. It is characterized by abstinence. Abstinence is a phenomena of deprivation. Ethyl
alcohol and narcotic analgesics may cause physical dependence.
Psychological dependence – if the patient wants to take the drug for altering the mood (for
euphoria). Such kind of drug dependence is caused by psychomotor stimulants.

18a.Role of chemical structure, physical and chemical properties in the action of drugs on
an organism.
Physicochemical properties has all aspects of drug action and are critical for solubility,
permeability and successful formulation.
Specific physicochemical properties which are important to oral drugs are size, lipophilicity,
ionization, hydrogen bonding, polarity, aromaticity and shape.
Most drugs exert their effects, both beneficial and harmful, by interacting with receptors
(that is, specialized target macromolecules) present on the cell surface or within the cell.
The drug–receptor complex initiates alterations in biochemical and or molecular activity of
a cell by a process called signal transduction.
The physical structure of drug whether liquid, solid, or gas would determine how the drug
will be absorbed, distributed, metabolized and eliminated by the body.
The chemical structure would determine which bond need to be broken to allow the drug
to assimilated and catalyzed in the body.
19a. Dependence of pharmacological effect from dose (concentration) of medication.
Drug dependence is a state in which use of drugs for personal satisfaction is higher priority
than other basic needs, with the risks to health.
 Two types of drug dependence:-- psychological and physical
Psychological dependence It is said to have developed when the individual believes that
optimal state of wellbeing is achieved only through the actions of the drug. The subject feels
emotionally distressed if the drug is not taken. Reinforcement is the ability of the drug to
produce effects that the user enjoys and which make him/her wish to take it again or to
induce drug seeking behaviour. Certain drugs (opioids, cocaine) are strong reinforcers.
Physical dependence It is an altered physiological state produced by repeated
administration of a drug which becomes necessary to continue taking the drug to maintain
normal physiological condition. Discontinuation of the drug results in a characteristic
withdrawal (abstinence) syndrome.
Drugs producing physical dependence are— opioids, barbiturates and other depressants
including alcohol and benzodiazepines.
Drug abuse Refers to use of a drug by self-medication in a manner and increased amount
from the normal concentration. This can be social disapproval of the manner and purpose of
drug use.
The two major patterns of drug abuse are:

a. Continuous use: The drug is taken regularly, the subject wishes to continuously remain under the influence of
the drug,
e.g. opioids, alcohol, sedatives.

b. Occasional use: The drug is taken off and on to obtain pleasure or high, recreation (as in rave parties) or
enhancement of sexual experience, e.g. cocaine, amphetamines, psychedelics, binge drinking (alcohol),
cannabis, solvents (inhalation), etc.

Drug addiction It is a pattern of compulsive drug use characterized by overwhelming

involvement with the use of a drug. Procuring the drug and using it takes precedence over
other activities. Even after withdrawal most addicts tend to relapse. Physical dependence,
though a strong impetus for continued drug use, is not an essential feature of addiction.
Amphetamines, cocaine, cannabis, are drugs which produce addiction but little/no physical
dependence.
Drug habituation It denotes less intensive involvement with the drug, so that its withdrawal
produces only mild discomfort. Consumption of tea, coffee, tobacco, social drinking are
regarded habituating, physical dependence is absent.

20a.Drug interactions. Synergism, its types and practical significance.

When the action of one drug is facilitated or increased by the other, they are said to be
synergistic. By this process, a drug can have more potent action than it could have
individually.
Synergism can be additive and suppraaditve.

 Additive
The effect of the two drugs is in the same direction and simply adds up:
 Aspirin + paracetamol as analgesic/ antipyretic
Nitrous oxide + halothane  as general anaesthetic
Amlodipine + atenolol  as antihypertensive
Glibenclamide + metformin as hypoglycaemic
Ephedrine + theophylline as bronchodilator

 Suppradditive (potentiation)
The effect of combination is greater than the individual effects of the components:

DRUG BASIS OF
PAIR POTENTIATION

Acetylcholine + Inhibition of
physostigmine break down

Levodopa + Inhibition of
carbidopa peripheral
metabolism

Adrenaline + Inhibition of
cocaine neuronal uptake
21a. Drug interactions. Antagonism, its types and practical significance.

In antagonism, the effect of one drug is decreased or abolished in the presence of another
drug.
Types:-
1. Physical antagonism: The opposing action of two drugs is due to their physical property,
e g. adsorption of alkaloids by activated charcoal- useful in alkaloid poisoning.

2. Chemical antagonism: The opposing action of two drugs is due to their chemical
property,
Example- • KMnO4 oxidizes alkaloids—used for gastric lavage in poisoning.
• Nitrites form methaemoglobin which reacts with cyanide radical.

3. Physiological (functional) antagonism: The two drugs act on different receptors or by

different mechanisms, but have opposite overt effects on the same physiological function,
i.e. have pharmacological effects in opposite direction.
Example- • Histamine and adrenaline on bronchial muscles and BP.
• Hydrochlorothiazide and triamterene on urinary K+ excretion.
• Glucagon and insulin on blood sugar level.

4. Receptor antagonism: The antagonist binds to the same receptor as the agonist and
inhibits its effects. It can be competitive or noncompetitive.

a. Competitive antagonism (equilibrium type): In competitive antagonism, both

agonist and the antagonist bind reversibly to same site on the receptor.

b. Noncompetitive antagonism: The antagonist binds to a different site on the

receptor and prevents the agonist from interacting with the receptor. In this type,
the antagonistic effect cannot be overcome by increasing the concentra- tion of the
agonist.
e.g. diazepam and bicuculline.
22a. Main antidotes, their use for treatment of various types of toxicity.
Antidotes are drugs specifically interacting with some poisons. They act either by the
preventing of absorption or by inactivating or antagonizing the action of the
poisons.

Main antitodes and their treatment:

ANTIDOTE Poisoning

Acetycysteine Acetaminophen

Atropine + pralidoxime (for irreversible AChE inhibitors—physostigmine,

AChE inhibitors) neostigmine, and pyridostigmine;
organophosphates, including insecticides,
such as malathion and parathion

Deferoxamine iron

Digoxin immune F(ab) Digoxin

Dimercaprol (BAL) Arsenic, gold, mercury, lead; oral succimer

for milder lead and mercury toxicity

EDTA Backup in lead poisoning, then for rarer

toxicities (Cd, Cr, Co, Mn, Zn)

Esmolol Theophylline, beta agonists

Ethanol, fomepizole Methanol or ethylene glycol

Flumazenil Benzodiazepines, zolpidem, zaleplon

Naloxone Opioid analgesics

Oxygen Carbon monoxide

Penicillamine Copper (e.g., Wilson’s disease), iron, lead,

mercury

Physostigmine Anticholinergics: atropine, antihistamine,

antiparkinsonian—not tricyclics

Protamine Heparins

Vitamin K Warfarin and coumarin anticoagulants

 Activated charcoal Nonspecific: all oral poisonings except Fe,
CN, Li, solvents, mineral acids, or corrosives

Unithiol Mercury,lead,cardiac glycoside

Potassium permanganate poison with morphine, some alkaloids and

phosphor.

CLASSIFICATION OF ANTIDOTES

1) Sulfur containing compounds

– Dimercaprol (Unithiol)

– Sodium thiosulfate

– N-Acetylcysteine

2) Chelating agents

– Sodium edeteate (trilon B, EDTA–Natrium)

– Tetacin-calcium (Calcium-EDTA)

– Deferoxamine (desferral)

– Penicillamine

3) Cholinesterase reactivators

– Pralidoxim (PAM)

– Alloxim

– Dipiroxim

– Isonitrosine

4) Antagonists of opioids

– Naloxone

– Naltrexone

5) M-cholinoblockers – Atropine sulfate

6) Anticholinesterases – Neostigmine (Proserin)

7) Preparations of other groups

– Cromosmonum (Methyleni coeruleum)

– Ethanol (Spiritus aethylicus)

– Potassium permanganate ;Activated charcoal (Carbo activatus)

MECHANISM OF ACTION OF ANTIDOTES

-binding to receptors (e.g., atropine, naloxone)

-acting on enzymes (e.g., cholinesterase reactivators)

-displacement from tissue binding sites (e.g., ethanol under the conditions of poisoning with methanol)

-exchanging with poison, binding to poison (e.g., chelating agents)

-the replenishment of depleted essential substances (sulfur containing agents).

23a. Pharmacovigilence, principles and methods of its implementation.

Also known as drug safety, is the pharmacological science relating to the collection,
detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical
products.
 Principles:
- What are adverse drug reactions (ADR)and adverse drugs events (AE)?
- Difference b/w ADR & AE
- Serious and NON-serious ADR
- Valid and NON-valid ADR
- Unlisted and Listed ADR
- Workflow in pharmacovigilance for ADR.

 Methods of its implementation:

- Detection of unsafe medical preparation
- Detection of risk groups of pharmacotherapy
- Detection of typical medical errors being the reason for ADR & working out
measures for their minimization.
- Education healthcare professionals, for medical preparation consumers about
safety issues of its usage.
- Implementation of monitoring in hospitals as optimal procedure for collecting
information about ADR.
- Involvement of nurses, pharmacists, in ADR reporting

24a. Negative side effects of medical agents of allergic nature.

Negative side effects of medical agents of allergic nature are :-
1. Type I hypersensitivity (immediate type, anaphylactic) reactions It is a rapidly occurring
reaction, hence called immediate hypersensitivity reaction. The manifestations are itching,
urticaria, hay fever, asthma or even anaphylactic shock. Itching, rhinitis and urticaria are
treated with antihistamines.
Anaphylactic shock is a medical emergency and should be treated with:
1. Inj. adrenaline (1:1000) 0.3-0.5 mL intramuscularly.
2. Inj. hydrocortisone 100-200 mg intravenously.
3. Inj. pheniramine 45 mg intramuscularly/intravenously.
4. Maintenance of patient airway, intravenous fluids.
2. Type II hypersensitivity (cytotoxic) reactions: The antibodies (IgG and IgM) react with
cell-bound antigen and cause activation of complement, which destroys the cells.

3. Type III hypersensitivity (Arthus, serum sickness) reactions In this type of

reaction,antibodies involved are mainly IgG.
AG: AB complexes are formed Fix complement then Deposition of complexes on vascular endothelium-→ Destructive
inflammatory response.

For example, serum sickness (fever, urticaria, joint pain, lymphadenopathy) with penicillins
and sulphonamides; acute interstitial nephritis with nonsteroidal anti-inflammatory drugs
(NSAIDS) and Stevens-Johnson syndrome with sulphonamides.

4. Type IV hypersensitivity (cell-mediated or delayed hypersensitivity) reactions It is

mediated by sensitized T lymphocytes. Reexposure to the antigen leads to a local
inflammatory response. The manifestations usually occur 1-2 days after exposure to the
sensitizing antigen.

Common allergy-causing drugs include:

Anticonvulsants (diazepam), Insulin (especially animal sources of insulin), Iodinated.

(containing iodine) x-ray contrast dyes (these can cause allergy-like reactions), Penicillin and
related antibiotics (streptomycin, chloroquine), Sulfa drugs (sulfadiazine), some diabetes
medications, such as glyburide can cause allergies.

25a. Negative side effects of medical agents of non-allergic nature.

Side effect may be based on the same action as the therapeutic effect, e.g., atropine is
used in pre-anesthetic medication for its anti-secretory action. The same action produces
dryness of mouth as a side effect.
Acetazolamide (carbonic anhydrase inhibitors) acts as a diuretic by promoting bicarbonate
excretion acidosis occurs as a side effect due to bicarbonate loss.
Side effect may also be based on a different facet of action, e.g., promethazine produces
sedation which is unrelated to its anti-allergic action; estrogens cause nausea which is
unrelated to their anti-ovulatory action. An effect may be therapeutic in one context but
side effect in another context, e.g., codeine used for cough produces constipation as a side
effect but is it's a therapeutic effect in traveler’s diarrhea; depression of A-V conduction is
the desired effect of digoxin in atrial fibrillation.
Sulfonamides used as antibacterial were found to produce hypoglycemia and acidosis as
side effects which directed research resulting in the development of hypoglycemic
sulfonylureas and carbonic anhydrase inhibitor-acetazolamide.
 26a. Toxic action of medical agents.
These are the result of excessive pharmacological action of the drug due to overdosage or
prolonged use.
Overdosage may be absolute(accidental, homicidal, suicidal) or relative(i.e., usual dose of
gentamicin in presence of renal failure).
They result from functional alteration (high dose of atropine causing delirium) or drug
induced tissue damage (hepatic necrosis from paracetamol overdosage).
The CNS, CVS (cardiovascular), kidney, liver, lung, skin and blood forming organs are most commonly involved in drug
toxicity. e.g. ototoxicity, neurotoxicity, and nephrotoxicity of streptomycin.

Phototoxic Drug or its metabolite accumulates, phototoxicity: in the skin, absorbs light and
undergoes a photochemical reaction followed by a photobiological reaction resulting in
local tissue damage (sunburn-like), i.e. erythema, edema, blistering which have fast onset
and shorter duration after exposure ends.

Toxicity may result from extension of the therapeutic effect itself, e.g. coma by barbiturates,
complete A-V block by digoxin, bleeding due to heparin. Another action may be responsible for
toxicity.

EXAMPLE-

 Morphine (analgesic) causes respiratory failure in overdosage,

 Imipramine (antidepressant) overdose causes cardiac arrhythmia,
 Streptomycin (antitubercular) causes vestibular damage on prolonged use.


27a. Embriotoxic, fetotoxic, teratogenic action of drugs and poisons.

EMBRYOTOXICITY: Week 1 to Week 8

Adverse effects on the embryo due to a substance that enters the maternal system and
crosses the placental barrier; the effects of the substance may be expressed as embryonic
death or abnormal development of one or more body systems, and can be deleterious/
harmful to maternal health.

Example--maternal alcoholism, anticonvulsants, neurotropic-anorectic drugs, oral

anticoagulants (warfarin), alkylating agents, and oral hypoglycemic); female sex hormones,
tranquilizers, salicylates (aspirin), antibiotics, antituberculosis drugs, quinine and other
antimalarial, anesthetics, insulin, and lithium carbonate

FETOTOXICITY: Week 9 to week 37 Adverse fetal effects due to toxins entering the
maternal circulation and crossing the placental barrier, which may compromise maternal
health and appear as fetal malformations, altered growth and in utero death.

Fetotoxic drugs Clomipramine; Neonatal lethargy, hypotonia, cyanosis, hypothermia

Cyclophosphamide; Various congenital malformation Mobius sequence, cramping
abdominal pain, and stimulate uterine contraction may induce abortion; peptic ulcer.
 Penicillamine: Cutis laxa [loose skin], other congenital malformations; Warfarin: hypoplastic
nasal bridge, chondrodysplasia; CNS malformations; Risk of bleeding. Discontinue use one
month before delivery.

TERATOGENIC ACTION: Teratogenic actions are caused by teratogens; they are substances
that may cause birth defects through a toxic effect on an embryo or fetus. Known
teratogens include: thalidomide, mercury, alcohol, lead, and polychlorinated biphenyls
(PCBs).

Teratogens and the effects they cause:

-Thalidomide: phocomelia, multiple defects of internal organs.

- Anticancer drugs (methotrexate): cleft palate, hydrocephalus, multiple defects, fetal

death.

- Androgens: virilization; limb, esophageal, cardiac defects

- Progestin: virilization (- Thalidomide: phocomelia, multiple defects of internal organs -
Anticancer drugs (methotrexate): cleft palate, hydrocephalus, multiple defects, fetal death
- Androgens: virilization, limb, esophageal, cardiac defects

- Progestin: virilization (is a condition in which women develop male-pattern hair growth
and other masculine physical traits) of female fetus

- Tetracycline: discolored and deformed teeth, retarded bone growth

- Warfarin: depressed nose, eye and hand defects, growth retardation

- Phenytoin: hypoplastic phalanges, cleft/lip palate, microcephaly

- Phenobarbitone: various malformations

- Carbamazepine: neural tube defects, other abnormalities

- Valproate sodium: Spina bifida and other neural tube defects and limb abnormalities

- Alcohol: low IQ baby, growth retardation, fetal alcohol syndrome

- ACE inhibitors: hypoplasia of organs, growth retardation, fetal loss

Indomethacin/aspirin: premature closure of ductus arteriosus.

28a. Significance of genetic factors in development of negative effects of medical agents.

The study of relation between genetic factors and drug response is known as
Pharmacogenetics.
-All key determinants of drug response which include transporters, metabolizing enzyme,
ion channel, receptor with their coupler and effectors are controlled genetically.
Pharmacogenomic is the use of genetic information to guide the choice of drug and dose on
an individual basis.
It is intended to indentify individual who are either more likely or less likely to respond to a
drug, as well as those who required altered dose of certain drug
There are genetic factors like:--
Genetic polymorphism
-Is the existence in a population of two or more phenotype with respect to the effect
of drug.
Idiosyncrasy abnormal drug reaction due to genetic disorder like
-Acetylation
-oxidation
-Succinyl choline apnea
-Glucose 6-phosphate dehydrogenase deficiency

Polymorphism of N-acetyl transferase 2 gene results in rapid and slow acetylator status
-Slow acetylator phenotype
– isoniazid peripheral
- Rapid acetylator phenotype
–hepatitis

Pseudocholinesterase deficiency succinyl choline (Sk. Muscle relaxant)

Succinylcholine apnea due to paralysis of respiratory muscle Can be malignant
hyperthermia, abnormal calcium release by sarcoplasmic reticulum, muscle spasm,
increase in temperature
Deficiency of glucose-6 phosphate dehydrogenase
- In RBC is responsible for hemolytic anemia upon exposure to some oxidizing drugs;-
like antimicrobial drugs primaquine.

29a. Patient factors affecting drug action.

 Age: as we age, total body water and muscle mass decrease while percentage of body
fat increases. These changes can lead to drugs having a longer duration of action and
increased effect. Drugs that were effective may become compounded and
overexceed their therapeutic threshhold causing increased side effects.

 Weight: In patients with extra body weight, the drugs may not get to those optimal
levels, as there is more body mass for the drug to saturate,

 Gender: women are prone to torsades de pointes, medications known to prolong the
QT interval should be used with caution. Women should receive lower dosages of
digoxin and have lower serum concentration targets than men because of higher
mortality rates.
  psychological state: efficacy of drugs can be affected by patient’s belief, attitude and
expectations; particularly CNS drugs (more GA in nervous and anxious patients.)
Placebo- substance or treatment which is designed to have no therapeutic
value. Common placebos include inert tablets (like sugar pills), inert injections
(like saline)

 Diseases: influence drug disposition e.g. GI diseases (in coeliac diseases, amoxicillin
absorption is decreased, while cotrimoxazole & cephalexin is increased.).
liver diseases (e.g. cirrhosis. Increased dug bioavailability with high first pass
metabolism,also metabolism and elimination of the drug may be reduced.)

 genetic factors.

30a. Cholinergic synapse, its chemical structure and function. Main effects of
acetylcholine. Cholinereceptors, its localization. Classification of medical agents that affect
choline receptors.
The nerve endings of postganglionic parasympathetic nerves release a neuro-transmitter
acetylcholine, such synapses (neural junction) are named cholinergic synapses.
Chemical structure - Each synapse contains a presynaptic membrane, a synaptic gap (cleft),
and a post- synaptic membrane with cholinergic receptors.

Function :- Acetylcholine is synthesized in the presynaptic part of the nerve ending. It is

deposited in vesicles, releases into the synaptic gap, and interacts with cholinoreceptors on
the postsynaptic membrane.

Main effects of acetylcholine :-

Muscarinic Actions
I. Cardiovascular system
(a) Heart: heart rate is reduced
(b) Blood vessels: vasodilatation and a fall in blood pressure (BP)
2. Smooth muscles
(a) Gastrointestinal tract (b) Urinary bladder (c) Bronchi.
3. Exocrine glands: Increase in salivary, lacrimal, sweat, bronchial, gastric and other
gastrointestinal (GI) secretions. .

Eye :- ACh does not produce any effect on topical administration because of its poor
penetration through tissues.

Nicotinic Actions.
1. Autonomic ganglia: Higher doses of ACh produce dangerous muscarinic effects especially
on the heart. Higher doses of ACh stimulate both sympathetic and parasympathetic ganglia
causing tachycardia and rise in BP.
2. Skeletal muscles: At high concentration, ACh initially produces twitching, fasciculations
followed by prolonged depolarization of NMJ and paralysis.
 3. Actions on CNS: Intravenously administered ACh does not cause any central effects
because of its poor penetration through the blood-brain barrier (BBB).

There are two types of cholinergic receptors:

– M-cholinoreceptors (muscarinic) with subtypes M1, M2, M3, M4, M5
Locations: CNS, Eye, Heart, Blood vessels, Bronchi (smooth muscles, glands) Gut
(smooth muscles, glands) Urinary bladder
– N-cholinoreceptors (muscarinic) with neuronal and muscular subtypes.
Location: CNS, Adrenal medulla, Carotid glomerulus, Sympathetic and
parasympathetic ganglia, Skeletal muscles, Uterus, Sweat glands

CLASIFFICATION

Cholinergic drugs are preparations acting on cholinergic neurotransmission. They are

divided into cholinergic agonists, and cholinergic antagonists.

A. Cholinoblockers
 M-cholinoblockers:
Non-selective
Natural agents: Atropine sulfate, Hyoscine (Scopolamine hydrobromide),
Platyphylline hydrotartrate, Belldoonna dry extract,Synthetic.

semisynthetic agents: Butylscopolamine (buscopan), Prifinium bromide

(riabal), Ipratropium bromide (Atrovent), Tropicamide.

Selective: Pirenzepine (Gastrocepine), darifenacin, methoctramine.

 N-cholinoblockers
A) Ganglion blockers:

-Quaternary amines: Hexamethonium (benzohexonium), Hygronium,

pentaminum
-Tertiary amines: Pachycarpine hydroiodide, Pirilenum

B) Myorelaxants
-Non-depolarizing agents: d-tubocurarine chloride, pancuronium bromide,
pipecuronium bromide, mellictinum
- Depolarizing agents: Succinylcholine (dithylinum)

B. Cholinomimetics:
-M-, N- cholinomimetics
 -Direct acting: acetylcholine, Carbacholin
-Indirect acting(anticholinesterase): Neostigmine (proserin), Physostigmine,
pyridostigmine, galanthamine hydrobromide, isoflurophate, phosphacolum,
arminum.
-M-cholinomimetics: Pilocarpine hydrochloride, Aceclidinum
-N-cholinomimetics: Cytitonum, lobeline hydrochloride.

31a. Localization of M-cholinergic receptors. Сlassification of medical agents acting on M

cholinergicreceptors.
Muscarinic receptors: Is a G-coupled protein receptor that recognize muscarine.
There are five types of muscarinic receptors namely M1, M2, M3, M4, M5. These receptors
are found on ganglia of the peripheral nervous system and on the autonomic effector
organs, such as the heart, smooth muscle, brain, and exocrine glands (Gut (smooth muscles,
glands), Urinary bladder, Uterus, eye, CNS, heart, blood vessels, bronchi (smooth muscles,
glands), sweat gland.
All five subtypes are found on neurons, M1 receptors are also found on gastric parietal cells,
M2 receptors on cardiac cells and smooth muscle, and M3 receptors on the bladder,
exocrine glands, and smooth muscles.
Two groups of drugs—M-cholinomimetic (muscarinic) and M-cholinoblockers
M-,N-cholinomimetics

 Direct-acting: Acetylcholine, Carbachol (Carbocholinum)

 Indirect-acting (anticholinesterases): Neostigmine (Proserinum),
Physostigmine, Galanthamine hydrobromide, Isoflurophate
 M-cholinomimetics: Pilocarpine hydrochloride, Aceclidine

Carbachol (Carbacholinum) has the chemical structure similar to acetylcholine, but is not destroyed by cholinesterases; is
direct acting M-, Ncholinomimetic with the prevalence of M-cholinergic activity; now is applied topically for the treatment
of glaucoma (eye drops).

Pilocarpine is an alkaloid from Pilocarpus pinnatifolius, is a M-cholinomimetic; has strong systemic M -cholinomimetic
activity, but is toxic; nowadays is used only for the treatment of glaucoma (eye drops, eye ointment, or eye membranes),
seldom is used in xerostomia.

Aceclidinum is a synthetic preparation; is administered SC, IM, or topically (eye drops); is not toxic; does not penetrate
CNS; is M-cholinomimetic; is used for the treatment of atonia of the intestine and urinary bladder, as well as for glaucoma.

M-cholinoblockers are the drugs which block neurotransmission in the muscarinic synapses
of the parasympathetic nerves and decrease the effects of parasym-pathetic innervation.
They also block M-cholinoreceptors in sympathetic neurons innervating sweat glands.
CLASSIFICATION

A. Non-selective
1. Natural agents:
– Atropine sulfate

– Hyoscine (Scopolamine hydrobromide)

– Platyphylline hydrotartrate – Belldoonna dry extract

2. Synthetic and semisynthetic agents :

– Butylscopolamine (buscopan)

– Prifinium bromide (riabal)

– Ipratropium bromide (Atrovent)

– Tropicamide

B. Selective

– Pirenzepine (Gastrocepine), darifenacin, methoctramine, himbacine

 32a. Localization of N-cholinergic receptors. Сlassification of medical agents acting on N-
cholinergicreceptors.
Nicotinic receptors are located in the CNS, the adrenal medulla, autonomic ganglia, and the
neuromuscular junction (NMJ) in skeletal muscles.
Pharmacodynamics of cholinomimetics:

They stimulate N-cholinoreceptors in zona carotis and increase in the activity of the respiratory and vasomotor centers
resulting in the short stimulation of breathing and elevation of BP. They also stimulate N-cholinoreceptors in the adrenal
medulla, increase the secretion of epinephrine, which causes vasoconstriction and the elevation of BP

There are two groups of drugs acting on Nicotinic receptors—Cholinomimetic and

Cholinoblockers.

❖ N-cholinomimetics:-- Cytitonum, Lobeline hydrochloride.

Cytitonum

 stimulates N-cholinoreceptors;
 reflexly stimulates respiration and increases BP;
 is used for emergency help in respiratory arrest and collapse;
 is an ingredient of combined tablets against tobacco abuse.
 is administered IV, acts 3-5 min.
Lobeline Hydrochloride

 is an alkaloid;
 is administered IV and acts during 3-5 min; the mechanism of action is similar to
Cytitonum;
 is used for emergency help in the respiratory arrest, asphyxia, asphyxia of
newborns;
 is used to treat tobacco abuse in the form of combined tablets “Lobesil”;
is not used for collapse due to its ability to provoke transitory a decrease in BP resulting
from the stimulation of n.vagus center.

N-Cholinoblockers : are the drugs, which block neurotransmission in the nicotinic synapses in
ganglia or in skeletal muscles. N-cholinoblockers aredivided into:

Neuromuscular blockers (myorelaxants) and Ganglion blockers.

GANGLIONIC BLOCKERS : Ganglionic blockers are preparations which block N-cholino

recepors in ganglia.
1) Quaternary amines: Hexamethonium (Benzohexonium), Hygronium, Pentamine

2) Tertiary amines: Pachycarpne Hydroiodide, Pempidine (Pirilenum)

 MYORELAXANTS: Myorelaxants or neuromuscular blockers are cholinergic drugs which
interfere with the transmission of nervous impulses in the synapses of skeletal muscles
causing their relaxation.

1). Non-depolarizing agents: d-Tubocurarine chloride, Pancuronium bromide,

Pipecuronium bromide, Rocuronium bromide

2). Depolarizing agents: Succinylcholine (Dithylinum)

PHARMACODYNAMICS OF GANGLION BLOCKERS

- the dilation of blood vessels, redistribution of blood in the body, lowering of BP

- the dilation of bronchi

- a decrease in secretion and motility of the bowels, spasmolytic action

- a decrease in the tone of the urinary bladder and urinary pathways

- an increase in the sensitivity of myometrium to oxytocin resulting in the stimulation

of uterus contractions in the labor.

- a decrease in sweat secretion.

- changes in intraocular pressure which depends on the type of glaucoma.

33a. Adrenergic receptors, its localization. Classification of medical agents that affect
adrenergicreceptors.
There are 5 types of adrenergic receptors- alpha1, 2 and Beta-1,2,3
Drugs acting on adrenergic synapses are named adrenergic drugs. They are divided into two groups:
adrenergic agonists and adrenergic antagonists (adreno-blockers and sympatholytics)
CLASSIFICATION OF ADRENERGICS

α-, β-adrenomimetics

Direct-acting

– Adrenaline hydrochloride (Epinephrine)

 Indirect-acting

– Ephedrine hydrochloride

α-adrenomimetics

Non-selective

– Noradrenaline hydrotartrate (α1, α2 > β)

Selective

– Phenylephrine (Mesatonum) (α1)

– Naphazoline (Naphthyzinum) (α2)

– Halazolin (Xylometazoline) (α2)

β- adrenomimetics

Non-selective

– Isoprenaline (Isadrinum) (β1, β2)

Selective

– Dobutamine (β1)

– Salbutamol (Albuterol) (β2)

– Fenoterol (β2)

Anti-adrenergic drugs are preparations for a decrease in the neurotransmission in adrenergic

synapses due to blockade of adrenoceptors or due to presynaptic inhibition of norepinephine
release.

CLASSIFICATION ON ADRENERGIC ANTAGONIST

α-adrenoblockers

Non-selective

– Phentolamine hydrohloride

Selective

– Prazosin

– Doxazasin

β-adrenoblockers

Non-selective

– Propranolol (Anaprilin)

– Oxprenolol Selective

– Metoprolol – Atenolol – Nebivolol – Bisoprolol

 α-, β-adrenoblockers

– Labetalol – Carvedilol

Sympatholytics -Guanethidine (Octadinum) – Reserpine.

CROSS QUE-

PHARMACODYNAMIC OF ADRENERGIC ANTAGONIST

the dilation of peripheral blood vessels, reducing of peripheral resistance, an increase in venous capacity a decrease in BP
the improvement of trophy of peripheral tissues the stimulation of gut motility the stimulation of the salivary, lacrimal,
pancreatic, and respioratory tract secretions a decrease of urine retention in patients with prostate hyperplasia

Noradrenaline is a catecholamine; it has a non-selective action on adrenocep-tors with a preferable action on α-

adrenoceptors; has a short-durative action, is administered only by IV infusion in collapse and acute hypotension; may
cause strong vasoconstriction and the necrosis of soft tissues, if it is administered SC or IM; is contraindicated in blood loss,
cardiogenic shock, long-lasting shock.

Phenylephrine (Mesatonum) is a non-catecholamine; has a selective action on α1-adrenoceptors; may be taken orally, is
administered SC, IM, IV, or topically; has the duration of action of 4-6 hrs; is used in acute and chronic hypotension, for
prolongation of local anesthesia, for producing of midriasis, as well as for a decrease in edema of the mucous membrane in
acute rhinitis or conjunctivitis.

Naphazoline and halazolin are non-catecholamines; have a selective action on α2-adrenoceptors, are used as nasal drops
for acute rhinitis, nasal bleeding, and rhinoscopia; cause tolerance and tachyphylaxis.

Isoprenaline (Isadrinum) is a synthetic catecholamine; has a non-selective action on β1- and β2-adrenoceptpors; is
administered sublingually, by inhalation, or IV; is used in a bronchial asthma attack, heart block, some types of
cardiogenous shock.

Salbutamol is a non-catecholamine; has a selective action on β2- adrenoceptors, acts longer than isoprenaline; does not
act on the heart; is used in bronchial asthma, bronchospasm and before bronchoscopia.

Fenoterol (Partusisten) is a non-catecholamine; has a selective action on β2- adrenoceptors, acts during 4-6 hrs; does not
act on the heart; is used in bronchial asthma and in danger of pregnancy interruption.

Dobutamine has a selective action on β1-adrenoceptors; increases cardiac output; is administered by IV infusion for the
emergency treatment of acute heart insufficiency and cardiogenous shock.

34a. Termination of exposure (decontamination) of poisons. Prevention of absorption of

ingestedpoisons.
Decontamination is one of the emergency treatments of a poisoned patient.
Decontamination can begin after the patient is stabilized. Airway, breathing, and circulation
are assessed and addressed initially.
The assessment for decontamination may include flushing of the eyes with saline or tepid
water to a neutral pH for ocular exposures, rinsing of the skin for dermal exposures, as well
as administration of gastrointestinal (GI) decontamination with gastric lavage, activated
charcoal, or whole bowel irrigation (utilizing a polyethylene glycol electrolyte balanced
solution) for selected ingestions.
 Several substances do not adsorb to activated charcoal (for example, lead and other heavy metals, iron, lithium, potassium,
and alcohols), limiting the use of activated charcoal unless there are co-ingested products.
The prevention of absorption of ingested poisons:--

- Gastric lavage can limit the absorption of poison if done within 2-3hrs of
poisoning. If patient is unconscious, endotracheal intubation should be done before
gastric lavage.
- Gastric lavage is done with normal saline or other can be used like leukwarm
water, potassium paramagnet, sodium bicarbonate etc.
- Lavage should be done the fluid is clear.
- Laxatives like magnesium sulphate or citrate can be used orally to promote
elimination of the ingested poison.
- Oral polyethylene glycol electrolyte solution can be used for whole bowel
irrigation of the gastrointestinal tract in case of poisoning due to iron, lithium,
cocaine heroin, foreign bodies, etc.
To promote elimination of absorbed portion of the drugs:
(a) Diuretics (i/v. mannitol or furosemide) are used to promote the elimination of
absorbed portion of the drug. Renal elimination of some of the drugs can be
increased by altering the pH of urine, e,g. alkalinisation of urine in salicylate
poisoning and acidification of urine in amphetamine poisoning.
(b) Dialysis is used in cases of severe poisoning, eg. lithium, aspirin, methanol, etc.
Symptomatic treatment: Intravenous diazepam 5-10 mg if there are con- vulsions and
external cooling for hyperpyrexia.
Maintenance of fluid and electrolyte balance: Hyponatraemia should be treated with i.v.
normal saline and hypernatraemia with i.v. furosemide.
Hypokalaemia is treated with potassium chloride, oral or slow i.v. infusion.
Thiazides or furosemide can be used to treat mild hyper kalaemia. Severe hyperkalaemia is
treated with 10% calcium gluconate
Intravenous sodium bicarbonate is used to treat metabolic acidosis
GI disorders after poisoning: vomiting, nausea, diarrhea, constipation, a loss of appetite liver lesions: hepatic necrosis,
hepatic insufficiency renal insufficiency lesions of the skin and mucous membranes: necrosis, irritation, exfoliation, rash.

35a. Antidotes.

An antidote is a drug, chelating substance, or a chemical that counteracts (neutralizes) the

effects of another drug or a poison. Antidotes either counteract one particular drug,
whereas others (such as charcoal) may help reduce the toxicity of numerous drugs.

GENERAL MECHANISMS OF ANTIDOTE ACTION

Antidotes exert an antitoxic effect by a number of mechanisms:
-by binding to receptors (e.g. atropine, naloxone)
-by acting on enzymes (e.g. cholinesterase reactivators)
-by displacement from tissue binding sites (e.g. ethanol under the conditions of poisoning
with methanol)
-by exchanging with poison, binding to poison (e.g. chelating agents)
-by the replenishment of depleted essential substances (e.g. sulfur containing agents)

Antidotes are classified into:

1. Sulfur containing compounds: Dimercaprol (Unithiol), Sodium thiosulfate,
Acetylcysteine
2. Chelating agents: sodium edeteate (trilon B, EDTA–Natrium), Tetacin-calcium (Calcium-
EDTA), Deferoxamine (desferral), Penicillamine
3. Cholinesterase reactivators: Pralidoxim (PAM), Alloxim, Dipiroxim, Isonitrosine
4. Antagonists of opioids: Naloxone, Naltrexone
5. M-cholinoblockers : Atropine sulfate
6. Anticholinesterases: Neostigmine (Proserinum)
7. Preparations of other groups: Cromosmonum (Methyleni coeruleum), Ethanol (Spiritus
aethylicus), Potassium permanganate, Activated charcoal (Carbo activatus).
Antidote poisoining

acetylcysteine Acetaminophen

Atropine + pralidoxime (for irreversible AChE inhibitors—physostigmine,

AChE inhibitors) neostigmine, and pyridostigmine;
organophosphates, including insecticides,
such as malathion and parathion

Deferoxamine iron

Digoxin immune F(ab) Digoxin

Dimercaprol (BAL) Arsenic, gold, mercury, lead; oral succimer

for milder lead and mercury toxicity

EDTA Backup in lead poisoning, then for rarer

toxicities (Cd, Cr, Co, Mn, Zn)

Esmolol Theophylline, beta agonists

Ethanol, fomepizole Methanol or ethylene glycol

Flumazenil Benzodiazepines, zolpidem, zaleplon

Naloxone Opioid analgesics

Oxygen Carbon monoxide

Penicillamine Copper (e.g., Wilson’s disease), iron, lead,

mercury

Physostigmine Anticholinergics: atropine, antihistamine,

antiparkinsonian—not tricyclics

Protamine Heparins

Vitamin K Warfarin and coumarin anticoagulants

Activated charcoal Nonspecific: all oral poisonings except Fe,

CN, Li, solvents, mineral acids, or corrosives

Unithiol Mercury,lead,cardiac glycoside

Potassium permanganate poison with morphine, some alkaloids and

phosphor.
Radioprotectors are used as antidotes against radiation, they are compounds that are
designed to reduce the damage in normal tissues caused by radiation.
Examples of radioprotectors are compounds containing sulfhydryl (thiol) groups (-SH), such
as cysteine, mercaptoamines and indolylalkylamines.
Other agents called mitigators, can be used to reduce the toxicity even after radiation has
been delivered.

36a. Enhancement of poisons elimination.

Elimination is one of the ways of removing toxic substances from the body. Elimination of
poisons is enhanced by three mechanism which are: multiple-dose activated charcoal use,
hemodialysis and urinary alkalinization.

1. Multiple-dose activated charcoal therapy: enhances the elimination of certain drugs

by creating a gradient across the lumen of the gut.
Drugs like theophylline, phenobarbital, digoxin, carbamazepine, and valproic acid can be
eliminated by charcoal.
Medications move from areas of high concentration to low concentration, so the drug that
is already absorbed can cross back into the gut and adsorbed by the activated charcoal.
Also, activated charcoal blocks the reabsorption of drugs that undergo enterohepatic re-
circulation (such as phenytoin), by adsorbing the substance to the activated charcoal.
Bowel sounds must be present before each activated charcoal dose to ensure movement
of the GI tract and prevent obstruction.

2. Hemodialysis: The removal or elimination of some medications or toxins may be

enhanced by hemodialysis if the drug has low protein binding, small volume of distribution,
small molecular weight, and water solubility of the toxin.

Methanol, ethylene glycol, salicylates, theophylline, phenobarbital, and lithium can be

eliminated.

3. Urinary alkalinization: Alkalinization of the urine enhances the removal or elimination of

salicylates or phenobarbital. Increasing the urine pH with intravenous sodium bicarbonate
transforms the drug into an ionized form that prevents reabsorption, so it can be
eliminated by the kidney.

4. Others--

 Forced diuresis with furosemide or mannitol

 The altering of urinary pH (alkalinization for acidic substances and acidification for
alkaline drugs).
 The administration of drugs stimulating enzymes activity in the liver for the
fastening of poison metabolism (e.g. phenobarbital; glucose, and vitamins in
 poisoning with ethanol)
 Analeptics for the stimulation of respiration and an increase of the excretion of
poison through the lungs (Carbogen, etimizol)
 Peritoneal dialysis, chemosorption
 The use of osmotic purgatives (magnesium sulfate, sodium sulfate)

37a. Pathogenetic (symptomatic) therapy of acute poisonings.

Symptomatic therapy (non-specific) is a therapy which helps with the supporting of
damaged functions of the organism and also helps with resuscitation (lack of breathing or
heart rate) of the patient. Symptomatic therapy is dependent on the main syndromes of
intoxications.
1). Emergency help needed for Pulmonary edema
- diuretics: furosemide (IV), mannitol (IV infusion), Urea pura /carbamide (IV infusion)

- drugs that cause redistribution of blood: ganglia blockers (hygronium, IV infusion;

pentaamine, IV, or IM); peripheral vasodilators (nitroglycerine, IV; sodium
nitroprusside, IVinfusion)
- cardiac glycosides: strophanthin (IV), corglycone (IV)
- glucocorticoids: prednisolone (IM, IV)
- narcotic analgesics: morphine hydrochloride
- surfactants: exosurf, curosurf

- oxygen with anti-foam agents (vapor of ethanol).

- α- and α,β–adrenergic agonists: phenylephrine (IM, SC, or IV),
noradrenaline -hydrotartrate (IV infusion), adrenaline hydrochloride (SC)
- analeptics: nikethamide (SC, IV), camphor (SC), sulfocamphocaine (IV, IM, Subcutaneously)

2) A seizures attack is treated by:

- anxiolytics: diazepam (IV, IM)
- neuroleptics: chlorpromazine (IV, IM)
- I/V general anesthetics: sodium oxybutyrate (IV, IM)
– magnesium salts: magnesium sulfate (IV, IM).
N-cholinergic agonists: Cytitonum (IV), lobeline hydrochloride
3) The inhibition of respiration should be treated with:

- analeptics: niketamide (IV, SC), camphor (SC), sulfocamphocaine (IV, IM, SC), bemegride
(IV), etimizol (IV), Carbogenum (carbon dioxide + oxygen, by inhalation).

4) Acute heart failure is treated by:

- cardiac glycosides from Strophanthus group: stophanthin (IV), corglycon (IV)
- non-glycoside inotropic agents: dobutamine (IV infusion).

38a. Principles of providing medical assistance in bronchial asthma attack.

Asthma attacks are either acute, or subacute in nature. It is usually Characterized by
progressive worsening of shortness of breath, cough and wheezing.

The management of bronchial asthma includes: Reducing impairment & Reducing risk.
Avoidance of asthma triggers
Treatment of allergic inflammation
Dilatation of bronchi

Drugs used are –

- Broncholytic drugs: adrenomimetics (alpha, beta adrenomimetics, beta
adrenomimetics,beta2 adrenomimetics, Beta adrenomimetics such as salbutamol,
Ventolin,

- Methylxanthines such as theophylline of prolonged action

- M cholinoblockers such as atropine sulphate, ipratropil-bromidum, Ipratropium &

tiotropium (DOC in bronchospasm ) in COPD patients, and also safer in cardiovascular
disease patients.

- Mast cell stabilizers such as ketotifen

- The use of antiallergic and drugs that reduce airway hyperresponsiveness

- The use of expectorants

- Inhaled corticosteroids such as Beclomethasone, Budesonide, Dexamethasone,

Flunisolide,Fluticasone, Triamcinolone). {DRUGS OF FIRST CHOICE with any degree of
persistent asthma}
Administration of corticosteroids by inhalation limits the systemic adverse
reactions associated with oral or parenteral therapy

- The use of leukotriene inhibitors such as zileuton attract cellular infiltrates producing
epithelial injury and also increases airway in smooth muscle responsive-ness and airway
obstruction

- Cromolyn and nedocromil mast cell stabilizers decrease bronchial hyperactivity.

CLASSIFICATION

A. Bronchodilators
(i) Sympathomimetics: Salbutamol, Terbutaline, Bambuterol, Salmeterol, Formoterol, Ephedrine.
(ii) Methylxanthines: Theophylline (anhydrous), Aminophylline, Choline theophyllinate, Hydroxyethyl
theophylline, Theophylline ethanolate of piperazine, Doxophylline.
(iii) Anticholinergics: Ipratropium bromide, Tiotropium bromide.
B. Leukotriene antagonists: Montelukast, Zafirlukast.
C. Mast cell stabilizers: Sodium cromoglycate, Ketotifen. IV.
D. Corticosteroids
i. Systemic: Hydrocortisone, Prednisolone and others.
ii. Inhalational: Beclomethasone dipropionate, Budesonide, Fluticasone propionate, Flunisolide, Ciclesonide.
E. Anti-IgE antibody: Omalizumab Emergency aid:

1. Sit the person upright.

2. Give four puffs of blue reliever puffer (inhaler). Make sure you shake the puffer, put one puff into a spacer (holding
spacer) at a time and get the person to take four breaths of each puff through the spacer.
Remember: shake, one puff, four breaths. If you don’t have a spacer, simply give the person four puffs of
their reliever directly in to their mouth. Repeat this until the person has taken four puffs.
1. Wait four minutes. If there is no improvement, give four more separate puffs as in step 2. Remember: shake, one
puff, four breaths.

39a. Principles of providing medical assistance in hypovolemic shock.

Hypovolemic shock is a condition caused by a decrease in circulating blood volume. As a

result of fluid (or blood ) loss, the filling of the ventricle of the heart decrease and the
stroke volume decreases.
To provide assistance the first is to identify the cause. The cause could be divided into
external and internal. The external cause has to be treated first like in case of trauma that
lead to severe bleeding a\er which the appropriate medication.
The main goal is to restore blood volume, improve tissue perfusion and oxygenation.
- Carrying out oxygen therapy at clinical signs of acute respiratory failure.
- Carrying out infusion therapy. Intravenous infusion of crystalloid solutions of at least 800
ml for 10 minutes .
- Ringer-lock solution and refortan as i/v infusion
Ringer-Lock solution is a multicomponent physiological solution of sodium chloride (9 g/l), potassium chloride (0.2 g/l),
calcium chloride (0.2 g/l), sodium bicarbonate (0.2 g/l), and glucose (1 g/l).

- for analgesia: narcotic analgesics, nitrous oxide.

- For a decrease in ischemia: organic nitrates (nitroglycerine), beta-adrenoblocker
- For a decrease in arrhythmia: anti-arrhythmics (Lidocaine, amiodarone, polarizing
solution), beta - adrenoblockers
- anti-coagulants(heparin).
- Thrombolytics (streptokinase, alteplase).
- For a decrease in acute heart failure: inotropic drugs(dobutamine), vasodilator.
- Sodium chloride, sodium lactate, potassium chloride and calcium chloride may also be
given intravenously.
- In hemorrhagic shock and burns whole blood or plasma or plasma substitute like dextran
can be substituted.
 - With convulsive syndrome and agitation-diazepam 2-4ml of 0.5% solution intravenously,
Prednisolone 30-60 mg a\er 20-30 min iv.

40a. Principles of providing medical assistance in acute heart failure.

Acute heart failure(ARF) is a clinical syndrome characterized by a sudden disturbance of systemic

blood flow as a result of decreased myocardial contractility.

Principle—

1) enhancing cardiac output with inotropic drugs (cardiac glycosides),

2) decreasing preload with diuretics and angiotensin converting enzyme inhibitors and,
3) decreasing afterload with vasodilators like organic nitrates and ACE inhibitors
(benazepril).

Acute heart failure is treated by:

– cardiac glycosides from Strophanthus group: stophanthin (IV), corglycon (IV)

– non-glycoside inotropic agents: dobutamine (IV infusion).

- oxygen therapy is used to treat hypoxemia.

- Diuretics are indicated in patients with dyspnea caused by pulmonary edema.

Use of loop diuretics and thiazide diuretics to decrease preload, spinronolactone or epierenone
to block aldosterone receptors and decrease remodelling.

- Sympathomimetics such as dobutamine and dopamine.

- Calcium channel blockers (sometimes only AMLODEPINE because it causes more exacerbation)
- ACE-inhibitors to decrease production of Angiotensin 2 which is a potent vasoconstrictor

- Inotropes- digitoxin inhibition of cardiac sodium potassium ATPase results in increase intracellular
sodium .

- Vasopressors are prescribed in combination with inotropic drugs and fluid in fusion in the absence
of optimal perfusion with improved cardiac output.
- Norepinephrine should be used to increase systemic vascular resistance. To reduced
vascularresistance (septic shock), combined with dobutamine to improve hemodynamic
parameters.

- Vasodilator are most useful for patient with hypertension and should be used with extreme caution
in patients with chronic arrhythmia.

- Cardiac glycosides likes strophanthin(IV), corglycone from strophanthus group used to inhibit
the sodium group allowing calcium to move inside cells and increases the force of contraction.
41a. Principles of providing medical assistance in acute coronary syndromes (unstable
angina; myocardial infarction).

unstable angina is coronary heart disease caused by a buildup of plaque along the walls of
your arteries.
Myocardial infarction is the formation of the area of necrosis in the myocardium due to
local ischemia resulting from the obstruction of blood vessel, most commonly by thrombus
or embolus.
It manifests by persistent intense cardiac pain, diaphoresis, pallor, hypotension, faintness,
nausea, vomiting.

Treatment:
1. Pain, anxiety and apprehension
- glyceryl trinitrate (GTN)
- opioid analgesic (morphine/pethidine) or diazepam is administered parenterally.
DOSE: GTN- oral(2.5-ti.5mg TDS); IV(10mcg/min); sublingual tablet (0.3-0.4mg every 5min of 3 doses)

Analgin is indicated in combination with an anti-histamines and neuroleptics for residual

pain .

2. Maintenance of blood volume, tissue perfusion and microcirculation Slow IV infusion of

saline/low molecular weight dextran (avoid volume overload).
3. Correction of acidosis: i/v. sodium bicarbonate infusion
4. Prevention and treatment of arrhythmias Prophylactic i/v infusion of a β blocker. β blockers
used early in evolving MI can reduce the infarct size (myocardial salvage) and subsequent complications.

Tachyarrhythmias may be treated with i/v lidocaine, procainamide or amiodarone,

ranolazine
Bradycardia and heart block may be managed with atropine.
Calcium channel blockers. Nifedipine is important for vasospastic angina
(prinzmetal/unstable angina) (verapamil,diazepam, amlodipine).

5. Pump failure the objective is to increase cardiac output and or decrease filling pressure
without increasing cardiac work or lowering BP.
Drugs:
(a) Furosemide: indicated if pulmonary wedge pressure is > 20 mm Hg. It decreases
cardiac preload.
DOSE: Furosemide- Oral(20-80mg OD; maxti00mg/day); I.V (20-40mg for 1-2min, max200mg/dose); IM (20-
40mgfor 2hr, max200mg/dose)

(b) Vasodilators: Drugs like GTN (i/v), or nitroprusside have been mainly used.
(c) Inotropic agents: dopamine or dobutamine i.v. infusion
6. Prevention of thrombus extension, embolism, venous thrombosis
Aspirin (162–325 mg) should be given for chewing and swallowing.
This is continued at 80–160 mg/day.
Anticoagulants heparin, (followed by oral anticoagulants) enoxaparin are used primarily to
prevent deep vein thrombosis and pulmonary/ systemic arterial embolism.
Eptifibatide (anti-platelet) - DOSE: 180 μg/kg i.v. bolus, followed by 2 μg/kg/ min infusion up to 72 hours

7. Thrombolysis and reperfusion

Fibrinolytic agents, i.e. plasminogen activators—streptokinase/ urokinase/alteplase.
DOSE: Streptokinase- initial, 20,000units followed by 2000-4000units/min for 1-2hr.

8. Prevention of future attacks

(a) Platelet inhibitors—aspirin or clopidogrel given on long-term basis are routinely
prescribed
DOSE: clopidogrel (In MI: loading dose 300mg with 75mg OD)

(b) β blockers—reduce risk of reinfarction, chronic heart failure.

9. Oxygenation: By O2 inhalation and assisted respiration.

GTN should not be administered if:

• Systolic BP is < 90 mm Hg
• Heart rate is < 50 or > 100 beats/min
• Right ventricular infarction
• Hypotension caused by nitrate limits the administration of β blockers which have more powerful
salutary effects.
• Patient has taken sildenafil in the past 24 hours.

42a. Principles of providing medical assistance in lung edema.

Pulmonary edema is a condition caused by excess fluid in the lungs. This fluid collects in the
numerous air sacs in the lungs, making it difficult to breathe.
The first treatment for pulmonary edema is supplemental oxygen by a face mask or nasal
cannula.
Pulmonary edema needs emergency help, such as: –

 diuretics: furosemide (IV), mannitol (IV infusion), Urea pura (IV infusion)
 drugs caused the redistribution of blood: ganglia blockers (hygronium, IV infusion;
 pentamine, IV, or IM);
 peripheral vasodilators (nitroglycerine, IV; sodium nitroprusside, IV infusion)
 cardiac glycosides: strophanthin (IV), corglycon (IV)
 glucocorticoids: prednisolone (IM, IV)
 narcotic analgesics: morphine hydrochloride
 surfactants: exosurf, curosurf
 oxygen with anti-foam agents (vapor of ethanol).
 α- and α,β–adrenergic agonists: phenylepiphrine (IM, SC, or IV), noradrena-line
hydrotartrate (IV infusion), adrenaline hydrochloride (SC)
 analeptics: niketamide (SC, IV), camphor (SC), sulfocamphocaine (IV, IM, SC)

43a. Principles of providing medical assistance in hypertensive emergencies.

Hypertensive emergency occurs when hypertension is severe enough to cause an organ

damage.
Therapeutic goal: To reduce the blood pressure (i.e. by 30% or to 105mm Hg diastolic BP)
within a matter of minutes to an hour & to prevent further rapid deterioration of the target
organ function.
Most commonly, sodium nitroprusside (not in patients with acute coronary insufficiency, aortic
dissection, severe preeclampsia & eclampsia and increased intracranial pressure.), labetalol (B-blocker),
or fenoldopam (D1agonist= lowers BP by arteriolar vasodilation.)
 Drugs given:
o Parenteral drugs: Nitrates (nitroprusside, nitroglycerine), Ca2+ channel blockers
(clevidipine, nicardipine ), Dopamine-1 agonist (fenoldopam), Adrenergic blocking
agent (labetalol, esmolol). Other (hydralazine, enalapril, phentolamine)
o Oral (sublingual) drugs: captopril, bisoprolol, metoprolol, clopheline

44a. Principles of providing medical assistance in hyperglycemic coma.

This coma develops due to a high blood sugar level and is characterized by unconsciousness,
hyperemia of the skin, a low tone of skeletal muscles and eyes, hyperglycemia and
ketoacidosis.
Emergency help: –
-regular insulin (IV)
– 0,9% solution of sodium chloride for a decrease in hyperosmolarity of blood (IV infusion)
– 4% solution of sodium bicarbonate for the decrease in acidosis (IV infusion)
– thiamine as synergist of insulin (bigger dose).

45a. Principles of providing medical assistance in hypoglycemic coma.

Insulin (hypoglycemic) coma, can occur in diabetes when injected large dose of insulin or by
missing ameal after injection or by performing high exercise.
The symptoms
—sweating, anxiety, palpitation, tremor

—dizziness, headache, behavioral changes, visual disturbances, hunger, fatigue, weakness,

muscular incoordination and sometimes fall in BP.
Emergency help: Glucose must be given orally or i.v. (for severe cases)—reverses the
symptoms rapidly. Glucagon 0.5–1 mg i/v or Adrenaline 0.2 mg s/c.
– sweet tea and white bread by mouth during pre-coma

– 40% solution of glucose (IV) in a comatous condition

– epinephrine, prednisolone/glucagon as contra-insular hormones.

46a. Principles of treatment of anaphylactic shock.

Ans:- Anaphylactic shock (Anaphylaxis is a serious allergic reaction that is rapid in onset
and may cause death)

Principle of Treatment :-
First can we put the patient in reclining position, administer oxygen at highflow rate
and perform cardiopulmonary resuscitation if it is required.
 Inject adrenaline (IM)
repeat every 5-10 min in case patient does not improve or improvement is transient.
This is the only life saving measure.
Adrenaline should not be injected i.v. unless shock is immediately life
threatening.
 We can Administer a first generation H1, antihistamine
(pheniramine or chlorpheniramine) i.m./slow i.v.

 Intravenous glucocorticoid (hydrocortisone sod. Succinate) should be added in

severe / recurrent cases. It acts slowly, specially valuable for prolonged reactions
and in asthmatics and may be followed by oral prednisolone for 3 days.
 Adrenaline followed by short course of glucocorticoids for
bronchospasm with drug hypersensitivity.

 Glucocorticoids are the only drug effective in type I, type II, type III, typeIV.

It can be ADDED -
H1 blockers (diprazin, dimedrol, suprastin)
Mitotropic agents (euphylline)
Analeptics (cordiamine)
Bronchodilators-albuterol
Glucagon for patients taking beta blockers and with refractory hypotension.
47a. Principles of providing medical assistance in seizure and epileptic status.
Principles of the treatment of epilepsy:
-The choice of the drug according to the type of epilepsy
-A long-term treatment
-The oral administration of drugs
-An equal dose of a new drug, if the change of preparation is needed.

-Slow cancellation of the drug, to prevent a withdrawal syndrome

Anti-seizure drugs:
1. Barbiturate: Phenobarbitone
Dose of ti0 mg 1–3 times a day in adults; in children (3–5 mg/ kg/day)

2. Deoxybarbiturate: Primidone
Dose: 250–500 mg BD, children 10–20 mg/kg/day

3. Hydantoin: Phenytoin, Fosphenytoin

Dose: 100 mg BD, maximum 400 mg/day; Children: 5–8 mg/kg/day.

4. Carbamazepine, Oxcarbazepine
Dose: 200–400 mg TDS; Children 15–30 mg/kg/day.

5. Succinimide Ethosuximide
Dose: 20–30 mg/kg/day

ti. Valproic acid acid (sodium valproate) Divalproex

Dose: Adults—start with 200 mg TDS, maximum 800 mg TDS; children—15–30 mg/kg/day.

7. Benzodiazepines: Clonazepam Diazepam Lorazepam Clobazam

Dose: start with 10–20 mg at bedtime, can be increased upto ti0 mg/day

8. Phenyl triazine, Lamotrigine

9. Gabapentin analogues Pregabalin
Dose: Start with 300 mg OD, increase to 300–ti00 mg TDS as required;

10. Newer drugs Topiramate Zonisamide Levetiracetam Vigabatrin Tiagabine Lacosamide

Status epilepticus-- When seizure activity occurs for >30 min, or two or more seizures occur without
recovery of consciousness, the condition is called status epilepticus.

Treatment:

• Lorazepam: 4 mg (0.1 mg/kg in children) injected i.v. at the rate of 2 mg/min, repeated once after
10 min if required, is the first choice drug.

• Diazepam 10 mg (0.2–0.3 mg/kg) injected i.v. at 2 mg/min, repeated once after 10 min if required,
has been the standard therapy till recently. It is also more damaging to the injected vein.

• Fosphenytoin 100–150 mg/min i.v. infusion to a maximum of 1000 mg (15–20 mg/kg) under
continuous ECG monitoring is a slower acting drug which should be given if the seizures recur.

• Phenytoin sodium It should be used only when fosphenytoin is not available, because it can be
injected only at the rate of 25–50 mg/ min and causes more marked local vascular complications.

• Phenobarbitone sodium: 50–100 mg/min i.v. injection (maximum of 10 mg/kg), slower acting drug
which can be used as alternative to fosphenytoin.

• Refractory cases who fail to respond to lorazepam and fosphenytoin within 40 min of seizure onset
may be treated with i.v. midazolam/propofol/thiopentone anaesthesia.

 Severe cases of status epilepticus, who are not controlled by diazepam or other drugs, may
be paralysed by a neuromuscular blocker (repeated doses of a competitive blocker) and
maintained on intermittent positive pressure respiration till the disease subsides.

• General measures, including maintenance of airway (intubation if required), oxygenation, fluid and
electrolyte balance, BP, normal cardiac rhythm, euglycemia(normal blood glucose) and care of the
unconscious must be taken

48a. Principles of providing medical assistance in acute poisoning with organophosphorus

substances.
Organophosphorus compounds are a broad group of chemicals, including insecticides and
nerve gases (soman, sarin, tabun, and VX). Poisoning of organophosphate substances occurs
through inhalation, food poisoning and contact with skin.

Signs: hypersalivation, nausea, vomiting, spasm of the bronchi, then edema of lungs,
convulsions, unconsciousness.
Emergency help: Reactivators of cholinesterase (dipyroxime, alloxim, isonitrosine),
IM Atropine.
General measures:-
1. Remove the contaminated clothes; wash skin with soap and water. Fresh air should be
inhaled.
2. Gastric lavage should be continued till the returning fluid is clear .
3. Airway should be maintained.
4. Artificial respiration is given, if necessary
5. Diazepam should be used cautiously by slow i.v. Injection to control convulsions.

Specific measures:-
1. Atropine:
- Atropine is the first drug to be given in OP poisoning.
- Inject atropine i.v. stat and it should be repeated every 5-10 minutes doubling the
dose, if required, till the patient is fully atropinized (fully dilated, nonreactive pupils,
tachycardia, etc.).
- Atropine should be continued for 7-10 days.
- Atropine competitively blocks the muscarinic effects of OP compounds (competitive
antagonism).

2. Oximes:
- Atropine is not effective for reversal of neuromuscular paralysis.
- Neuro- muscular transmission can be improved by giving cholinesterase reactivators
such as pralidoxime and obidoxime.
- DOSE: is injected i.v. slowly in a dose of 1–2 g (children 20–40 mg/kg). Another
regimen is 30 mg/kg i.v. loading dose, followed by 8–10 mg/kg/hour continuous
infusion till recovery

OP compounds inactivate cholinesterases by phosphorylating esteratic site of the enzyme.

Oximes bind with high affinity to anionic site, react with phosphorus atom of the OP
compound, dephosphorylate the enzyme, and reactivate it.
Early administration of oximes is necessary before the phosphorylated enzyme under- goes
'aging' (loses alkyl groups) and becomes resistant to reactivation.

Chronic organophosphate poisoning

- Repeated exposure to certain fluorine containing and triaryl organophosphates results in polyneuritis and
demyelination after a latent period of days to weeks.
- Sensory disturbances occur first followed by muscle weakness, tenderness and depressed tendon reflexes—
lower motor neuron paralysis. In the second phase, spasticity and upper motor neuron paralysis gradually
supervenes.
- Recovery may take years.
- The mechanism of this toxicity is not known, but it is not due to inhibition of ChE; there is no specific treatment.

49a. Principles of providing medical assistance in acute poisoning with atropine-like

substances.
Atropine is a medication used to treat certain types of nerve agent and pesticide poisonings
as well as some types of slow heart rate, and to decrease saliva. One can get poisoned with
atropine-like substance when its overdosed.
Signs:
–– restlessness, disorientation, hallucinations, delirium, coma
–– mydriasis (dilation of pupils), absence of pupils’ reaction to the light
–– dryness of the skin and mucous membranes
 –– dysphagia (disorder in eating)
–– retention of urine
–– hyperemia of the skin elevated body temperature
Atropine may cause dry mouth, blurred vision, “sandy eyes,” tachycardia, urinary
retention, and constipation.
Emergency help:
–– neostigmine , physostigmine or galantamine other anticholinesterases (as an antidote) -
Anticholinesterases bind to acetylcholinesterase in the synaptic gap, inhibit it and decrease
acetylcholine destruction. but it should used cautiously by slow i.v. injection as it may cause
bradycardia.
The result is the accumulation of the acetylcholine amount in the synaptic gap and an
increase in acetylcholine interaction with M- and N-cholinoreceptors

–– chlorpromazine (neuroleptic-to decrease psychotic disorders)

–– barbiturates (to decrease seizures).

First aid:
A) Stabilization of the vital functions.
B) Definitive care with the poisoning including: identification of the poison, prevention
of further absorption, antidotes, enhancement of elimination, and treatment of
complications.

50a. Principles of providing medical assistance in acute poisoning with narcotic substances.
Narcotic is referred to as any psychoactive compound with sleep-inducing properties,
and euphoric properties. Examples of opioids are morphine, codeine, oxycodone,
oxycodone + acetaminophen, and hydrocodone + acetaminophen.
The signs and symptoms of an opioid overdose emergency can include:

● Sever respiratory depression may cause death

● Unusual sleepiness or unresponsiveness, Breathing will be slow or absent (Cheyne stocks breathing)

● Slow heartbeat or low blood pressure, Skin feels cold and clammy

● Pupils are small, Nails and lips are blue, spasm of the intestine and bowel.

Principles of treatment with narcotic poisoning like morphine.

Emergency help:
The lavage of the stomach with 0,5% solution of potassium permanganate
Naloxone, IV (an antagonist of narcotic analgesics)
Atropine (for a decrease in the vagal action of morphine).

Treatment:
 It consists of respiratory support and maintenance of BP (i.v. fluids,
vasoconstrictors).
  Gastric lavage should be done with potassium permanganate to remove unabsorbed
drug. Lavage is indicated even when morphine has been injected.
 Specific antidote: Naloxone 0.4–0.8 mg i.v. repeated every 2–3 min till respiration
picks up, is the specific antagonist of choice because it acts rapidly, does not have
any agonistic action and does not depress respiration.
 Due to short duration of action, naloxone should be repeated every 1–4 hours,
according to the response.
 Other drugs like naltrexone and nalmefene (i/v) can also be used as opioid
antagonists.

51a. Medical and social aspects of opioid addiction, principles of drug addiction treatment.
It is a chronic, relapsing brain disease that causes compulsive drug seeking and use,
despite harmful consequences to the addict and those around them & leads to changes
in the structure and function of the brain.

A person eventually feels flat, without motivation, lifeless, and/or depressed, and is unable
to enjoy things that were previously pleasurable. Now, the person needs to keep taking it
to experience even a normal happiness—which only makes the problem worse, like a
vicious cycle. Also, the person will often need to take larger amounts of the drug to
produce the familiar high—an effect known as tolerance.

Other addiction examples- barbiturates, benzodiazepine, CNS stimulant like

amphetamine andcause addiction.

Side effects of may include:

 A weakened immune system, increasing the risk of illness and infection

 Heart conditions ranging from abnormal heart rates to heart attacks and collapsed

veins and blood vessel infections from injected drugs

 Nausea and abdominal pain, which can also lead to changes in appetite and weight

loss

 Increased strain on the liver, which puts the person at risk of significant liver

damage or liver failure

 Seizures, stroke, mental confusion and brain damage

 Lung disease

 Problems with memory, attention and decision-making, which make daily living

more difficult

 Global effects of drugs on the body, such as breast development in men and
increases in body temperature, which can lead to other health problems
Physical dependence – if the patent wants to take the drug for altering general state and
mood. It is characterized by abstinence. Abstinence is a phenomenon of deprivation. Ethyl
alcohol and narcotic analgesics may cause physical dependence.
Psychological dependence – if the patient wants to take the drug for altering the mood (for
euphoria). Such kind of drug dependence is caused by psychomotor stimulants.

Social aspects of opioid addiction:

- It can also cause a person to become paranoid and untruthful about their
relationships.
- The users may even become aggressive and violent towards other people, even
their family and friends.

Principles of drug addiction treatment:

 Treatment needs to be readily available. Because drug-addicted individuals may
be uncertain about entering treatment, taking advantage of available services the
moment people are ready for treatment is critical.
 Effective treatment attends to multiple needs of the individual, not just his or her
drug abuse.
 Remaining in treatment for an adequate period of time is critical. Recovery from
drug addiction is a long-term process and frequently requires multiple episodes of
treatment.
 Behavioral therapies—including individual, family, or group counseling—are the
most commonly used forms of drug abuse treatment. involve addressing a
patient’s motivation to change, providing incentives for abstinence, building skills
to resist drug use, replacing drug-using activities with constructive and rewarding
activities, improving problem-solving skills, and facilitating better interpersonal
relationships.
 An individual's treatment and services plan must be assessed continually and
modified as necessary to ensure that it meets his or her changing needs.
 Treatment does not need to be voluntary to be effective. Sanctions or enticements
from family, employment settings, and/or the criminal justice system can significantly
increase treatment entry, retention rates, and the ultimate success of drug treatment
interventions.
 Drug use during treatment must be monitored continuously, as lapses during
treatment do occur. Knowing their drug use is being monitored can be a powerful
incentive for patients and can help them withstand urges to use drugs.
 Treatment programs should test patients for the presence of HIV/AIDS, hepatitis
B and C, tuberculosis, and other infectious diseases as well as provide targeted
risk-reduction counseling, linking patients to treatment if necessary.
 52a. General principles and regulation of drug prescription.

Principles:
All prescribers should:

1. Be clear about the reasons for prescribing

 Establish an accurate diagnosis whenever possible (although this may often be difficult)
 Be clear in what way the patient is likely to gain from the prescribed medicines

2. Take into account the patient’s medication history before prescribing

 Obtain an accurate list of current and recent medications (including over the counter and
alternative medicines); prior adverse drug reactions; and drug allergies from the patient, their
carers, or colleagues

3. Take into account other factors that might alter the benefits and risks of treatment

Consider other individual factors that might influence the prescription (for example,
physiological changes with age and pregnancy, or impaired kidney, liver or heart function)

4. Take into account the patient’s ideas, concerns, and expectations

Seek to form a partnership with the patient when selecting treatments, making sure that they
understand and agree with the reasons for taking the medicine

5. Select effective, safe, and cost effective medicines individualized for the patient

 The likely beneficial effect of the medicine should outweigh the extent of any potential harms,
and whenever possible this judgement should be based on published evidence
 Prescribe medicines that are unlicensed, ‘off label’, or outside standard practice only if satisfied
that an alternative medicine would not meet the patient's needs (this decision will be based on
evidence and/or experience of their safety and efficacy)
 Choose the best formulation, dose, frequency, route of administration, and duration of
treatment

6. Adhere to national guidelines and local formularies where appropriate

 Be aware of guidance produced by respected bodies (increasingly available via decision support
systems), but always consider the individual needs of the patient
 Select medicines with regard to costs and needs of other patients (health care resources are
finite)
 Be able to identify, access, and use reliable and validated sources of information (for
example, British National Formulary), and evaluate potentially less reliable information critically

7. Write unambiguous legal prescriptions using the correct documentation

 Be aware of common factors that cause medication errors and know how to avoid them

8. Monitor the beneficial and adverse effects of medicines

 Identify how the beneficial and adverse effects of treatment can be assessed
 Understand how to alter the prescription as a result of this information
 Know how to report adverse drug reactions (in the UK via the Yellow Card scheme)

9.Communicate and document prescribing decisions and the reasons for them

 Communicate clearly with patients, their carers, and colleagues

 Give patients important information about how to take the medicine, what benefits might
arise,
 adverse effects (especially those that will require urgent review), and any monitoring that is
required
 Use the health record and other means to document prescribing decisions accurately

10.Prescribe within the limitations of your knowledge, skills and experience

 Always seek to keep the knowledge and skills that are relevant to your practice up to date
 Be prepared to seek the advice and support of suitably qualified professional colleagues
 Make sure that, where appropriate, prescriptions are checked (for example, calculations of
intravenous doses)
Regulation:
Food and Drug Administration Agency (FDA) reviews the safety and effectiveness of new
drugs that manufacturers wish to market in the United States; this process is called
premarket approval or preapproval review. Second, once a drug has passed that threshold
and is FDA-approved
 53a. The peculiarities of prescribing of narcotics and psychotropic medications.
Rules for prescribing narcotics:

All of the following must be included in a prescription for a controlled substance 1:

 Issue date.
 Name and address of patient.
 Name, address, and DEA registration number of practitioner.
 Drug name.
 Strength of drug.
 Dosage form (i.e., tablet, suspension, etc)
 Quantity prescribed.
 Directions for use.

always try to use non-narcotic drugs first for pain management, if narcotics are
used, minimal therapeutic dose is given
Indications: Traumatic shock, Myocardial infarction (used together with atropine),
colic(used together with atropine), pain associated with cancer, pain after surgeries, pre-
anesthetic medication, pulmonary edema, cough dangerous for life (danger of pulmonary
bleeding or pneumothorax) Psychotropic medications are Neuroleptics, anxiolytics, and
sedatives and are drugs for the treatment of psychic disorders of different severity.
Neuroleptics (major tranquilizers) are the strongest among these preparations and have an
antipsychotic action .
Anxiolytics (minor tranquilizers) are characterized by anxiolytic and sedative effects.
Sedative drugs are the least potent and have only a sedative effect. Lithium salts are specific
agents to treat mania.
The cataract-analgesia is the kind of general anesthesia when the tranquilizer and
the narcotic analgesic are administered together (IV).
‘KPHARMA’

SECOND EXAM QUESTION

1b. Inhaled general anesthetics, their pharmacodynamics and use, comparative
characteristics.
Inhaled general anesthetics are the drugs that can be inhaled to produce the anesthetic
condition.

CLASSIFICATION

 Volatile liquids -Ether of narcosis, Halothane , Isoflurane , Sevoflurane )

 Gaseous anaesthesia -nitrous oxide , xenone
Mechanism of action Inhaled general anesthetics dissolve in the cell membrane lipids
resulting in the inhibiting of neurotransmission.
They Bind to lipid membrane causing a change in membrane viscosity which leads to Change
in the permeability of ion channels causing decrease in depolarization and Inhibition of
neurotransmitters resluting to narcosis.
Comparative character
Ether for narcosis is a volatile inflammable liquid with specific odor (permanent marker);
80% of dose is excretedunchanged with the air, has a wide safety margin of the narcosis
action, but a long stage of excitement; is used for basis mono- and combined narco-sis;
irritates the upper respiratory pathways; may cause pneumonia after the surgery.
Halothane (Phthorotanum) is a volatile liquid; contains fluorine; is not inflammable; has a
strong narcosis action , but weak analgesia; has long stage of analgesia without the
excitement stage; dilates bronchi (may be used for the termination of a severe bronchial
asthma attack); dilates blood vessels; lowers BP; increases the myocardium sensitivity to
catecholamines (adrenaline and noradrenaline are contraindicated during this narcosis);
decreases the tone of uterus; is metabolized in the liver and may cause liver lesion; is used
for combined general anesthesia.
Isoflurane is similar to halothane; displays good myorelaxation and rapid recovery; has a
lessnegative influence on the heart and liver; is the best agent in Pediatric patients.
Sevoflurane is a sweet-smelling, non-flammable, highly fluorinated methyl isopropyl ether
used as an inhalational anesthetic for induction and maintenance of general anesthesia; has
fast onset and offset; is one of the most commonly used volatile anesthetic agents,
particularly for outpatient anesthesia, It is often administered in a combination with nitrous
oxide and oxygen.
‘KPHARMA’
Nitrous oxide is a gaseous anesthetic; is biologically inert has a weak narcosis action (is not
used as a sole anesthetic for surgeries); does not cause good myorelaxation; has strong
analgesia; a rapid onset of action and recovery; is used for analgesia in traumas, myocardial
infarction, or labor, as well as for inductive and combined narcosis; is not toxic; may cause
hypoxia in concentration about 80%.
Xenon is the inert gas giving rapid induction and recovery in general anesthesia. The most
important positive effects of Xenon are cardiovascular stability, cerebral protection and
favorable pharmacokinetics.

Inhalation anesthetics Intravenous anethetics

–Inhalation administration –IV administration

–Long duration of narcosis –Short duration of narcosis

–Strong myorelaxation –Weak myorelaxation

–Well managed anesthesia –Unmanaged anesthesia

–Usage for cavitary surgeries –Usage for short uncavitary surgeries

2b. Injectable anesthetics, its pharmacodynamics, comparative characteristics and

therapeutic use.

Intravenous anesthetics are drugs for general anesthesia which are administered IV.

CLASSIFICATION

❖ According to the duration of action

• Long acting (more than 60 min) – Sodium hydroxibutyrate

• Intermediate-acting (20-30 min) – Thiopental sodium, used for the induction to narcosis,
general anesthesia in short-term surger-ies and diagnostic investigations

• Short-acting (10–20 min) – Ketamine (Ketamini hydrochloridum, Kalipsol), used for starting
and maintaining of anesthesia, for chronic pain and for sedation in the intensive care. used
in children, in patients with shock or low BP, asthmatics or people with chronic obstructive
airway disease, emergency surgery in field conditions in war zones, and to supplement spinal
or epidural anesthesia.

• Ultra-shortacting (3-5 min) – Propofol

❖ According to the mechanism of action

GABAergic

– Sodium hydroxibutyrate

– Propofol, Used for induction and maintenance of anesthesia, Antiemetic, CNS and cardiac
depressant

Barbiturate-ergic
 – Thiopental-sodium

Glutamateergic

–Ketamine,

Pharmacodynamics: Potentiation of GABAA receptors increases chloride ion conductance, resulting

in inhibitory post-synaptic currents and ultimately inhibition of neuronal activity.
Therapeutic use: Intravenous anesthetics are used both to induce and maintain general anesthesia
in the operating room, for sedation and anxiolysis preoperatively, for procedures outside the
operating room.
Sodium hydroxybutyrate the drug is the analogue of GABA (natural inhibiting neurotransmitter).
Pharmacokinetics is administered IV, IM, orally begins to act in 5-7 min after IV administration acts
during 2-4 hrs is completely metabolized in the body.

 action Sodium oxibutyrate stimulates GABA-receptors of Cl–channels (fig.9.7). A result is the

opening of Cl– channels and an increase in Cl– influx into the cell. Increased Cl–
concentration leads to the hyperpolarization of the cell mem-brane and more difficult
depolarization. These processes result in the reduction of neurons excitability, sleep, and
general anesthesia.
 Pharmacodynamics: General anesthesia, A sedative action, A hypnotic action, An anti-
seizure action, An antihypoxic action, A nootropic action (after a long-term treatment).
 Side-effects The drug is not toxic, but may cause hypokalemia.
Thiopental sodium is administered IV; begins to act in 1-3 min; acts during 20- 30 min; is destroyed
in microsomes of the liver; is accumulated in the fat tissue;

 stimulates barbiturate receptors of CL-ion channels; displays a rapid onset of action; has
potent anesthesia, poor analgesia, and little myorelaxation; has a hypnotic action;
 is used for the induction to narcosis, general anesthesia in short-term surgeries and
diagnostic investigations;
 Side effect- suppression of respiration, apnea, bronchospasm, laryngospasm, hypotension,
arrhythmia, liver lesions, lowering of the body temperature, thrombophlebitis;
 is contraindicated in the heart failure, bronchial asthma, diseases of the upper respiratory
pathways, shock, acidosis.

Ketamine is administered IV, IM; begins to act in 30-60 sec after administration; acts during 15-30
min; may be administered repeatedly in a lower dose.

 It acts primarily as a selective antagonist of the NMDA receptor. Also it is an agonist of

different subtypes of opioid receptors, the agonist of dopamine D2 receptor and potentiator
of 5-HT receptor, The drug causes “dissociate narcosis”;
 Effect: causes general anesthesia accompanied by strong analgesia during narcosis and after
it (6-8 hrs); stimulates blood circulation (increases heart rate, minute volume of the heart
and BP); does not inhibit respiration; does not cause myorelaxation and impairment of
reflexes; has psychotomimetic action at the start and at the end of narcosis;
 It is used for starting and maintaining of anesthesia, for chronic pain and for sedation in the
intensive care. The drug can be used in children, in patients with shock or low BP, asthmatics
or people with chronic obstructive airway disease, emergency surgery in field conditions in
war zones, and to supplement spinal or epidural anesthesia.
 side effects: may cause postoperative hallucinations, muscles regidity, block of upper
respiratory pathways, psychomotor excitement; is contraindicated for patients with
hypertension and disturbances of cerebral blood circulation. It can cause drug dependence
and is strongly controlled substance.
Propofol is a short-acting IV general anesthetic. It has several mechanisms of action, both through
 activation of GABAA receptor and acting as a sodium channel blocker. Endocannabinoid system may
contribute significantly to propofol's anesthetic action.

 uses include the starting and maintenance of general anesthesia, sedation for mechanically
ventilated adults, procedural sedation, and status epilepticus. Maximum effect takes about 2
min to occur and lasts 5-10 min.
 Common side effects are irregular heart rate, low BP, burning sensation at the site of
injection, and the stopping of breathing. The drug may cause addiction and propofol infusion
syndrome.

3b. Pharmacodynamics and therapeutic use of ether group of localanesthetics:Anaesthesinum

(Benzocaine) and Novocaine (Procaine).
CLASSIFICATION
Esters of para-aminobenzoic acid
– Procaine (Novocainum)
– Benzocaine (Anaesthesinum)
– Tetracaine (Dicainum)
Procaine (Novocainum) is an ester; given ORALLY, it can dilates blood vessels; is used for
infiltration, conductive and spinal anesthesia; other indications are spasms of blood vessels
and smooth muscles, pain syndromes, arrhythmia, toxicosis of pregnancy; may cause
allergic complications including anaphylaxis, collapse, hypotension, seizures (in overdose).
Uses – used as lozenges for stomatitis, sore throat ; as dusting powder/ ointment on
wounds/ ulcerated surfaces and as suppository for anorectal lesions. It is a derivative of
PABA, so it can antagonize sulfonamides locally. (lozenges-rhombus shaped medication)

Benzocaine (Anaesthesinum) is an ester; given by INJECTION, is less active than procaine; is

not dissolved in water; is used only for surface anesthesia in burns, wounds, diseases of skin
and mucous membranes; is not toxic, but may cause methemoglobin formation when is
used on large areas of skin lesions.
Uses – used to numb a particular part of the body. In dental procedure to numb the area
around a tooth.

Lidocaine (Xycainum) is the amide; acts longer than procaine; is more active; is suitable for all types of anesthesia; is used
for the treatment of ventricular tachyar-rhythmia (IV). Trimecaine is an amide; pharmacological properties are similar to
lidocaine.

Bupivacaine (Marcaine) is an amide; is one of the most active local anesthetics; is used for infiltration, conductive and
spinal anesthesia; has toxic action on the heart.

Articaine is an amide; more active than lidocaine and procaine; acts during 1-5 hrs; is used for infiltration and conductive
anesthesia; is widely used in dentistry. Combination of articaine with vasoconstrictor is known as Ultracaine.

Tetracaine (Dicainum) is an ester; dilates blood vessels; is more active and more toxic than procaine; is used only for
surface anesthesia.
 ESTERS AMIDES

Short action long action

Metabolized by esterase in blood metabolised in liver

Not active at acid pH active at acid pH

Decrease effect of sulfa drugs do not interact

4b. Pharmacodynamics, therapeutic use of amide group of local anesthetics

(Xycaine=Lidocaine,Trimecaine).
Amide group of local anesthesia include
o Lidocaine
o Trimecaine
o Piromecaine
o Articaine, Ultracaine
o Bupivacaine (Marcaine)

Lidocaine(Lingocaine, xycainum)
is the amide; acts longer than procaine; is more active; is suitable for all types of anesthesia;
is used for the treatment of ventricular tachyar-rhythmia (IV).
Mech.OfAct. – act by blocking of voltage-gated sodium channels leading to a reversible
block of action potential propagation.
Uses – used for surface application, infiltration, nerve block, epidural, spinal and
intravenous regional block anesthesia. Numb and relieve pain form minor burns (including
sunburns), skin abrasions, insect bites, and painful condition of mucous membrane. In
dental procedure.

Bupivacaine (Marcaine) A potent and long-acting amide-linked: used for infiltration, nerve
block, epidural and spinal anaesthesia of long duration. A 0.25–0.5% solution injected
epidurally produces adequate analgesia.
Used in obstetrics (mother can actively cooperate in vaginal delivery) and for postoperative
pain relief by continuous epidural infusion.
It has high lipidsolubility; distributes more in tissues than in blood after spinal/epidural
injection. Therefore, it is less likely to reach the foetus (when used during labour) to
produce neonatal depression.
Bupivacaine is more prone to prolong QTc interval and induce ventricular tachycardia or
cardiac depression—should not be used for intravenous regional analgesia.
Epidural anaesthesia can cause cardiac arrest.

Articaine is an amide; more active than lidocaine and procaine; acts during 1-5 hrs; is used
for infiltration and conductive anesthesia; is widely used in dentistry. Combination of
articaine with vasoconstrictor is known as Ultracaine.
Trimecaine: pharmacological properties are similar to lidocaine. is also used for prophylaxis
and therapy of ventricular arrhythmia in myocardial infarction and in cardiac surgery. It is
also used for prophylaxis of sympathetic reaction during tracheal intubations.

5b. Acute intoxication with local anesthetic, its treatment and prevention.
(1) CNS effects are light-headedness, dizziness, auditory and visual disturbances, mental
confusion, disorientiation, twitching, involuntatory movements and respiratory arrest.

(2) Cardiovascular toxicity is manifested as bradycardia, hypotension, cardiac arrhythmia.

(3) Injection of LAs may be painful, but local tissue toxicity of LAs is low. However, wound
healing may be sometimes delayed. Addition of vasoconstrictors enhances the local tissue
damage, rarely necrosis results.

(4) Hypersensitivity reactions like rashes, angioedema, dermatitis, contact sensitization,

asthma occur.

Treatment and prevention:-

1. Before injecting the LA, aspirate lightly to avoid intravascular injection.
2. Inject the LA slowly and take care not to exceed the maximum safe dose, especially in
children.
3. Propranolol (probably other β blockers also) may reduce metabolism of lidocaine and
other amide LAs by reducing hepatic blood flow.
4. Vasoconstrictor (adrenaline) containing LA should be avoided for patients with ischaemic
heart disease, cardiac arrhythmia, thyrotoxicosis, uncontrolled hypertension, and those
receiving β blockers (rise in BP can occur due to unopposed α action) or tricyclic
antidepressants.

6b. Astringents, slime agents and absorbents, irritants: mechanism of action, therapeutic
use.
Astringents are the agents that precipitate protein and form albuminates on the surface of
the damaged skin or the mucous membrane, thus protecting the receptors from irritating
factors and relieving pain.
CLASSIFICATION
Organic substances
– Tannin
– Tanalbinum
– herb of Saint-John’s-wort (herba Hyperici)
– flowers of chamomile (flos Chamommillae)
 – leaves of salvia (folium Salviae)
– bark of oak (Cortex Quercus)
Non-organic substances
– Bismuth subnitrate.

 Tannin is an organic astringent; is used in the form of solution, ointment, powder for
external use; has astringent and anti-toxic action (is an antidote in poisonings with
alkaloids and salts of metals); is used for gargling in diseases of oral mucose, for
processing of burns, for lavage of stomach in acute poisonings; may disturb digestion if it
is taken orally.

 Tanalbinum is a compound of tannin; is taken orally to treat dyspepsia, enteritis,

enterocolitis; does not bind to enzymes in the gut and does not disturb digestion.

 Bark of oak (Cortex Quercus) is used in the form of decoction; is applied for gargling
in stomatitis, gingivitis, paradontitis; may be also used to treat burns, wounds.

 Leaves of salvia (Folium Salviae), herb of sant-john’s-wort (Herba Hyperici), flowers

of chamomile (Flos Chamommillae) are used in the form of infusions; they have
astringent, anti-inflammatory, antimicrobial effects, stimulate regeneration of tissues;
indications are similar to indications for the use of the oak bark; are widely used in
dentistry.

 Bismuth subnitrate is non-organic astringent; is taken orally in ulcer of the stomach

and duodenum, enterocolitis; is applied topically to treat wounds, ulcers, and burns of
skin.
Slime agents and Adsorbents : are insoluble fine powders which have a large active surface
capable fixing irritating and poisonous substances dissolved in water and gases, thus
preventing their absorption in the GIT and protecting receptors.
Example: Carbo activatus(activated carbon). Administered orally in the case of acute
poisoning, enteritis, dyspepsia and meteorism.

Irritants – irritants stimulate sensory nerve endings and induce inflammation at site of
application. They produce cooling sensation or warmth, prickling and tingling,
hyperesthesia or numbness and local vasodilation.

7b. Anticholinesterase drugs: mechanism of action, pharmacodynamics, therapeutic useand

side effects.
Anticholinesterases are indirect-acting M-, N-cholinomimetics with a reversible or
irreversible type of action.
Mechanism of action Anticholinesterases bind to acetylcholinesterase in the synaptic gap,
inhibit it and decrease acetylcholine destruction. The result is the accumulation of the
acetylcholine amount in the synaptic gap and an increase in acetylcholine interaction with
M- and N-cholinoreceptors

Pharmacodynamics:
- all M-cholinomimetic effects on internal organs (similar to those of carba-chol
and pilocarpine)
- an increase in neuromuscular transmission resulting from the
- accumulation of acetylcholine at the neuromuscular junction.
classification

1. reversible anticholinesterases
(i) short acting(Alcohols) – Edrophonium
(ii) intermediate acting (carbamates esters) – Physostigmine, Neostigmine, Pyridostigmine,
Ambenonium
2. irreversible anticholinsterases – phosphates esters : Ecothiophate and Isoflurophate.

Therapeutic uses:-
Physostigmine is used for the treatment of glaucoma, intoxication by atropine,
cholinoblockers, and tricyclic antidepressants, early stages of Alzheimer’s disease; is toxic.
is an alkaloid; is well absorbed; penetrates CNS; has a reversible anticholinesterase action;

Galantamine is used for the treatment of paralysis, neuritis, early stages of Alzheimer’s
disease and other neurological diseases; is not used in glaucoma due to its irritative action.
is an alkaloid; is administered SC, IM; penetrates into CNS; has a reversible anticholinesterase action.

Neostigmine is used for paralysis, neuritis, myasthenia gravis, atonia of the intestine and urinary
bladder, some kinds of arrhythmia, glaucoma, poisoning with atropine, overdose oftubocurarine; may
be used for stimulation of labor activity; in dentistry is applied for xerostomia; is less toxic than
physostigmine is a synthetic preparation; is administered orally, SC, IV, topically (eye drops); does not penetrate CNS; has
a reversible anticholinesterase action (4-6 hrs);

Pyridostigmine acts longer, but is less potent than neostigmine; is used orally for the
treatment of neurological diseases and myasthenia gravis.
Phosphacolum is an irreversibly acting anticholinesterase with long-lasting action; is toxicand
used only for glaucoma (eye drops).
Side effects: same as direct M-,N-, and M- cholinomimetics like pain in abdomen,
bradycardia, frequent urination , diarrhea, hypersalivation, sweatiness, spasm of bronchi.
8b. M-cholinoblockers: mechanism of action, pharmacodynamics, therapeutic use and
side effects.
M-cholinoblockers are the drugs which block neurotransmission in the muscarinic synapses
of the parasympathetic nerves and decrease the effects of parasympathetic innervation.
They also block M-cholinoreceptors in sympathetic neurons innervating sweat glands.
CLASSIFICATION

A. Non-selective
1.Natural agents:
– Atropine sulfate

– Hyoscine (Scopolamine hydrobromide)

– Platyphylline hydrotartrate – Belldoonna dry extract

2. Synthetic and semisynthetic agents :

– Butylscopolamine (buscopan)

– Prifinium bromide (riabal)

– Ipratropium bromide (Atrovent)

– Tropicamide

B. Selective

– Pirenzepine (Gastrocepine), darifenacin, methoctramine, himbacine.

MECHANISM OF ACTION

If we talk about atropine sulfate, Atropine competes reversibly with acetylcholine at M-

cholinoreceptor. It binds to receptors and prevents binding of acetylcholine to these sites.

Atropine has a non-selective action: it interacts with all the subtypes of M-cholinoreceptors.

Atropine is both a central and peripheral muscarinic blocker.

Pharmacodynamics

- CNS : therapeutic dose- a sedation and ant parkinsonism effect, large doses- excitation,

hallucinations, coma.

- Eye: dilatation of pupils (mydriasis), inability to focus for near vision (cycloplegia, paralysis

of accommodation), increase intraocular pressure

- Cardiovascular: tachycardia

- Respiratory: dilation of bronchi and decrease in bronchial gland secretion

- Gut: reduce saliva and gastric secretion, decrease tone and motility, antispasmotic activity

- Urinary system: relaxation of smooth muscles of urinary bladder

- Inhibition of sweat secretion

- Antidote in poisoning wit m-cholinomimetics, anticholinesterase and toxic mushrooms

containing muscarine.

THERAPEUTIC USES

- Trauma of the eye, inflammation in the eye (cycloplegia and midriasis are

“pharmacological bandage” producing eye immobilization)

- Diagnostics of eye diseases, the measurement of refraction for the correct

selection of glasses Bradycardia,

 - AV block Hypersalivation

- Gastric ulcer, Acute pancreatitis, Cholecystitis, Billiary or renal colic Enuresis

Premedication Acute poisoning with muscarine-containing mushrooms,

- M-cholinomimetics, anticholinesterases, or morphine.

SIDE EFFECTS

Dilated pupils resulting in photophobia

Blurred vision

An increase in intraocular pressure, an attack of glaucoma in someone with latent condition

Tachycardia

Dry mouth
Constipation, Retention of urine, Flushed skin, A rise in body temperature.

CROSS QUE --
Scopolamine is alkaloid. It has pharmacokinetics and peripheral effects similar to
atropine; the central action is greater and longer than that of atropine; inhibits
activity of VIII pair of cranial nerves and decreases motion sickness, produces
sedation and short memory block-ing, has antiparkinsonian effect; has a strong and
short (5-6 hrs) action on the eye; is used for the prevention and treatment of motion
sickness, for the complex therapy of psychic diseases, Parkinson’s disease, for
premedication; has side-effects similar to those of atropine.

Platyphylline is alkaloid; has the central action less than that of atropine; has a short
(5-6 hrs) action on the eye; causes
inhibition of the vasomotor center and a direct myotropic action on blood vessels,
that’s why dilates blood vessels and lowers BP; may be used to treat spasms of
cerebral and coronary blood vessels, as well as to treat hypertension.

Preparations of Belladonna (extracts, tinctures) are used as antispasmodic and

analgesic agents for stomach ulcer,
cholelithiasis and other diseases accompanied by spasms of smooth muscles of the
abdominal cavity organs, bradycardia due to overexcitation of n. vagus nerve. They
are the ingredients of some combined preparations.

Butylscopolamine is a semisynthetic derivative of scopolamine which does not

penetrate blood-brain barrier and has not central action. It is used to treat crampy
abdominal pain, esophageal spasms, renal colic, and bladder spasms. The drug is
effective in reducing the duration of the first stage of labor. Side effects may include
sleepiness, vision changes, triggering of glaucoma, and allergy.

Prifinium bromide (riabal) is slowly absorbed into the gut and quickly excreted;
blocks peripheral M-cholinoreceptors in the GI tract that leads to inhibition of acid
secretion and peptic activity of gastric juice; reduces the exocrine activity of the
pancreas, the tone of the smooth muscles of the gut, normalizes the peristalsis of
the stomach, corrects increased motor activity of the GI tract. The drug is used in
 nausea and vomiting caused by functional spasms in infants, abdominal pain
syndrome with functional disorders of the colon; spasms of smooth muscles of the
gastrointestinal tract. Side effects are dry mouth, mydriasis, disturbances of accom-
modation, drowsiness.

Ipratropium bromide is quaternary derivative of atropine, non-selective M-

cholinoblocker in the form of aerosol; is not absorbed in lungs and acts on M-
cholinoreceptors only in bronchi; dilates bronchi; is used for prevention of bronchial
asthma attack; has not significant side effects (may cause unpleasant taste).

Pirenzepine is selective M1-cholinoblocker inhibiting gastric secretion; is

administered orally, IM, IV; produces maximal
concentration in blood plasma in 2-3 hrs after oral administration; has a half-life of
10-12 hrs; does not penetrate CNS and placenta;
is used for treatment of ulcer of stomach and duodenum, Zollinger-Ellison’s
syndrome, prevention of peptic ulcers caused by stress; may cause dry mouth,
blurred vision, retention of urine but side effects are minimal in comparison with
atropine.

Tropicamide blocks the M-cholinoreceptors of the sphincter in the iris and ciliary muscle,
causing short-term mydriasis and accommodation paralysisis; is used in ophthalmology for
examination of the ocular fundus, investigation of refraction, as well as in inflammatory
processes of the eye. It is applied as eye drops.

9b. Comparative characteristics of the drugs: atropini sulfas, plathyphyllini hydrotartras,

scopolamine hydrobromidum, Ipratropium bromide, Pirenzepine.
Atropine sulfate – obtained from medical plants such as Atropa belladonna. Administered
orally, IM, SC or topically. Penetrates CNS and placenta. Metabolized in liver and excreted
with urine. Atropine reversibly competes with acetylcholine at M-cholinoreceptor.

 It binds to receptors and prevents binding of acetylcholine to these sites. Block

neurotransmission in muscarinic synapse of parasympathetic nerves and decrease
effects of parasympathetic innervation.
 It is used in cycloplegia and mydriasis, bradycardia, AV block, hypersalivation, gastric
ulcer, acute pancreatitis, cholecystitis, eneuresis. Cycloplegia is paralysis of the
ciliary muscle of the eye, resulting in a loss of accommodation
Plathyphyllini hydrotartras – it is alkaloid has central action. Cause inhibition of vasomotor
center and direct myotropic action on blood vessels, so dilates blood vessels and lowers BP.
Used to treat spasm of cerebral and coronary blood vessels
It is used in the form of a powder or solution to treat bronchial asthma, muscle spasms of
the abdominal organs, and vascular spasms. Platyphylline is also used to dilate the pupils.
Scopolamini hydrobromidum – its pharmacokinetic and peripheral effcts are similar to
atropine. Inhibit activity of VIII pair of cranial nerves and decrease motion sickness , produce
sedation and short memory blocking, has antiparkinsonian effect. Used for treatment and
prevention of motion sickness.

 Given ORALLY or IM
Ipratropium bromide – it is derivative of atropine, non-selective M-Cholinoblockers in the
forms of aerosols. Used for prevention of bronchial asthma, it has no significant side effects.
Pirenzepine – it is selective M1-cholinoblocker inhibiting gastric secretion, produce maximal
concentration in blood plasma after orally. Do not penetrate CNS and placenta. Used for
peptic ulcer by stress, Zollinger-Ellison syndrome.
Only pirenzepine is selective cholinoblocker.all other are non selective.
10b. Ganglion blockers: mechanism of action, indication and contra-indication for use,
typicalcomplications.
Ganglion blockers are preparations which block N-cholinoreceptors in ganglia.

Classification
1. Quaternary amines
- Hexamethonium (benzohexonium) hypertensive emergency, controlled
hypotension in surgery, edema of lungs, edema of brain, bronchial asthma attack,
colic

- Hygronium : short acting, only I.V, used for controlled hypotension in surgeries,
edema of lungs, edema of brain, severe hypertensive crisis.

- Pentaminum : only I.V and I.M, acute hypertension, bronchial asthma attack, colic,
controlled hypotension in surgery

2. Tertiary amines
- Pachycarpine hydroiodide : taken oral, treat gangliolitis, spasm of peripheral blood
vessel, bronchial asthma

- Pirilenum : oraly, I.M, S.C, stimulates uterus contractions, improves functions of

skeletal muscles, treat gangliolitis, spasm of blood vessels, nervous diseases,
myopathy, may be used for stimulation of labor activity.

MOA – They blocks N-cholinoreceptors in the sympathetic and parasympathetic ganglia and
disturbs autonomic regulation of internal organs. It inhibit propagation of nervous impulses
running to effector organ along both sympathetic and parasympathetic fibers.

Side effects : hypotension, orthostatic collapse, dry mouth, constipation, retention of

urination, increase intraocular pressure

Contraindication : Hypotension, collapse, severe atherosclerosis, closed angle glaucoma,

atony of gut, adenoma of prostate, severe diseases of heart, liver and kidneys.

11b. Neuromuscular blockers (myorelaxants): mechanism of action, pharmacodynamics,

therapeutic use.
Myorelaxants (neoromuscular blockers) are cholinergic drugs which interfere with the
transmission of nervous impulses in the synapses of skeletal muscles causing their
relaxation.
CLASSIFICATION
Non-depolarizing agents
– d-Tubocurarine chloride
 – Pancuronium bromide
– Pipecuronium bromide
– Rocuronium bromide
Depolarizing agents

- Succinylcholine (Dithylinum).

MECHANISM OF ACTION
It binds to endplate N-cholinoreceptors without exciting them and acts as a competitive
antagonist towards acetylcholine. It blocks neuromuscular transmission by the prevention of
acetylcholine binding to such nicotinic receptors.
PHARMACODYNAMICS
muscular paralysis which occurs firstly in the muscles of fingers, neck, face, extremities,
trunk, then in intercostal muscles, and the diaphragm (with the inability to breath).
THERAPEUTIC USE
- myorelaxation under the conditions of general anesthesia
- seizures caused by seizure poisons and some infections.

SIDE EFFECTS : Spasm of bronchi and urticaria (due to histamine release from mast cells) Lowering of BP (due to weak
ganglia blocking activity).

Contraindications: Myasthenia gravis, bronchial asthma, childhood.

Decurarization The duration of the action of d-tubocurarine can be shortened by the administration of neostigmine.
Inhibition of acetylcholine esterase causes the concentration of acetylcholine released at the endplate to rise. Competitive
“displacement” by acetylcholine of tubocurarine from the receptors allows transmission to be restored.

Pancuronium is a synthetic compound, is more potent than tubocuracine, has a longer duration of action, does not cause
release of histamine or ganglionic blockade, may cause an increased heart rate and BP (due to blockade of M2 cardiac
receptors).

Pipecuronium is similar to pancuronium, does not cause tachycardia and an increase of BP.

Rokuronium is an antagonist of n-cholinergic receptors of skeletal musculs; inhibits neuromuscular transmission and
causes myorelaxation, has weak vagolytic effect, does not affect the release of histamine. The duration of the effect is 22
min in adults.

12b. Pharmacodynamics, mechanism of action and use of adrenaline (norepineprine), its

side effects.
Adrenaline is a catecholamine produced by adrenal medulla (sc, i/v)
Mech.of.action: adrenaline acts by stimulation of all types of adrenoceptors.
Through its action on alpha-1 receptors, epinephrine induces increased vascular smooth
muscle contraction, pupillary dilator muscle contraction, and intestinal sphincter muscle
contraction. Other significant effects include increased heart rate, myocardial contractility,
and renin release via beta-1 receptors
Pharmacodynamics : An increase in automaticity, conductivity and contractility of the heart,
constriction of blood vessels, elevation of blood pressure, bronchodilation, increase in
glucose concentration in blood, inhibition of allergy, mydriasis , decrease intraocular
pressure
Indications : heart arrest, prolongation of local anesthesia, acute inflammation of mucous
membrane of nose or the eye. Shock, collapse, bronchial asthma attack, hypoglycemic
coma, anaphylactic shock, pupil dilation, open-angle glaucoma.
Side effects: excitement, tremor, hypertension, arrhythmia, hyperglycemia

13b. Pharmacodynamics, mechanism of action and use of ephedrine, its side effects.
Ephedrine and pseudoephedrine are mixed-action adrenergic agents. They not only release
stored norepinephrine from nerve endings but also directly stimulate both α and β
receptors
Pharmacodynamics – Stimulation of CNS, increase ability to physical and mental work,
euphoria, stimulation of heart function, vasoconstriction, elevation of BP, dilation of
bronchi, inhibition of gut motility, retention of urine, mydriasis.

Mech.of.action - Ephedrine stimulates release of norepinephrine, inhibits reuptake of

norepinephrine. It has a weak direct action on adrenoreceptors. (SC,IM, IV, topically).

Use – Shock, collapse, anaphylactic shock, bronchial asthma, bronchospasm, AV block,

bradycardia, Acute rhinitis, Acute conjunctivitis, pupil dilation, pathological narcolepsia,
myasthenia, enuresis.

Side effects – Insomnia, anxiety, restlessness, tachycardia, palpitation, hypertension, rash

on skin, tolerance and tachyphylaxis, drug dependence.
The drug should not be used in sportsmen as a doping.

14b. Pharmacological characteristic of Noradrenaline, Adrenaline, Mesaton

(phenylephrine), Izadrine(Isoproterenol) and Salbutamol.
Noradrenaline, Adrenaline,isoprotenol-catecholamines(can’t traverse through cns)

Salbutamol, mesaton-non catecholamines.

1. Adrenaline :
-is administered SC,IV,intracardially,topically;
-does not penetrate CNS;
-stimulates all adrenoreceptors;
-increase automaticity,conductivity and contractility of the heart;constricts blood
vessels;elevation of BP;bronchodilation;inhibition of allergy;mydriasis;increases glucose in
blood;

-using:cardiac arrest;shock;collapse;bronchial asthma attack;hypoglycemic coma;pupil

dilatation;anaphylactic shock;

-side effects:hypertension; hyperglycemia; arrhythmia; tremor, excitement;

-contraindication: hypertension; atherosclerosis; heart; arrhythmia;hyperthyroidism

2. Noradrenaline:
-non selective action on adrenoreceptors;has a short durative action;
-is administered SC,IM and IV

Vasoconstriction: Norepinephrine causes a rise in peripheral resistance due to intense

vasoconstriction of most vascular beds, including the kidney (α1 effect). Both systolic and
diastolic blood pressures increase
-infusion used in hypotension and collapse
-is controindicated in blood loss,cardiogenic shock

3. Mesotonum: Phenylephrine
-is a non cathecolamine;
-has a selective action on alpha1-Adrenoreceptor
-may be takken orally,SC,IV,IM,topically;
-used for acute and chronic hypotension;to decrease edema in acute rhinitis or conjuctivitis
Phenylephrine is also used in ophthalmicsolutions for mydriasis

4. Salbutamol:
-is a non catecholamine;
-has a selective action on beta2-AR;
-is used in bronchial asthma,bronchospasm and before bronchoscopia

5. Isadrine (isoprotenol):
-is a synthetic catecholamine;
-has a selective action on beta2-AR and beta1-AR;
-is administered sublingually,by inhalation,IV;
used for the treatment of bradycardia (slow heart rate), heart block.

15b. α-adrenoblockers: pharmacodynamics, mechanism of action and use, side effects.

Drugs of Alpha-Adrenoblockers :
1. Non-selective: Phentolamine hydrochloride, Trophenum
2. Selective: Prazosin, Doxasin, terazosin

Mechanism of action: possess a competitive mechanism of blocking effect, through their

structural similarity to catecholamines they block presynaptic alpha2-AR and postsynaptic
alpha1-adreno-receptors. They binds to α-adrenorecptors and make impossible interactions
between the norepinephrine and adrenorecptors.

Pharmacodynamics:
Reduce peripheral resistance, increase venous capacity, decrease BP, improve trophy of
peripheral tissues, stimulate gut motility, stimulate salivary, lacrimal, pancreatic and
respiratory tract secretions, decrease of urine retention.

Indications : hypertension, spasm of peripheral blood vessels (Raynaud’s disease),

Pheochromacytoms, prostate hyperplasia

Side effects : Headache, vertigo, hypotension(posture related), weakness, insomnia,

orthostatic collapse, tachycardia, vomiting, nausea, diarrhea, rhinitis.

16b. β-adrenoblockers: pharmacodynamics, mechanism of action and use, side effects.

They are preparations which bind to β-adrenoceptors and prevent their stimulation by
norepinephrine
Drugs are :-
1. Non-selective – Propranolol (Anaprilin) , Oxprenolol
MOA: they block beta-1 adrenoreceptor in the heart and beta-2 adrenoreceptor in
other organs(blood vessels, bronchi).

2. Selective - Metoprolol , Atenolol, Nebivolol, Bisoprolol

MOA: selectively block beta-1 receptors

Pharmacodynamics:-
● a decrease in automaticity of myocardium
● a decrease in excitability of myocardium
● a decrease in conductivity of myocardium
● a decrease in the heart rate (anti -arrhythmic effect)
● decreases the heart contractility, striking and minute volume
● a decrease in the consump;on of oxygen by myocardium (antianginal effect)
● a decrease in the renin’s secretion in the kidney
● the lowering of BP (antihypertensive effect)
● the lowering of intraocular pressure
 Uses :-
1) Anaprilin used in hypertension, ischemic heart disease (angina pectoris, MI) ,
Migraine , glaucoma, hyperthyroidism, supraventricular tachyarrhythmia
2) metoprolol : HTN, angina pectoris, arrhythmia
3) talinolol: cardioselective action on beta 1 receptors, membrane stabilizing effect
(doesn't inhibit heart contractility and conductivity)
4) atenolol: same as metoprolol
5) nebivolol : treat chronic HTN and as a part of combined therapy of CHF in old
patients -
6) bisoprolol : for chronic HTN, angina pectoris, CHF
side effects : bradycardia, heart block, hypotension, spasm of bronchi , fatigue, vertigo,
depression, disturbances of sexual function in men, increasing of heart incompetence,
drowsiness.

17b. Sympatolytics: drugs, pharmacodynamics, mechanism of action and use, side effects.
Sympatolytics are the adrenergic antagonists of presynaptic action
Drugs:
1. Alpha2 AGONIST(centrally acting symphatholytic)-clonidine,methydopa(centrally
converted to norepinephrine to decrease adrenergic outflow)

2. Adrenergic receptor blocker:

* Beta non selective blocker-propanolol lebatelol
* Beta1 blocker (cardioselective) – metoprolol atenolol acebutolol
* Alpha1 blocker- prazosin, terazosin doxazosin

3.Adrenergic neuron blocker-guanethidine.

4.Ganglionic blocker-trimethaphan
1.Reserpine :-

Moa : an alkaloid that decreases storage of norepinephrine that leads to destruction of

neurotransmitter by MAO in axonal cytoplasm resulting in decrease neurotransmission in
adrenergic synapse
Pharmacodynamics - antihypertensive, antipsychotic, sedative action. It penetrates CNS and
has central and peripheral action. It is administered IV, IM or orally
Use : in hypertension
Side effects : parkinsonian manifestation, somnolence, disturbance of sleep, depression,
bradycardia, spasm of bronchi, stimulation of gastric secretion, diarrhea
2.Octadine ( Guanethidine) :-
Moa - acts by displacing norepinephrine from postganglionic sympathetic nerve endings.
The drug depletes tissue stores of norepinephrine, decreases reuptake of norepinephrine by
the nerve terminals, and lowers sympathetic tone.
synthetic compound that produces active storage and uptake instead of norepinephrine,
decreases neurotransmitter release
Pharmacodynamics - antihypertensive action, decrease intraocular pressure
Use : for HTN, glaucoma, some types of arrhythmia
Side effects – orthostatic collapse, bradycardia, spasm of bronchi, stimulate gastric
secretion, nausea, vomiting, liquid retention, diarrhea, enlargement of salivary gland
2. Trimethaphan is a ganglionic blocking agent prevents stimulation of postsynaptic
receptors by competing with acetylcholine for these receptor sites. Additional effects may
include direct peripheral vasodilation and release of histamine

Common Pharmacodynamics:- All sympatholytic drugs inhibit stimulation of the

sympathetic nervous system, causing dilation of the peripheral blood vessels or decreased
cardiac output, thereby reducing blood pressure, has antihypertensive action, decreases
intraocular pressure, sedative and antipsychotic action.

19b. Opioid and non-opioid analgesics: mechanism of action, therapeutic use for different
types of pain.
Opioid analgesics are the drugs to relieve intense pain which increase the action of
endogenous opiopeptides and may cause drug dependence.
Mechanism of action
If we talk about morphine. Morphine stimulates all the types of opioid receptors. It has high
affinity for μ-receptors (mediate analgesia at supraspinal level) and some action for other
opioid receptors.
In such a way it suppresses neurotransmission in the nociceptive system that results in the
rising of pain threshold in the spinal cord and altering of the brain perception of pain.

USES
- Traumatic shock
- Myocardial infarction (together with atropine) Colic (together with atropine)
- Pain associated with cancer
- Pain after surgeries
- Pre-anesthetic medication
- Pulmonary edema
- Cough dangerous for life (the danger of pulmonary bleeding or pneumothorax).

Non-opioid analgesics are drugs for a decrease of intermediate and weak pain, especially
resulting from inflammation
Mechanism of analgesic action
Inhibition of COX by non-opioid analgesics leads to a decrease in the synthesis of
prostaglandins. That results in a decrease of the sensitivity of nociceptors to inflammatory
mediators and an increase of the pain threshold.
Such events cause a decrease in the transmission of pain impulses in CNS and relief of pain.
USES
- Rheumatism Fever
- Arthritis Headache, toothache, myalgia,
- neuralgia
- Gout
- Dysmenorrhea
- Prophylaxis of re-thrombosis, myocardial infarction, or insult Thombophlebitis
- Patent ductus artriosus Prevention of colorectal cancer.

20b. Opioid analgesics: drugs, pharmacodynamics, use, side effects.

Opioid analgesics are the drugs to relieve intense pain which mimic the action of
endogenous opioid peptides

Classification:
1. Strong agonists of opioid receptors

● Natural compounds– Morphine hydrochloride,codeine phosphate, omnoponum

● Synthetic compounds– Tremeperidine (Promedolum), Fentanyl (in anesthesia with
Droperidol),

2. Mixed agonists-antagonists and partial agonists of opioid receptors

– Pentazocine, Buprenorphine, Butorphanol , Nalbuphine, Nalorphine hydrochloride

3. Analgesics with opioid and non opioid mechanism of action: Tremadol hydrochloride

4. Antagonists of opioid receptors: Naloxone hydrochloride, Naltrexone

Pharmacodynamics-

 analgesia (a decrease in all the kinds of pain; changes in perception of pain –

sensation of pain is not unpleasant)-
 euphoria (sense of well being), then sleep
 potentiation of other drugs inhibiting CNS
 the inhibition of the respiratory center resulting in respiratory depression
 the inhibition of the tussive center resulting in a decrease of cough
 the inhibition of the vomiting center
 the inhibition of the thermoregulation center in hypothalamus
Uses:- Prophylaxis and treatment of pain shock, traumas, burns, acute myocardial
infarction, premedication for potentiating of action of drugs for general anesthesia,
analgesia in postoperative period, to relieve sufferings of oncology patients of 4th clinical
group (can’t be treated radically), acute abdomen (strong pain in abdominal cavity, caused
by perforation of ulcer, acute appendicitis, acute intestinal impassability etc.) –
shock, Myocardial infarction (together with atropine), Colic (together with atropine), Pain
associated with cancer, Pain after surgeries, Pre-anesthetic medica;on, Pulmonary edema.
Side-effects:- euphoria , sleeping , depression of respiraton, hypotension, constipation, drug
dependence, tolerance, evaluation of intracranial pressure
(Moa: Opoid analgesics stimulates all the types of opioid receptors. It has high affinity for
μ-receptors and some action for other opioid recep-tors In such a way it suppresses
neurotransmission in the nociceptive system that results in the rising of pain threshold in
the spinal cord and altering of the brain perception of pain.)

21b. Morphine: pharmacokinetics, pharmacodynamics, mechanism of action and

therapeutic use.
Morphine is an alkaloid of opium.
Pharmacokinetics
 is administered orally, SC, IM, IV, epidurally, intrathecally in the spinal cord
penetrates the blood-brain barrier
 is metabolized in the liver by conjugation with the glucuronic acid
 is the inhibitor of the liver enzymes
is excreted by gastric epithelium and absorbed once more

 finally is excreted with urine

 begins to act in 10-20 min after the injection or 20-30 min after the oral
administration acts during 3-5 hrs.

Pharmacodynamics
 analgesia (a decrease in all the kinds of pain; changes in perception of pain –
sensation of pain is not unpleasant)
 euphoria (sense of well being), then sleep sedation
 potentiation of other drugs inhibiting CNS
 the inhibition of the respiratory center resulting in respiratory depression the
inhibition of the tussive center resulting in a decrease of cough
 the inhibition of the vomiting center
 the inhibition of the thermoregulation center in hypothalamus
 the stimulation of the n. vagus center resulting in bradycardia
 the stimulation of the trigger zone of the emetic reflex that leads to vomiting in
some patients after the 1st administration of morphine
 the stimulation of the n. oculomotorius center resulting in miosis
 the stimulation of vasopressin production
 the dilation of peripheral veins
 an increase in the tone of sphincters in the GI tract, bile and urinary pathways
  an increase in the tone of bronchi

Mechanism of action
- morphine stimulates the all type of opoid receptors
- It has high affinity for μ-receptors and some action for other opioid receptors. In such a
way it suppresses neurotransmission in the nociceptive system that results in the rising of
pain threshold in the spinal cord and altering of the brain perception of pain
-Morphine also acts at κ receptors in lamina I and II of the dorsal horn of the spinal cord. It
decreases the release of substance P, which modulates pain perception in the spinal cord.
Morphine also appears to inhibit the release of many excitatory transmitters from nerve
terminals carrying nociceptive (painful) stimuli.
Use:- Traumatic shock, Myocardial infarction (together with atropine), Colic (together with
atropine), Pain associated with cancer, Pain after surgeries, Preanesthetic medication,
Pulmonary edema, Cough dangerous for life (the danger of pulmonary bleeding or pneumo-
thorax).
Side-effects :- Depression of respiration, Sleeping, Euphoria,
Vomiting,hypertension,constipation , Elevation of intracranial pressure, Tolerance (to the
respiratory depressant, anal-gesic, euphoric and sedative effects).

(Contraindications :- Insufficience of respiration , Cranial trauma, Acute abdomen , Cachexia,

Children till 3 (due to the higher sensitivity of the respiratory center to morphine in such pa- tients)

Elderly patients after 65 years old (due to an increased sensitivity of the respiratory center to mor- phine.

22b. Non-opioid analgesics: classification, pharmacodynamics, use and side effects.Acc. To

Mechanism of action –
1. Selective inhibitor of COX – 1 – Indomethacin, Piroxicam, Aspirin in small dose
(weakly selective)
2. Selective inhibitors of COX-2 – Celecoxib(highly selective), Meloxicam(dominant
influence), Rofecoxib.
3. According to the chemical structure
Salicylates– Acetylsalicylic acid (Aspirin)
Pyrazoles: Metamizole (Analgin), Phenylbutazone (Butadione)
*Fenamates: Mefenamic acid
*Indolacetic acid derivatives: Indomethacin
Phenylacetic acid derivatives: Diclofenac-sodium
*Propionic acid derivatives: Ibuprofen
*Para-aminophenol derivatives: Paracetamol (Acetominophen)
* Oxicams: Piroxicam, Meloxicam (Movalis)
Coxibs: Celecoxib
 4. Non-selective inhibitors of COX-1 and COX-2 –
(i) With peripheral action – Aspirin, Indomethacin, Ibuprofen, Diclofenac
sodium, Piroxicam, Metamizole, Phenylbutazone
(ii) With central action – Paracetamol.

1. Non-selective inhibitors of COX-1 and COX-2 Cyclooxygenase

A. Peripheral action
(i) Acetylsalycylic acid (aspirin):
Pharmacodynamics : anti-inflammatory, anti-pyretic, analgesic, anti-platelet, anti-
gout,stimulate respiration, dilation of blood vessels, stimulate synthesis of
glucocorticoids, increase secretion and excretion of bile, hypoglycemia.

Indication: Rheumatism, fever, arthritis, headache, toothache, myalgia, neuralgia, gout,

dysmenorrhea, prophylaxis of re-thrombosis, myocardial infarction or insult,
thrombophlebitis, patent ductus arteriosus.
Side effects: allergy, skin rash, spasm of bronchi, gastric ulceration, vertigo,
thrombocytopenia, hypocoagulation, bleeding. Bleeding tendency in mother and infant.
Contraindicated in children who recently have viral infections(due to increase tendency of appearance of reye’s syndrome.

Aspirin + Antacids = Decrease

aspirin’s absorption
Aspirin + Sulfinpyrazone, probenecid = decrease urateexcretion
Aspirin + Heparin, oral anticoagulants = hemorrhage Aspirin + Barbiturates,

(ii)Indomethacin:

pharmacodynamic : anti-inflammatory, analgesia, antipyretic.

Indication : rheumatism, collagenosis, arthritis, gout, glomerulonephritis, trauma of joints

and soft tissues, thrombophlebitis, tendovaginitis, myositis, myalgia, neuralgia, ductus
arteriosus.

Side effects : vertigo, dormancy, depression, pain in epigastric area, ulcer of stomach,
nausea, decrease appetite, GIT bleeding, leukopenia, skin rash, aplastic anemia, disturbance
in renal function, acute pancreatitis, hepatitis, jaundice.
(iii) Diclofenac- sodium : indication similar to indomethacin also including rheumatoid
arthritis, osteoarthritis and ankylosing spondylitis. Less toxic then indomethacin but may
cause pain in epigastric region, meteorism, constipation, diarrhea, GIT bleeding, headache,
drowsiness, nasal bleeding, microhematuria, allergy, skin rash.

(iv)Ibuprofen : anti-inflammatory and analgesic action. Not toxic, minimal influence on

gastric mucosa Ibuprofen is a non-selective inhibitor of an enzyme called cyclooxygenase
(COX), which is required for the synthesis of prostaglandins via the arachidonic
acid pathway
feeling and being sick (nausea and vomiting)
stomach pain.
feeling tired or sleepy.
black poo and blood in your vomit – a sign of bleeding in your stomach.
ringing in your ears (tinnitus)

(v)Piroxicam : anti-inflammatory. May cause ulcer, skin rash, toxic to CNS.

B. Central action
(i) Paracetamol Acetaminophen: intermediate analgesic and anti-pyretic activity, weak
anti-inflammatory action. Used in headache, muscle and joint pain, fever associated with
infection and inflammatory diseases. Analgesic-antipyretic of choice in children with viral
infections or chicken pox. Antidode- acetylcystin

2. Selective inhibitor COX-2

-Meloxicam: preferential COX-2 inhibitor
Use: osteo & rheumatoid arthritis

-Celecoxib : a selective COX-2 inhibitor, is significantly more selective for inhibition of COX.
The inhibition of COX-2 is reversible.

Used in rheumatoid arthritis, osteoarthritis may cause pain in epigastrium, stomach ulcer,
GIT bleeding, headache, vertigo, insomnia, depression, increase intracranial pressure,
hypertension

Adverse effects: Headache, dyspepsia, diarrhea, and abdominal pain are the most common
adverse effects.

23b. Ethyl alcohol, pharmacodynamics and use in medical practice.

it is applied topically, IV, orally. After oral administration it is absorbed easily.

Pharmacodynamics:

1. Local action: antiseptic action; disinfective action; irritating effect; tannic effect;
antifoam action
2. Resorptive action: anxiolytic action; antishock effect; stimulation of energy metabolism;
increase BP; antidote action; diuretic action; changes in gastric secretion

Using in medical practice

- The processing of surgeon's hands and the surgical
area(70%);
- the processing of instruments(95%);
- the inhalation in the mixture with oxygen in pulmonaryedema;
shock(20%,IV);
- cachexia/20%,IV);
- acute poisoning with methanol(20%,IV) { DOC: FOMEPIZOLE}
- producing sclerosis in the varicose veins (70%,inside
thepathological vein);
- alcoholizing of nerves (inside the nerve at the surgery).
24b. Anti-epileptic drugs: classification, pharmacodynamics, mechanism of action, use and side
effects.
Classification:
1. Preparations for the treatment of epilepsy with grand mal (convulsive/tonic clonic)–long
epilepsy seziure
- phenobarbital, phenytoin (diphenine), carbamazepine(finlepsin), valproic acid, sodium
valproate, clonazepam, lamotrigine.

2. Preparation for the treatment of epilepsy with petit mal – short epileptic seziure
– Valproic acid – Clonazepam – Lamotrigine
– Valproic acid and divalproex sodium: mechanisms of action include sodium channel
blockade, blockade of GABA transaminase, and action at the T-type calcium channels.

Carbamazepine
Carbamazepine blocks sodium channels, thereby inhibiting the generation of repetitive
action potentials in the epileptic focus and preventing their spread.

Carbamazepine is effective for treatment of focal seizures and, additionally generalized tonic–
clonic seizures, trigeminal neuralgia, and bipolar disorder.

Carbamazepine is absorbed slowly and erratically following oral

Pharmacodynamics : anticonvulsant effect;

Mechanism of action :

-phenytoin , phenobarbital and lamotrigine inhibit release of glutamate.

is used in epilepsy with grand mal, tachyarrhythmia (especially in acute poisoning with
cardiac glycosides), Menier’s disease

-benzodiazepins and phenobarbital increase inhibition by release of physiological amount of

GABA and its interaction with GABA receptors of chloride channels.
-valproic acid decreases GABA catabolism by inhibition of GABA transaminase.

-other preparations realize their action by antagonism to glutamate, a direct GABA mimetic
action, regulation of GABA reuptake.

Side effects :nausea, vomiting, drowiness, ataxia, rash, hyponatremia, weight gain or weight
loss, depression, tolerance, teratogenicity, weakness, dyspepsia, decrease blood coagulation,
life threatening skin reactions, loss of balance, vision disturbances, insomia, anxiety,
dysmenorrhea.

25b. Drug treatment of Parkinson’s disease and Parkinson’s syndrome, its side effects.
1. Drugs affecting brain dopaminergic system:
(a) Dopamine precursor: Levodopa;
(b) Peripheral decarboxylase inhibitors: Carbidopa, Benserazide;
(c) Dopaminergic agonists: Bromocriptine, Ropinirole, Pramipexole;
(d) MAO-B inhibitor: Selegiline, Rasagiline;
(e) COMT inhibitors: Entacapone, Tolcapone;

2. Drugs affecting brain cholinergic system:

(a) Central anticholinergics: Trihexyphenidyl, Procyclidine, Biperiden;
(b) Antihistaminics: Orphenadrine, Promethazine.

Pharmacodynamics: Dopamine receptor agonists binds to receptors on DAergic neurons, in

the absence of neurotransmitter. Stimulation of these receptors increases the DAergic
activity in the brain, lessening the severity of the symptoms.
Peripherally formed dopamine can cause tachycardia by acting on beta-adrenergicreceptors.
They have produce a awakening effect in hepatic coma.

Side effects: dyspepsia, orthostatic hypotension, arrhythmia, psychic disturbances, syncope,

angina pectoris, bradycardia

 Difference:
Vascular parkinsonism is caused by one or more small strokes, while Parkinson’s is caused by a
gradual loss of nerve cells.
One major difference from Parkinson’s is that it’s not progressive, while Parkinson’s becomes worse
with time. Another difference is that there are no tremors in vascular parkinsonism.
26b. Antipsychotics: classification, pharmacodynamics, mechanism of action, use and side
effects.
Neuroleptics also known As antipsychotics(used to treat psychosis)
Classification
1. Typical neuroleptics(first generation)
(i) Phenothiazines : Chlorpromazine (aminazine), trifluoperazine (triftazin), flunazine
(phtorphenazin)

(ii) Butyrophenones : haloperidol, droperidol

(iii)Thioxanthenes : chlorprothixene

2. Atypical neuroleptics(second generation)

(i) Dibenxzodiazepine : clozapine

(ii) Benzamides : Sulpiride

(iii)Benzisoxazoles : Risperidone

Pharmacodynamics : antpsychotic action; anxiolytic action; sedative action; ahypnotic

action; decrease psychomotor excitement; antiseizure action; antiemetic action;
antihypertensive action;potentiative action; hypothermic action; weak antiinflammatory and
antiallergic actions.
Mechanism of action : typical neuroleptics block D2-D1-D3-D4 dopamine receptors and
causes extrapyramidal distrbances.
Atypical neuroleptics block 5-HT2 receptors, alpha 2 adrenoreceptors, D4 dopamine
receptors and have a weak action on dopamine receptors, do not cause extrapyramidal
disturbance.
Uses :psychosis, shizophrenia, psychomotor excitement, seizures attacks, severe vomiting,
hypertensive crisis, hyperthermia, skin diseases accompanied by itching, hibernation,
hyperthermia;

Side effects : irritation in the place of injection, pain in the stomach,irritation of the skin and
mucous membranes, confusion, blurred vision, dry mouth, hyposecretion in the stomach,
constipation, urinary retention, hypotension, liver lesions, icterus, dermatitis, phototoxicity,
inhibition of hemopoiesis(leukopenia, agranulocytosis),parkinsonian symptoms(tardive
dyskinesia, akathisia),neuroleptic syndrome(apathy,
depression, parkinsonism)

27b. Tranquilizers: drugs, pharmacodynamics, mechanism of action, use and side effects.
A tranquilizer refers to a drug which is designed for the treatment of anxiety, fear, tension,
agitation, and disturbances of the mind, specifically to reduce states of anxiety and tension.

Classification

1. Benzodiazepines – chlordiazepoxide (Cholespide),

Diazepam(Sibason),Medazepam, ,Phenazepam;

2. other preparations - Buspirone,Meprobamate,Benactyzime;

according to duration
drugs of long lasting action- diazepam, phenazepam, clozepid
drugs of medium lasting action- lorazepam, alprazolam
drugs of short lasting action- medazolam

Pharmacodynamics : anxiolityc action(decrease stress,anxiety and panic); sedative action;

hypnotic action; antiseizures action; potentiative action; central myorelaxative action.

Mechanism of action :benzodiazepines bind to their receptors of chloride ion channel and
open them,thus chloride entry is increased that leads to hyperpolarization of cell
membranes. Then decreasing neurons excitement in the lymbic system,midbrain;

Using : neuroses,stress, emotional overstrain,sleeping disorders, seizures,psychosomatic

diseases,abstinence in chronic alcholics;

Side effects : weakness, drowsiness, ataxia, skin itch, impotence, amenorrhea, drug
addiction, drug dependence.

28b. Hypnotics: drugs, their pharmacodynamics, mechanism of action, use and side
effects.
Hypnotics are the drugs for the treatment of insomnia. They induce the onset of
sleep and maintain it.

Classification:
Barbiturates – Phenobarbital – Barbital – Ethaminal (Aethaminalum-natrium)
Benzodiazepines – Nitrazepam
Aliphatic compounds – Chloral hydrate
Other preparations – Donormyl – Zopiclone – Zaleplon.

PHENOBARBITAL: derivative of the barbituric acid . The substance is not soluble in

water, but solubility is increased in alkalic pH.
P.D: a hypnotic action with the change in normal sleep structure (inhibition of REM-
sleep) a sedative action, an anti-epileptic action the potentiation of the effect of
other drugs inhibiting CNS.
P.K: Pharmacokinetics is taken orally, is absorbed in the small intestine is strongly
bound to proteins in plasma
penetrates CNS and placenta is metabolized in microsomes of the liver is the
inductor of microsomal oxidation
excreted with urine is accumulated (material accumulation) starts to act in 30-60 min
after the administration and acts during 6-8 hrs, stays in the body during 1-2 days.
M.O.A: binds to barbiturate receptors of chloride channels. That results in
enhancement of GABAA-receptors’ activation and opening of chloride channels. An
increase in the Cl- influx leads to the membrane hyperpolarization, difficult
depolarization, and the inhibition of neuron function.
Use: Insomnia, Epilepsy with grand mal, Icterus in newborns, & As the ingredient of
combined sedative and analgesic preparations
C.I: Liver and renal diseases, hypotension, intermitted purpura, age about 60 or till 10
years old, pregnancy. The drug should not be used in patients whose job needs quick
motor reaction, as well as for long treatment

Side-effects: weakness, drowsiness, apathy, slow motor reaction in the morning,

drug dependence, The suppression of respiration, Hypotension, Liver lesions.

Nitrazepam is a benzodiazepine derivative; is the agonist of benzodiazepine

receptors of Cl- ion channels; has a hypnotic action with minimal changes in the
normal sleeping structure; has anxiolytic, sedative, central myorelaxative and
potentiative effects; is used in insomnia, neurosis, epilepsy, abstinence in alcoholics;
has less side-effects than phenobarbital (less tolerance, drug dependence, and return
syndrome); does not produce the activation of liver enzymes.

Chloral hydrate is administered orally or rectally; is converted to trichlore

tha-nol; has an anti-seizure and sedative action; is applied in seizures, insomnia, and
severe cough in children; irritates mucous membranes (is used with the addition of
starch mucus).

Donormyl is H1-histamine blocker from the group of ethanolamines. The drug has a
hypnotic, sedative and M-anticholinergic action. Reduces the time of falling asleep,
increases the duration and quality of sleep, while not changing the phase of sleep.
The duration of action is 6-8 hours.

Zopiclone is cyclopirrolone derivative, which interacts with ω1- and ω2 –

(omega 1&2) benzodiazepine receptors of the macromolecular GABA-
benzodiazepine-chloronophore complex. The drug shortens the period of falling
asleep, reduces the number of nocturnal awakenings, improves the quality of sleep,
does not change the phase structure of sleep. It is effective in situational insomnia,
changes in the usual rhythm of life, and a shift work regime. Sleep occurs within 20-
30 min and lasts 6-8 hours. Side effects are drowsiness, lethargy, headache, dizziness,
irritability, confusion, muscle weakness, impaired coordination of movements,
diplopia, memory impairment, paradoxal reactions. Addiction, drug dependence, and
withdrawal syndrome also are possible.

Zaleplon is derivative of pyrazolopyrimidine, which selectively binds to ω0 -

benzodiazepine receptors and excites them, that leads to the opening of chlorine
channels, hyperpolarization, and inhibition in the CNS. It reduces the latent time of
falling asleep, prolongs the sleep time in the first half of the night, does not change
the ratio of the sleep phases. Doses of 5-10 mg do not cause tolerance at 2- 4 weeks.
The drug has sedative, weak anxiolytic and central myorelaxant effect. Indications to
use are short-term treatment of severe forms of sleep disorders (difficulty falling
asleep), disturbing day activity. The most common undesirable effects are memory
impairment, paresthesia, drowsiness and dysmenorrhea.
29b. Sedative agents: drugs, their pharmacodynamics, mechanism of action, use and side
effects.
Classification –
1. non – organic preparations – sodium bromide, potassium bromide.
2. vegetative preparations – tincture from valerian, tincture from leovnurum.
3. metabolic sedatives – melatonin, glicised.
4. combined preparations – corvalol, valocormidum, persen, novo-passit.

Pharmacodynamics – Sodium bromide has sedative action, hypnotic action, anti-epileptic

action.
Vegetative preparations has sedative, hypnotic, spasmolytic action.
Melatonin has anti-oxidant action, glycised has mild sedative, anti-anxiety, nootropic, anti-
toxic action.
Combined preparations has sedative, spasmolytic, light hypnotic, anxiolytic action.

Mechanism of action – sodium bromide increases inhibition in CNS, effective dose depends
on the type of higher nervous activity.
Melatonin regulates circadian rhythms through activation of melatonin receptors. Glycised
has amino acid glycine which participates in neurotransmission in glycinergic and GABA-
ergic synapses.

Uses –
 sodium bromide used in light neuroses, neurasthenia, hysteria, restlessness,
insomnia, epilepsy, light forms of hypertension.
 Vegetative preparations used in cardioneurosis, somatic disease with neurotic
syndrome, spasms of stomach and intestine.

 Melatonin used in jet lag and shift work, headaches, protection from radiation.
Glycised used in neurocirculatory dystonia, alcohol abstinence, sleep disorders,
depression, increased irritability.

 Novo-passit(combined prep) used in climacteric syndrome, functional diseases of GI

tract.

Side effects – drowsiness, skin rash, rhinitis, cough, apathy, weakness,

memorydisturbances.

30b. Psychostimulatory drugs: pharmacodynamics, mechanism of action, use and side

effects.
Are the drugs stimulating mainly cortical part of CNS.
Pharmacodynamics:

 A psychostimulant action, an analeptic action,

 the stimulation of reflexive activity of the spinal cord,
 changes of heart rate, which depend on the ratio between a direct action on the
heart and an indirect one resulting from the stimulation of the center of n.vagus,
 action on blood vessels, blood vessels in the heart, lungs, kidney, skeletal muscles
are dilated;
 blood vessels in the brain are dilated from the first, then – constricted, the elevation
of BP, the stimulation of gastric secretion, a diuretic action.
Mechanism of action:
They blocks the subtypes of adenosine receptors and decreases their inhibiting influence in
the brain.
In such a way it increases excitement in the brain cortex and some other areas of CNS. They
stimulates the translocation of extracellular calcium into cells.
It inhibits phosphodiesterase and increases cAMP concentration in cells. The drug also
increases the activity of phosphorylase resulting in an increase of glycogen metabolism and
forming of the energy.
Uses: For an increase of mental and physical capacity to work, asthenia, fatigue, hypotention,
collapse, the suppression of respiration, headache.
Side-effects: anxiety, insomnia, irritability, weakness, tremor, confusion, delirium, panic state,
anorexia, hypertension, tachycardia, arrhythmia, tolerance, addition, psychic and physical
dependence.

31b. Analeptics: drugs, their pharmacodynamics, mechanism of action, use and side
effects.
Analeptics are the drugs which stimulate mainly the respiratory and vasomotor centers in
medullar part of CNS.
They have such effects as:
- an increase in respiration resulting from the stimulation of the respiratory center
- an increase in BP resulting from the stimulation of vasomotor center
- a decrease in the action of drugs inhibiting CNS (an awakening effect) seizures (in
higher doses)

CLASSIFICATION:
according to type of action:

1. direct-acting analeptics: (Caffeine, strychnine, etimizol, Bemegride):stimulate

respiratory and vasomotor centers directly;

2. indirect-acting analeptics: (Lobeline, Cytizin): provide the reflex stimulation of the

respiratory center via chemoreceptors of the carotid sinus;
 3. mixed-acting analeptics:- (Camphor, Carbonic acid, Nikethamide [cordiaminum],
carbogen,sulfocamphocaine): provide the reflex action through the chemoreceptors
of vessels together with the direct action on the vitally centers of the medulla
oblongata.

According to mechanism of action –

1.membranetropic – camphor, sulfocamphocaine.
2.barbituratergic- bemegride
3.benzodiazepinergic- nikethamide
4.purinergic- caffeine, etimizol
5.glycinergic- strychnine.

MECHANISM OF ACTION
If we talk about Camphor, is a mixed-acting analeptic. It has a direct and indirect action.
Direct action includes disturbances in the permeability of the neuronal membrane to Na+.
They results in an increase of Na+ concentration in the cells that leads to the maintenance
of the excitement of neurons in the medulla of brain.
The indirect component of camphor’s mechanism of action is realized by the stimulation of
chemoreceptors of zona carotis and a reflexive excitation of centers in the prolonged
medulla
PHARMACODYNAMICS
- the stimulation of the respiratory center in its moderate suppression resulting in
the acceleration and deepening of breath
- the stimulation of the vasomotor center in its suppression resulting in an
increase of BP
- an awakening action and a decrease in the effects of CNS inhibitors
- a positive inotropic action (an increase in strength of heart contractions under
the conditions of heart failure resulting from the enhance of the myocardium
sensitivity to catecholamines and the intensification of metabolic processes)
- the improvement of microcirculation
- the inhibition of platelet aggregation
- an expectorant action resulting from excretion by bronchial glands
- the stimulation of lactation.

USES:

- A moderate suppression of respiration caused by infections and intoxications

- Collapse, shock Acute and chronic heart failure
- Pneumonia
- Skin diseases, external otitis, myalgia, myositis, arthralgia, arthritis, for the prophylaxis of
trophic disturbances of the skin in long lying patients (topically).
SIDE EFFECTS: Allergy, seizures, infiltration at site of injection, Fat embolism if the drug is administered IV/.IM

Contraindication: Should not be administered IV/IM; Hypersensitivity (to camphor), Epilepsy (prone to
seizures),

Sulfacamphocaine is a complex compound of camphor and procaine; is water-soluble; is

administered SC, IM, IV; is not applied topically;
used for the suppression of respiration, collapse, shock, overdose of drugs inhibiting CNS,
heart failure; is contraindicated to patients with allergy to procaine.

Nikethamide (Cordiaminum) is a commercial name of 25% solution of diethylamide of the

nicotinic acid; is administered IV, IM, SC, orally; has a short action; is a mixed-acting analeptic
(its direct action results from the inhibition of benzodiazepine receptors of Cl- channels); has
typical analeptic effects; improves metabolism in the heart and liver; is indicated in the
suppression of respiration, collapse, shock, overdose of CNS inhibitors, chronic heart failure
(orally); may cause seizures, hyperemia of the skin, pain in the site of injection; is
contraindicated to patients with epilepsy, psychic excitement, hypersensitivity to the
nicotinic acid.

Bemegride is a synthetic preparation, a derivative of piperidine; is administered IV; is not

bound to plasma proteins and begins to act quickly; is widely distributed in the body; is
metabolized in the liver and excreted with urine; is a strong direct-acting analeptic inhibiting
barbiturate receptors of Cl- ion channels; an awakening action is the strongest effect in
comparison with other effects of Bemegride (by this action Bemegridum is more potent than
other analeptics); is indicated in acute poisonings with barbiturates, alcohol, narcotic
analgesics; overdose of general anesthetics; suppression of respiration; may cause seizures,
tremor, hyperventilation, arrhythmia; is contraindicated in epilepsy, psychomotor
excitement, intoxication with seizure poisonings.

Etimizol is a synthetic preparation, an imidazole derivative; is administered IV, IM, and orally;
has short action; is a direct-acting analeptic inhibiting adenosine receptors; decreases
phosphodiesterase activity, thus increases cAMP in cells;
has pharmacological effects, which by their strength form the line: the stimulation of the
respiratory center; the stimulation of vasomotor center and awakening action; produces the
stimulation of ACTH secretion resulting in anti-inflammatory and anti-allergic effects, displays
cognitive enhance, the improvement of the tone of myocardium and skeletal muscles, dilates
bronchi; increases surfactant synthesis in the lungs; is used in the suppression of respiration,
asphyxia of newborns, the prophylaxis of lungs atelectasis during inhalation general
anesthesia, bronchial asthma, pneumonia, rheumatoid arthritis; may cause dyspepsia,
vertigo, restlessness, insomnia; is contraindicated in epilepsy, psychic disorders, excitement.

Strychnine is an alkaloid of vomiting nut; is administered SC and orally; is direct-acting drug

inhibiting glycine receptors; acts mainly on the spinal cord, stimulates reflexive activity of the
spinal cord; stimulates the cortex parts of analyzers, especially a vision analyzer; is used in
neurological diseases accompanied by hypotonia, paralysis, paresis, asthenia, disturbances of
vision resulting from encephalitis, atonia of the GI tract and urinary bladder, impotence; is
used very rarely due to high toxicity:
is a seizure poison (Seizures caused by strychnine are treated by myorelaxants).

Carbogen is a mixture of 3-7% CO2 and 93-97% O2; is administered by inhalation; has a
mixed action; is a physiological stimulant of the respiratory center; is used for the treatment
 of asphyxia, respiratory arrest, prophylaxis of atelectasis and pneumonia after inhalation
general anesthesia, suppression of respiration; may cause suppression of breathing if
concentrations of CO2 will be high.

32a. Antidepressants: drugs, their pharmacodynamics, mechanism of action, use & side effects.

Antidepressants are the drugs for the treatment of depression.

CLASSIFICATION OF ANTI-DEPRESSENT DRUGS

 According to the mechanism of action

A. Inhibitors of monoamine re-uptake

Non-selective inhibitors of the monoamine re-uptake (inhibit reuptake of both serotonin & NE.)

– Imipramine (Imizinum)

– Amitriptyline

Selective inhibitors of the serotonin re-uptake; SSRIs(by blocking serotonin transporter= >>serotonin
in postsynaptic receptors)

– Fluoxetine, Sertraline

Selective inhibitors of the norepinephrine re-uptake; SNRIs (by blocking serotonin & NE transporter=
>>serotonin & NE)

– Maprotiline

B. MAO inhibitors

(inhibits MAO enzyme that degrades monoamines such as serotonin & NE, ultimately increasing their
bioavailability.)

{MAO-A; deaminates 5HT & NA.}

{MAO-B: deaminates phenylethylamine {neurotransmitter involved in passionate love }

(inhibited by SELENGILINE)}

Non-selective (MAO-A and MAO-B):

Phenelzine & Tranylcypromine (irreversible), Nialamide

Selective (MAO-A):

– Pirlindole (Pirazidolum)
– Moclobemide (reversible)

C. Atypical antidepressants:

– Trazodone (inhibit serotonin reuptake as well as block postsynaptic serotonin receptor of

5-HT2A)

– Minaserin (block presynaptic alfa receptors, increasing NE release in brain.)

Antagonist of: 5-HT2, 5-HT1c, & H1 receptors

 – Agomelatine (melatonergic agonist MT1 & MT2 receptors and 5-HT2 antagonist)

– Ademetionine, & St. John’s wart

 According to the additional action

A. Thymoleptics (+ a sedative effect) – Amitriptyline

B. Thymoerectics (+ a psychostimulating effect) – Nialamide (RESERINE antagonist)

C. Mixed acting – Imipramine – Pirlindole.

Pharmacodynamics
- an anti-depressive action
- a thymoleptic {mood modifying} action in the emotional sphere (a sedative or
weak psychostimulantaction)
- the absence of CNS stimulation or mood elevation in normal individuals
- a peripheral M-cholinoblocking action an antihistamine action.

Mechanism of action:
If we talk about Imipramine, the mechanism of action includes the inhibition of the
norepinephrine re-uptake resulting in an increase of adrenergic processes in brain
structures.

It is also connected with the inhibition of the serotonin re-uptake resulting in an increase of
the serotonin amount in synapses that leads to an increase in serotonin inhibiting influence
in the limbic system.

Imipramine and other tri-cyclic antidepressants block central and peripheral M-

cholinoreceptors. A sedative and antimuscarinic action is due to such blockade. It also
blocks α-adrenergic receptors and histamine receptors.

Uses: severe major depression, reactive depression, parkinsonism, schizophrenia, stroke,

tumors, alcoholism, senile psychosis, atherosclerosis of brain, post-traumatic states.

Side effects: excitement, insomnia, headache, tremor, tachycardia, arrythmias, allergy, dry
mouth, vomiting, drowsiness, dizziness, hallucination, agitation, lowering of BP, nausea,
hepatotoxicity, nephrotoxicity.
- Acute attacks of epilepsy
- Cardiotoxic action (sudden death),
- tri-cyclic antidepressants increase arrhythmogenicactivity of drugs for general
anesthesia, antihistamines etc.

- Combination of tri-cyclic antidepressants with IMAO is absolutely contraindicated: danger

of development of hypertensive crisis, seizures, rapid excitation, tachycardia, cardiac
arrhythmias, increasing of temperature.
33b. Cardiac and extra cardiac effects of cardiac glycosides.
Cardiac action: increase myocardial contractility & output without increasing oxygen
demand.

Digitalis has direct and indirect actions on the heart.

■ Direct action by inhibiting Na K+-ATPase

■ Indirect action by stimulating vagus (vagomimetic effect)

Myocardial contractility: Digitalis increases the force of contraction of the myocardium

(positive inotropic effect). This effect is more prominent in the failing heart.

Digitalized heart contracts more forcibly and completely. The positive inotropic effect
causes complete emptying of the ventricles during systole and increases the CO. The
diastolic size of the heart is reduced.

When the size of the heart is reduced, muscle fiber length is also reduced, thereby,
decreasing the oxygen requirement of myocardium. The digitalized heart, thus, can do more
work for the same energy. Therefore, digitalis is called a 'cardiotonic.

Heart rate: In patients with CCF, digitalis reduces the heart rate (negative chronotropic
effect) by direct and indirect actions. In small doses, digitalis decreases heart rate by
stimulation of vagus. In toxic doses, it can increase sympathetic activity thus increasing
heart rate.

Electrophysiological actions: At therapeutic concentrations, digoxin decreases automaticity

and increases resting membrane potential by vagal action in atria and AV node. It also
prolongs ERP and decreases conduction velocity in AV node.

This may lead to bradycardia and AV block. At higher concentrations, digoxin can increase
automaticity in cardiac tissue by direct action as well as by increasing sympathetic activity.
This can result in atrial and ventricular arrhythmias.

ECG: Digitalis produces prolongation of P-R interval, inversion of T wave and depression of
ST segment.

-positive inotropic effect (increase in the force of contraction, increase in the myocardial tone);
-negative chronotropic effect (prolongation of diastole, slowing of HR);
-negative dromotropic effect (deceleration of conductivity);
-positive bathmotropic effect (increase in myocardium excitation);

Extracardiac action:
- improve blood circulation;
- decrease in venous pressure, normalization of arterial blood pressure;
- increase in renal blood flow, which leads to an increase in diuresis and decrease in
edema
- Sedative
- Gastrointestinal tract (GIT): Digitalis can produce anorexia, nausea, vomiting and
 occasionally diarrhea.
- Nausea and vomiting are due to stimulation of chemoreceptor trigger zone (CTZ) and
a direct action on the gut.
- Central nervous system (CNS): In high doses, it can cause central sympathetic
stimulation, confusion, blurring of vision, disorientation, etc.

Common side affects:

Anorexia, nausea, and vomiting may be initial indicators of toxicity.

Patients may also experience blurred vision, yellowish vision (xanthopsia), disorientation,
psychosis, mental confusion, fatigue,

arrhythmia (tachyarrhythmia-cure by KCl solution, supraventricular-cure by

propanalol,ventricular-lidocaine,)

34b. Symptoms and principles of treatment of cardiac glycosides intoxication, its

prophylaxis.
Acute poisoning with cardiac glycosides
Signs:

 bradycardia, then tachycardia and arrhythmia (premature ventricular beats,

fibrillation);
 changes in ECG;
 an increase in signs of CHF;
 anorexia, vomiting, nausea,headache, fatigue,
 hallucination
 vision disturbances (xanthopsia, micro- and macropsia).

Emergency help:
 The abolishing of cardiac glycoside
 Drugs containing potassium (potassium chloride, panangin)
 SH-group donator (dimercaprol, or unithiol)
 Anti-arrhythmic agents (phenytoin, lidocaine, propranolol, an atropine for AV block)
 Digoxin antibodies (digibind)
 Glucose, vitamins preparations, oxygen inhalation.

Prophylaxis – potassium preparation must be administered.

35b. Non-glycosides inotropic drugs, their pharmacodynamics, mechanism of action, use

and side effects.
Classification:
1. Adrenomimetics: Dobutamine (selective B1 agonist), Dopamine (B1 agonist), Isoprenaline
(B1 & B2 agonist), Ephedrine (alfa & Beta agonist);
2. Selective phosphodiesterase III (PDE III) inhibitors: Amrinone, Milrinone (more selective &
 10 times more potent);
3. Calcium sensitizers: Levosimendan (Simdax).
Mechanism of action: improves myocardial contractility (binding to cardiac troponin C),
decreases preload & afterload (without increasing O2 demand), vasodilation (increasing K+
intracellularly).
Use: in acutely decompensated severe CHF, (if conventional therapy is not sufficient)
patients with severe CO reduction (compromised vital organ perfusion)
Side-effects: headache, hypotension, arrhythmias, myocardial ischemia, hypokalemia &
nausea.

Pharmacodynamics: adrenomimetics has a positive inotropic action, improves coronary

circulation, reduces peripheral resistance, redistributes blood flow in favor of the heart and
lungs, increases the renal blood flow, does not act on heart rate; does not cause hypertension.
Side-effects: tachycardia, arrhythmia, hypotension, myocardial ischemia, hypokalemia,
nausea
Use: acute heart failure, cardiogenic shock.

Mechanism of action: PDE III) inhibitors

Increased force of contraction - activation of adenylate cyclase and increased cyclic AMP in
myocardial cell, transmembrane influx of ca2+ (phosphorylation of Ca2+ channel) and
increase the Ca entry.

Reduced preload and afterload - Direct inhibition of smooth muscle of arteries and veins.

Uses: only short term in severe refractory CHF & as an additional drug to conventional therapy
with Digitalis, Diuretics, Vasodilators.

Side-effects: nausea, vomiting, diarrhea, liver damage, fever, arrhythmias & thrombocytopenia
(transient & asymptomatic)

36b. Pharmacological characteristics and use of clonidine (clopheline) and methyldopa.

Clonidine is an α2 agonist that is used for the treatment of hypertension.

Clonidine acts centrally on presynaptic α2 receptors to produce inhibition of sympathetic

vasomotor centers, decreasing sympathetic outflow to the periphery (lowering BP).

Pharmacological properties:
-is administered sublingually, orally, IV, IM;
-is absorbed in the GIT;
-penetrates the CNS;
-is metabolized in the liver and excreted with urine;
-decrease BP, HR, Cardiac Output;
-sedation; decrease in pain; decrease Intra Ocular Pressure;
the potentiation of other drugs inhibiting CNS

Uses: chronic hypertension; hypertension crisis; glaucoma; migraine; pain syndromes; chronic
alcoholism; potentiation of general anesthesia, used to control opioids withdrawal symptoms
from alcohol & opioids, ADHD
Side effects: are lethargy, sedation, constipation, and xerostomia. Abrupt discontinuance
must be avoided to prevent rebound hypertension.

Methyldopa:
Pharmacological properties:
-is taken orally;
-is well absorbed by the GIT;
-penetrates the CNS;
-decreases the activity of vasomotor center, inhibits sympathetic impulsation to bloodvessels,
dilates blood vessels and lowers BP;
-has antihypertensive action, improves cerebral blood flow, increases lactation

Uses: hypertension
Side-effects: muscular and joint pains, a rise in the body temperature, skin rash, galactorrhea
Contraindication: to patients suffering from depression, Parkinson’s disease, liver diseases.

37b. Pharmacokinetics, mechanism of action and use of beta-blockers, side effects.

β-adrenoblockers are preparations which bind to β-adrenoceptors and prevent their
stimulation by norepinephrine (decreased sympathetic effect).
CLASSIFICATION

Non-selective: Propranolol (Anaprilin), Pindolol, Timolol (in glaucoma), Oxprenolol

Selective:
Metoprolol – Atenolol – Nebivolol – Bisoprolol

Mixed:
Labetalol, Carvedilol

Pharmacokinetics: is administered orally, IV, topically (eye drops); is absorbed in the GI tract;
binds to proteins in blood serum; penetrates CNS; is metabolized in the liver; is excreted with
urine; acts during 3-4 hrs.

MECHANISM OF ACTION
If we talk about propranolol, it blocks β1-adrenoceptors in the heart (lowers BP & decrease
cardiac output) and β2-adrenoceptors inother organs (blood vessels, bronchi, etc.). cardio
selective only affects beta 1,

also block β1-adrenoreceptors in the kidney and inhibit renin secretion resulting in a decrease
of peripheral resistance and blood volume.

Uses: migraine prophylaxis Hypertension, Ischemic heart disease, Supraventricular

tachyarrhythmia(propranolol),Hyperthyroidism, Migraine, Glaucoma.

Side-effects: Bradycardia, Hypotension, increasing of the heart incompetence, Heart block,

Spasm of bronchi, Hypoglycemia when insulin is given together with Propranolol, Fatigue,
Drowsiness, Vertigo, Depression.
38b. Pharmacodynamics, mechanism of action, use of Ca-channel blockers.
Calcium channel blockers (calcium antagonists) are preparations which block calcium
channels of L-type and cause an antianginal, anti-arrhythmic and anti-hypertensive action.
CLASSIFICATION

According to the chemical structure

Phenylalkylamines

– Verapamil

Dihydropyridines

– Nifedipine (Phenigidine)

– Amlodipine

Benzodiazepines

– Diltiazem

According to generations

The first generation – Verapamil – Nifedipine – Diltiazem

The second generation – Nifedipine retard

The third generation – Amlodipine.

MECHANIM OF ACTION
These drugs block voltage-gated “L-type” calcium channels and decrease Ca++ entry in the
cells of the myocardium and the smooth muscles of blood vessels (relaxation).

Reduction of intracellular calcium concentration leads to a decrease in the activation of

Ca++-ATP-ase, a decrease in phosphate utilization, deceleration of slow diastole
depolarization of membranes.
The result is a decrease in the contractility, excitability, and automaticity of myocardium,
relaxation of smooth muscles and dilation of blood vessels
-ve inotropic, chronotropic, dromotropic effects

PHARMACODYNAMICS

 the dilation of blood vessels, the reduction of total peripheral resistance,the

redistribution of blood in the body, a decrease in the load on the myocardium
resulting in a decrease of oxygen consumption
 the dilation of coronary arteries and arterioles resulting in an increase of oxygen
supply
 a decrease in AV and SA node conduction, the prolongation of the effective
refractory period within the AV node resulting in an anti-arrhythmic action
 the dilation of peripheral blood vessels resulting in a decrease of BP and an
antihypertensive action
 an anti-platelet action and a decrease in blood viscosity
 the relaxation of the smooth muscles of uterus, bronchi, and the gut.
Uses: Angina pectoris, Hypertension, Tachyarrhythmia.

Side effect - Verapamil and diltiazem should be avoided in patients with heart failure or
with atrioventricular block due to their negative inotropic (force of cardiac muscle
contraction) and dromotropic (velocity of conduction) effects. Dizziness, headache,
and a feeling of fatigue caused by a decrease in blood pressure are more frequent with
dihydropyridines

39b. Myotropic hypotensive drugs (natrium nitroprusside, magnesium sulphate,

appresin): pharmacodynamics, mechanism of action, use.
1. Sodium nitroprusside:

Pharmacodynamics: decreases BP; decreases the load of myocardium; increases Cardiac

Output under the condition of HF; increases the secretion of renin

Mechanism of action: n\Sodium nitroprusside breaks down in circulation to release nitric

oxide (NO). It does this by binding to oxyhemoglobin to release cyanide, methemoglobin
and nitric oxide. It binds to SH-groups of nitrate receptors, & activates guanylate cyclase in
vascular smooth muscle and increases intracellular production of cGMP lead to the
dephosphorylation of the myosin light chain and relaxation of vascular smooth muscles

Uses: hypertensive emergencies; AHF; edema of the lungs; controlled hypotension in

surgeries
Side-effects: hypotension, nausea, sweating, restlessness, retrosternal pain.

2. Magnesium sulphate:

Pharmacodynamics: has a sedative, hypnotic and narcosis action; has antiseizure

action, dilate blood vessels and decrease BP; has antiarrhythmic action, decrease IOP,
increase diuresis; is antidote in acute poisoning with compound containing calcium

Mechanism of action: is calcium channel blocker

Uses: in hypertensive emergency; chronic hypertension; seizure attack; edema of the brain;
tachyarrhythmia; Myocardial Infarction; toxicosis of pregnancy; overdose of calcium
preparations
Side-effects: pain and infiltrate in the site of administration (IM), suppression of respiration
(IV). If the suppression of respiration is occurred, calcium chloride (IV) and carbogen
(inhalation) should be used.

3. Apressin:

Pharmacodynamics: hypertensive action; increases HR and Cardiac Output; elevates

pressure in the lung artery; increases renin secretion

Mechanism of action: activates K channels, causes hyperpolarization and the blockade of

Ca channels, relaxes arteriolar smooth muscles and dilates arteriolar vessels;as a result,
decreases peripheral vascular resistance and decreases BP

Uses: moderate and severe hypertension; CHF

Side-effects: weakness, headache, tachycardia, worsen in angina, flushing of skin,
sweating, reversible lupus-like syndrome, retention of water and salts.

40b. Inhibitors of angiotensin-converting enzyme (ACE inhibitors): mechanism of action,

use, side-effects.
Drugs: Captopril, Enalapril, Lisinopril, Ramipril & Fosinopril (may be used in renal failure
patients because it is eliminated from both renal & hepatic pathways.)

Mechanism of action: they block ACE and disturb the transformation of angiotensin I to
angiotensin II. The result is the decrease of output of the sympathetic nervous
system, vasodilation, a decrease in sodium and water retention, enhance in the bradykinin
level in blood. They decrease afterload and preload causing increased cardiac output.

Pharmacodynamics-
 vasodilation caused by diminishing of angiotensin ΙΙ contents and an increase in
the bradykinin level in blood
 a decrease in the blood volume resulting from the inhibition of the secretion of
aldosterone and reducing of its action on sodium and water excretion
 a decrease in BP resulting from the vasodilatation and a decrease of blood volume
 a decrease in the load on the myocardium
 an increase in cardiac output under the conditions of heart failure
 a decrease in oxygen demand of the myocardium
 the reduction of pressure in blood vessels of the lungs

Uses: hypertension; chronic Congestive Heart Failure; Myocardial Infarction.

Side effects: skin rash; dry cough; fever; hypotension; hyperkalemia; disturbance in the
renalfunction, hypotension, altered taste(dysgeusia).

41b. Principles of drug therapy in hypertension .

- mild hypertension can be controlled with one drug.
- severe hypertension must be treated with the combination of drugs .
- drugs for the combined therapy of hypertension are selected to minimize the side-
effects of the combined regimen .

“First-line” drugs:

are diuretics: Furosemide LASIX, Hydrochlorothiazide

β-adrenoblockers: Acebutolol Atenolol Bisoprolol
ACE inhibitors: Benazepril Captopril Enalapril Fosinopril
Antagonists of angiotensin-II receptor: Losartan
calcium channel blockers: Amlodipine Diltiazem Felodipine
alfa-beta adrenoblockers: Labetolol Carvedilol
“Second line drugs:
α1-adrenoblockers: Doxazosin Prazosin Terazosin
α2-adrenoblockers: Clonidine & Methyldopa
vasodilator: nitroprusside and nitroglycerin, hydralazine
Sympatholytics: Reserpine & Octadin

“New drugs”
Imidazolines: Moxonidine, Rilmenidine
Serotonin receptor blockers: Ketanserin
Ca2+ antagonist & α2 adrenoblocker: Monateril

42b. Antianginal drugs: classification, pharmacokinetics, mechanism of action, use.

Classification:
1.Drugs that decrease oxygen demand of myocardium and increase oxygen supply:

-organic nitrates: Nitroglycerin(sublingual), Sustac (tablet), Isosorbide dinitrate(tablet, spray,

injection, sublingual), Isosorbide mononitrate;

-calcium channel blockers: Verapamil (oral), Nifedipine (oral, sublingual),Amlodipine(oral) ;

2.Drugs that decrease oxygen demand of myocardium only:

-beta-adrenoblockers- Propranolol (oral/IV), Metoprolol (oral/IV), Talinolol, Atenolol;

3.Drugs that increase oxygen supply only:

-substances of myotropic action: Dipyridamole (oral or IV), Papaverine(oral, IV, IM) ,

Drotaverine;

-substances of the reflexive mechanism of action: Validol

4. Drugs acting on myocardial metabolism: Sodium adenosine triphosphate, Trimetazidine,

Tocopherol acetate

sodium channel blocker- ranolazine

PHARMACODYNAMICS--
-antianginal effect: negative inotropic and chronotropic effects;
-decrease oxygen consumption by the myocardium and increase oxygen delivery;
-coronaro dilating effect provided by Coranorolytics (Dipyridamole, Carbocromen, Menthol);
-antiaggregant effect (Dipyridamole);
-improvement of the metabolism of the myocardium (Trimetazidine)

Mechanism of action:

-organic nitrates: increase in destruction of NO or insufficient formation of NO by the vessels'

endothelium, thus leading to calcium level decreasing in the cells, then coronary and
Peripheral vessels dilatation and heart's work decreasing;
-calcium channel blockers: block transmembrane flow of calcium into cardiomyocytes. Thus,
causing a decreasing in the heart's work with slowing its rhythm down, coronary and
peripheral arteries dilation as a result the myocardium needs less oxygen and its supply
increases;

-beta-adrenoblockers: block beta-adrenoreceptors thus causing a decreasing in heart's work;

-substances of the reflexive mechanism: dilates coronary vessels by reflex and increase the
oxygen supply to the myocardium by irritating the mouth mucous membrane receptors;
-drugs acting on myocardial metabolism: provide transmembrane transfer of Na, Ca, K
supporting the homeostasis in cardiomyocytes.
Uses: MI, recovering therapy after MI, for AHF and CHF, Angina pectoris attack, Thrombosis
of the central vein of the retina, Combined therapy of hypertensive crisis, Paroxysmal
nocturnal dyspnea, Myocardial infarction and edema of lungs (a special medicinal form
of nitroglycerine for IV injections is used).

43b. Pharmacological characteristic and use of nitroglycerin.

Pharmacological properties:
-is taken sublingually;
-is well absorbed from the oral cavity;
-is metabolized in erythrocytes and in the liver; starts to act 15-30 seconds after
administration and develops peak 3-5min

Mechanism of action
Nitrate (NO2) is transformed into nitrous oxide (= NO, endogenous endothelial-derived
relaxation factor, EDRF).
It binds to SH-groups(thiol) of nitrate receptors.

That results in activation of guanylate cyclase and leads to an increase in the cGMP content
in cells and a decrease in the Ca++ entry.
Such processes lead to the dephosphorylation of the myosin light chain and relaxation
ofvascular smooth muscles

-it causes dilation of venous vessels, decrease peripheral vascular resistance, thus,
decreasing afterload of myocardium.
As a result of this there is a decreasing in the demand of oxygen, dilation of coronary
vessels,redistribution in their blood flow results in increase oxygen supply, inhibition of
impulses from vasomotor center

Uses: angina pectoris attack; thrombosis of the ventral vein of the retina; paroxysmal
nocturnal dyspnea; MI, edema of lungs; hypertensive crisis

Side Effect
Headache (as a result of the dilation of blood vessels in brain tunics and increasing of
intracranial pressure; may be diminished by the applying of Validolum or non-narcotic
analgesics)
Hypotension, postural hypotension, collapse (may be treated by Mesatonum)
Reflex tachycardia
Pain in eyes, an increase in intraocular pressure (as a result of dilation of ocular blood
vessels)
Flushing of the skin

Contraindications: Hypersensitivity Hypotension Myocardial infarction accompanied by

hypotension Hypertrophic obstructive cardiomyopathy Aortic and mitral stenosis Cardiac
tamponade Constrictive pericarditis An increase in intracranial pressure (trauma of the brain,
hemorrhagical insult) Glaucoma

44b. Peculiarities of beta-blockers and Ca-channel blockers as antianginal medications, its

side effects.
Beta blockers
The beta-adrenergic blockers decrease the oxygen demands of the myocardium at rest as
well as at exertion by blocking beta 1 receptors, resulting in decreased heart rate,
contractility, cardiac output, and blood pressure. As such, they can reduce both the
frequency and severity of angina attacks.
beta-Blockers can be used to increase exercise duration and tolerance in patients with
effort-induced angina.
[Note: The exception to this rule is vasospastic angina, in which B-blockers are ineffective and may actually worsen
symptoms.]

B-Blockers reduce the risk of death and MI in patients who have had a prior MI and also
improve patients with heart failure with reduced ejection fraction.
cardioselective beta-blockers, such as metoprolol and atenolol, are preferred for antianginal
therapy at low doses.
CONTRAINDICATIONS:- B-Blockers should be avoided in patients with severe bradycardia; Nonselective B-blockers should
be avoided in patients with asthma. [Note: It is important not to discontinue B-blocker therapy abruptly. The dose should
be gradually tapered off over 2 to 3 weeks to avoid rebound angina, MI, and hypertension.

Side effects:

Bradycardia, hypotension, AV block, heart failure, of peripheral blood circulation, a spasm of

bronchi, gastric ulcer, hypoglycemia (when insulin is coadministered), weakness, drowsiness.

β-Adrenoblocker:

Classification:

1. Non-selective - Propranolol , Oxprenolol & 2.Selective - Metoprolol , Talinolol , Atenolol

Calcium channel blockers
The calcium channel blockers protect the tissue by inhibiting the entrance of calcium into
cardiac and smooth muscle cells of the coronary and systemic arterial beds. All calcium
channel blockers are, therefore, arteriolar vasodilators that cause a decrease in smooth
muscle tone and vascular resistance. These agents primarily affect the resistance of
peripheral and coronary arteriolar smooth muscle.
Calcium channel blockers reduce myocardial oxygen consumption by decreasing vascular
resistance, thereby decreasing afterload. Their efficacy in vasospastic angina is due to
relaxation of the coronary arteries.
All calcium channel blockers lower blood pressure
Side effects:- may cause AV block, heart failure, reflexive tachycardia, hypotension,
peripheral edema.

Calcium channel blockers:(extra)

block calcium channels of L-type and cause an antianginal, anti-antihypertensive action.

Classification:

1. Phenylalkylamines - Verapamil

2. Dihydropyridines - Nifedipine , Amlodipine

3. Benzodiazepines – Diltiazem

A. Dihydropyridine calcium channel blockers

Amlodipine an oral dihydropyridine, functions mainly as an arteriolar vasodilator. The vasodilatory effect of amlodipine is
useful in the treatment of variant angina caused by spontaneous coronary spasm. Nifedipine it is usually administered as
an extended-release oral formulation.
[Note: Short-acting dihydropyridines should be avoided in CAD because of evidence of increased mortality after an MI
and an increase in acuteMI in hypertensive patients.]

B. Nondihydropyridine calcium channel blockers

Verapamil slows atrioventricular (AV) conduction directly and decreases heart rate, contractility, blood pressure, and
oxygen demand. it is a weaker vasodilator. Verapamil is contraindicated in patients with preexisting depressed cardiac
function or AV conduction abnormalities.
Diltiazem also slows AV conduction, decreases the rate of firing of the sinus node pacemaker, and is also a coronary artery
vasodilator. Diltiazem can relieve coronary artery spasm and is particularly useful in patients with variant angina.
Nondihydropyridine calcium channel blockers can worsen
heart failure due to their negative inotropic effect, and their use should
be avoided in this population.

45b. Main principles of treatment of acute myocardial infarction.

Myocardial infarction: is the formation of the area of necrosis in the myocardium due to
local ischemia resulting from the obstruction of blood vessel, most commonly by thrombus
or embolus. Myocardial infarction may be complicated by acute heart failure and
cardiogenic shock.
Principles of treatment of myocardial infarction:
For analgesia: narcotic analgesics, nitrous oxide

For a decrease in ischemia: organic nitrates (nitroglycerine), β-adrenoblockers

For a decrease in arrhythmia: anti-arrhythmics (lidocaine, amiodarone, polarizing solution),
β-adrenoblockers
For the inhibition of blood coagulation: anticoagulants (heparin)
For the lysis of thrombus: thrombolytics: (streptokinase, alteplase)
For a decrease in acute heart failure: inotropic drugs (dobutamine), vasodilators.
46b. Classification of antiarrhythmic drugs (Vaughan-William’s classification). Pharmacological
characteristics and use of class 1A drugs (quinidine, procainamide).

Classification:

- Class I drugs (membrane stabilizers): exert their effect by the inhibition of Na+
channels which decreases the rate of rise of phase-o depolarization & slows
conduction velocity.

- subclass IA blocks Na+ channels which are in the open state; e.g. Quinidine –
Procainamide – Disopyramide

- subclass IB – both in activated and inactivated states; e.g., Lidocaine – Phenytoin –

Mexiletine

- subclass IC includes the most potent agents with a more significant action on open
channels. E.g. Propafenone – Flecainide – Ethacyzin

- Class II drugs increase the refractory period of the AV node. E.g., Propranolol –
Metoprolol

- class III block K+ channels resulting in the prolongation of repolarization (Phase 1&3).
e.g. Amiodarone – Dronedarone – Bretylium – Sotalol

- Class IV (affect av node) blocks Ca++ slow inward movements during Phase 2, thus
increasing the duration of the refractory period. E.g., Verapamil – Diltiazem

- Class V. Agents of other or unknown mechanisms: Adenosine

Cardiac glycosides – Digitoxin – Digoxin

Potassium preparations – Pananginum.

Magnesium preparations – Rythmocor – Magnesium orotate,

Quinidine:

is taken orally, has the duration of action of 6-8 hrs; inhibits excitability, automaticity, and
conductivity in the atria, AV node, bundle of His and Purkinje fibers, inhibits ectopic
arrhythmias, ventricular arrhythmias caused by increased normal automaticity, prevents
re-entry arrhythmias,

decreases the contractility of the myocardium, has M-cholinoblocking properties and can
induce tachycardia in normal individuals;

use: in the treatment of atrial, AV junctional, and ventricular arrhythmias, is applied to

maintain the sinus rhythm after the direct current cardioversion; may cause the
deformation of the QRS complex, some kinds of ventricular tachyarrhythmia, heart block,
asystole

Procainamide:

is administered orally, IM, IV, has a half-life of 2-3 hrs, is acetylated in the liver to N-acetyl
procainamide which has properties of class III drug; is not toxic, does not inhibit contractility;
side-effects, such as AV block, reversible lupus erythematosus-like syndrome, nausea,
vomiting, seizures, asystole, and the induction of ventricular arrhythmias (in overdose).

Use: in the treatment of atrial fibrillation in the setting of Wolff-Parkinson-White (WPW)

syndrome, and in the treatment of a wide complex of hemodynamically stable tachycardias.
While procainamide and quinidine may be used in the conversion of atrial fibrillation to the
normal sinus rhythm, they should only be used together with an AV node blocking agent

47b. Pharmacological characteristic and use of Lidocaine (Xycaine), Ethmosine,

Propranolol and Verapamil as antiarrhythmic drugs.
Xycaine(Lidocaine)1b class (Na channel blocker): Also, lidocaine and mexiletine shorten
phase 3 repolarization and decrease the duration of the action potential. administered IV, IM.
It is a drug of choice in case of heavy ventricular arrhythmias (extrasystoles, paroxysmal
tachycardia, fibrillation) of different origin, includingacute myocardial infarction (0,2 % sol. i. v.
very slowly).

 Uses: It is drug of choice in emergency treatment of cardiac arrhythmias

Alternate is amiodarone for use in ventricular fibrillation or pulseless ventricular

tachycardia (VT),.

Side effects – vertigo, seizures, suppression of respiration, nausea, vomiting, hypotension,

bradycardia.

Ethmosin(Ethcyzin)1c class (Na-channel blocker) : oral administration with long action. It

increase duration of atria and AV node, slow the rate of increase in AP in the atrial and
ventricular fibers of purkinje, suppress SA conduction.

 Used for the prophylaxis and treatment of serious and life-threatening ventricular
arrhythmias, supraventricular extrasystole, paroxysm of fibrillation,

Propranolol 2 class (beta blocker): prevent the action of catecholamines on the myocardium,
diminish Phase 4 depolarization. As a result, they prolong the refractory period and decrease
conductivity. They act by slowing conduction through the AV node. They depress automaticity, thus
β-adrenoblockers decrease the heart rate and contractility.
 Use: Tachyarrhythmia caused by increased sympathetic activity Atrial flutter and fibrillation
AV nodal re-entrant tachycardia.
 Side-effect: AV block Bradycardia Worsening in CHF.

Anaprilin 2 class (beta blocker): sinus tachycardia (for thyrotoxicosis), supraventricular

extrasystole, paroxysmal tachycardia, including acute myocardial infarction

Verapamil 4 class is a calcium channel blocker from the first generation; is administered
orally and IV; is well absorbed in the GI tract; develops a peak concentration in 1-2 hrs; has
a half-life of 3-6 hrs; undergoes first-pass biotransformation in the liver; is excreted with
urine; has astrong action on heart rate, as well as vasodilation;

 Used: for the treatment of tachyarrhythmia (paroxysmal tachycardia, extrasystolia,

scintillating arrhythmia), angina pectoris, hypertension, for the termination of
arrhythmia paroxysm;
  may cause AV block, heart failure, an increase in digitalis toxicity when it is given
together with digitalis preparations.

48b. Pharmacology of Amiodarone: mechanism of action, use, side effects.

Amiodarone is an anti-arrhythmic drug of third class(potassium channel blocker). The action
is increase the duration of action potential.

It is a benzofuran derivative; is administered orally or IV; binds to plasma proteins; is

metabolized in liver and excreted with bile; blocks Na, Ca and K; increases the duration of
AP;has antiarrhythmic action; produces systemic and coronary vasodilation resulting in
antianginal action;

Mechanism of action: preferentially, blocks inactivated Na+ channel, partially inhibits

myocardial Ca+ channels, non-competitively blocks beta – adrenergic receptors, alters
thyroid function(due to its structural similarity to thyroxine).also has alpha blocker activity.
Its dominant effect is prolongation of action potential duration and refractory period by
blocking potassium channels (without altering resting membrane potential, instead they
prolong effective refractory period).
Slow down conduction and ectopic automaticity.
IV injection causes myocardial depression and hypotension.

Uses: treatment of ventricular and supraventricular arrhythmias, ventricular fibrillation,

angina pectoris, MI and for prevention of sudden coronary death; may cause pulmonary
fibrosis, bradycardia, AV block, phototoxixity, blurred vision, hyperthyroisism,
hypothyroidism, ataxia, tremor, anorexia, nausea, vomiting .

Side effects: fall in BP, bradycardia, photosensitization, sun burn, malaise, fatigue,increased AST
or ALT levels.

49b. Anti-coughing and expectoration drugs, pharmacodynamics, mechanism of action,

use.
ANTI-COUGH or Antitussives –
Two types central action and peripheral action.

1. Central action-
(i) Opioids: Codeine phosphate suppress tussive center, ethyl morphine hydrochloride,
dextromethorphan.
(ii) Non-opioids: Glaucine hydrochloride(glauvent) inhibits medulla center of cough and treats
diseases of lungs and bronchi accompanied by dry cough, oxeladin citrate (tussuprex),
butamirate citrate (sinecod).

2. Peripheral action- Prenoxdiazin hydrochloride (libexin) has broncholytic and local

anesthetic effect and is used for dry cough, glibexin.
Falimint has antitussive and antimicrobial effects.
Expectorants:
1. secrete-motor drugs (stimulate expectoration) –
a) drugs of reflex action – drugs of medicinal plants, sodium benzoate, bronchium elixir,
mucaltin.

b) drugs of resorbtive and local action – bromide sodium and potassium, ammonium
chloride, sodium hydrocarbonate, ether oils.

Benzonatate
suppresses the cough reflex through peripheral action. It anesthetizes the stretch receptors
located in the respiratory passages, lungs, and pleura.
Side-effects: include dizziness, numbness of the tongue, mouth, and throat. These localized
side effects may be particularly problematic if the capsules are broken or chewed and the
medication comes in direct
contact with the oral mucosa.

2. bronchosecretolytic drug(mucolytics) –
a) proteolytic enzymes – trysin, chymotrypsin, chymosin, deoxyribonuclease.
MOA-It activates hydrolytic enzymes, increase the release of lysosomes from Clarck's cells.

b) mucolytics – acetylcysteine, carbocysteine.

MOA-the drug stimulates serous cells of the bronhial mucous membrane, regulates the ratio
between serous and mucous components in sputum.

c) drugs which increase surfactant production (bromhexine, ambroxol)or preparation

ofsurfactant(alveofakt, ekzosurf).
MOA-It stimulates production of surfactant in the lungs and activates the transport function
of ciliated cells.

Pharmacodynamics:
-expectorant action;
-mucolytic action

Uses: pneumonia, bronchial asthma, bronchoectasis, respiratory distress-syndrome in

newbon, acute and chronic diseases of airways accompanied by the formation of dense
sputum and non-productive cough

50b. Bronchodilators, mechanism of action, use, side effects.

Classification :
1. Beta-2 Adrenomimetics – Salbutamol, Terbutaline, Bambuterol, Salmeterol

MOA – relax airway smooth muscles and inhibit the release of substances from mast
cells which cause bronchoconstriction.

Uses – asthma attacks, mild intermitted asthma.

Side effects – nervousness, shaking, headache, throat dryness, nausea, cough, change
 in taste.

2. Methylxanthines (phosphodiesterase inhibitors) – Theophylline,

Aminophylline,Choline
MOA – they block the adenosine receptor. They inhibiting PDE(Phosphodiesterase) resulting
in anincrease of cAMP concentration and decrease calcium content inside the cells.

Use – Bronchial asthma, spasm of bronchi of different origin, chronic obstructive bronchi,
status asthmaticus, emphysema of lungs, nocturnal apnea, apnea of new born, lungs
hypertension.
Side effects – restlessness, insomnia, tremor, seizures, tachycardia, arrythmia, hypotension,
atony of gut, allergic reaction

Anticholinergics - Ipratopium bromide, Tiotrotium bromide.

MOA – they increase the cGMP concentration, decrease calcium concentration leads to
smooth muscles relaxation.
Uses – wheezing, shortness of breath, coughing, chest tightness, COPD, chronic bronchitis,
emphysema.
Side effects – dry mouth, cough, nausea, dizziness, sedation, acute angle closure glaucoma,
tachycardia.

51b. Mechanism of action and use of emetic and anti-emetic

drugs.EMETIC DRUGS: are medications provoking vomiting.
They are divided into:

 Drugs of central action –- Apomorphine hydrochloride

 Drugs of the peripheral action: plant drugs of Thermopsis, Ipecacuanha, sulfates of zinc and
copper.

Apo-morphine hydrochloride acting on the chemoreceptors of the trigger zone (CTZ)

connecting to the emetic center.
1) Apomorphine is a dopaminergic preparation.
2)It causes stimulation of CTZ and provokes vomiting;
3)used in acute poisonings
4) cause the rupture of stomach wall and esophagus,
5)an increase in BP;
6) contraindicated in poisonings with acids and alkalis, ulcer of the stomach, acute
abdomen, severe hypertension, pregnancy.
Drugs of the peripheral action
1. plant drugs of Thermopsis, Ipecacuanna, sulfates of zinc and copper.
2. administered orally,

3. irritate sensitive nerve endings in the stomach and cause vomiting reflexly. Now these
preparations are used rarely.

ANTI-EMETIC DRUGS: these are the drugs that are used to stop vomiting.
1) cholinergic antagonists - Scopolamine

 is M-cholinoblocker
 inhibits activity of 8th pair of cranial nerves and decrease motion sickness.
 Drug should be taken 30 min before the start of travel and repeated every 4 to 6 hrs.
 If it is applied transdermally can provide effective protection for up to 3 days.
2) H1 antihistamines - promethazine, diphenhydramine .

 They block H1 histamine receptors , cholinergic receptors and adrenergic and

serotonin receptors.
 Used as antiemetic to prevent kinetosis, cytotoxic drug-induced, or postoperative
vomiting, emesis due to radiation sickness.
3) Neuroleptics : Phenothiazines (e.g., Chlorpromazine)

 may suppress nausea and vomit that follow the surgery or are due to opioid
analgesics, gastrointestinal irritation, uremia, an elevated intracranial pressure.
4) D2 dopamine receptor antagonist : Domperidone

 is peripherally selective dopamine D2 receptor antagonist.

 Used in nausea, vomiting, increase the transit of food through the stomach by
increasing gastrointestinal peristalsis; promote lactation by release of prolactin.
 It can be used to relieve gastrointestinal symptoms in Parkinson's disease because it
blocks peripheral D2 receptor, but doesn't cross Blood Brain Barrier in normal doses.
5) Serotonin-antagonists: Ondansetron (or Zofran)

 used to prevent nausea and vomiting caused by cancer chemotherapy, radiation

therapy, or surgery.
 used in gastroenteritis and treatment of morning sickness and hyperemesis
gravidarum of pregnancy
 52b. Mechanism of action of H2-histamine blockers, M1-cholinoblockers, blockers of H+ -
K+ATP, cholinergic and adhesive drugs, its use for treatment of peptic ulcer.
-H2-histamine receptors blockers: (Famotidine, Ranitidine)

They inhibit the secretion of hydrochloric acid in the stomach by competing, inhibition of
the histamine interaction with H2- histamine receptors of stomach cells. Is used in case of
peptic ulcer; hyper acidic gastritis
M1-cholinoblockers(Pirenzepine, Atropine):
they block M1-ChR of the gastric mucous membrane selectively and it leads to the inhibition
of the hydrochloric acid and pepsinogen secretion by the gastric glands. Is used to treat
peptic ulcer; hyperacidic gastritis
Blockers of H/K-ATPase pump(Omeprazole)
they inhibit the activity of the pump, thus stopping the hydrogen ions secretion by oxyntic
cells of the stomach and is accompanied by the inhibition of the hydrochloric acid
formation. Is used to treat peptic ulcer; hyperacidic gastritis
Adhesive drugs(Maalox)
form a film from colloid that protects the sensitive nervous endings of the gastric mucous
membrane from the action of irritants and the hydrochloric acid. Is used to treat gastritis,
hyper-acidic gastritis; ulcer(peptic, duodenal)

53b. Antacids: mechanism of action, use, side effects.

These are basic substances which neutralize gastric acid and raise pH of gastric contents.
They contain H+-binding groups, such as carbonate ion(CO32-), bicarbonate (HCO3- )or
hydroxide (OH-.)
There are systemic and non-systemic antacids.
Systemic: sodium bicarbonate and citrate

Non-systemic: magnesium hydroxide, aluminium hydroxide.

SYSTEMIC ANTACIDS

 Sodium bicarbonate It is water soluble, acts instantaneously, but the duration of

action is short. It is a potent neutralizer (1 g → 12 mEq HCl), pH may rise above 7.

Mechanism of action- binds to hydrogen to form carbonic acid which

Further dissociate to carbon dioxide and water
Use of sod. bicarbonate is restricted to casual treatment of heartburn. It provides
quick symptomatic relief. Other uses are to alkalinize urine and to treat acidosis.

side effects
(a) Absorbed systemically: large doses will induce alkalosis.
 (b) Produces CO2 in stomach → distention, discomfort, belching, risk of ulcer
perforation.
(c) Acid rebound occurs, but is usually short lasting.
(d) Increases Na+ load: may worsen edema and CHF.

 Sodium citrate has poperties similar to sod. bicarbonate; 1 g neutralizes 10 mEq HCl;
Uses- used in metabolic acidosis, in gout to make urine less acidic and different
kidney problems.

NON-SYSTEMIC ANATACIDS
These are insoluble and poorly absorbed basic compounds ,they react in stomach to form
the corresponding chloride salt. The chloride salt again reacts with the intestinal
bicarbonate so that HCO3 is not spared for absorption—no acid-base disturbance occurs.

 Mag. Hydroxide: its has low concentration of OH¯ions and thus low alkalinity. It
reacts with HCl promptly and is an efficient antacid (1 g → 30 mEq HCl).Rebound
acidity is mild and brief.

Mechanism of action -it reacts with HCL to form magnesium chloride (MgCL2) and
water . Uses- used as a laxative to relive constipation, indigestion, heart burn and air
stomach
Side effects – excessive thirst, nausea, stomach cramps and vomiting .

 Aluminium hydroxide gel is a weak and slowly reacting antacid. ( 1–2.5 mEq/g. ) The
Al3+ ions relax smooth muscle. So, it delays gastric emptying.
Uses- used in combination with magnesium hydroxide for to relive heart burn, acid
indigestion and upset stomach, hyperphosphatemia and phosphate stones.
Side effects - Alum. hydrox. frequently, causes constipation due to its smooth
musclerelaxant and mucosal astringent action. Alum. hydrox. binds phosphate in
the intestine and prevents its absorption so hypophosphatemia occurs on regular
use.This may also cause osteomalacia .
Other antacids include Magnesium trisilicate, Calcium carbonate.
54b. Principles of combinative treatment of peptic ulcers.
Peptic ulcer disease takes two very different ways, depending on the predominant location
of the gastritis in the stomach.
Some individuals produce excessive quantities of acid (hypersecretion of acid), and this leads to the development of
duodenal ulcer. This type of response occurs when gastritis is localized in the pyloric region.

PRINCIPLES
- Eradication of H. pylori through the use of antibiotics
- Reduction of acid secretion (Reducing the acidity in the stomach lumen promotes
healing, and it also increases the effectiveness of the antibiotics)
- Protection of gastric mucosa
- Replacement therapy in the condition of acid hyposecretion.
- Pentagastrin and diluted HCL can be used for hyposecretion.

Combination drug therapy regimens pylori infection include:

(i) A proton pump inhibitor (PPI) + clarithromycin + amoxicillin or metronidazole.

(ii) A proton pump inhibitor plus a bismuth compound plus metronidazole plus tetracycline.

De-nol + amoxicillin
De-nol + Metronidazole
Omeprazole + Amoxicillin + clarithromycin
De-nol + Clarithromicin + Metronidazole
De-nol + Pantoprazol + Amoxicillin, Clarithromycin

De-Nol stimulates gastric and duodenal alkaline secretion through prostaglandin dependent
mechanism.
De-nol is a preparation containing bismuith preparation against peptic ulcer with citrate
coating. bismuith preparation help in treating infection of traveller diarohea which led to
peptic ulcer progressively.

Amoxicillin is in the class of beta-lactam antimicrobials(semisynthetic). Beta-lactams act by

binding to penicillin-binding proteins that inhibit a process called transpeptidation (cross-
linking process in cell wall synthesis), leading to activation of autolytic enzymes in the
bacterial cell wall.
Clarithromycin, a semisynthetic macrolide antibiotic derived from erythromycin, inhibits
bacterial protein synthesis by binding to the bacterial 50S ribosomal subunit. Binding
inhibits peptidyl transferase activity and interferes with amino acid translocation during the
translation and protein assembly process.
Metronidazole diffuses into the organism, inhibits protein synthesis by interacting with DNA
and causing a loss of helical DNA structure and strand breakage. Therefore, it causes cell
death in susceptible organisms
55b. Classification of cholagogue agents, mechanism of action, use.
A cholagogue is a medicinal agent which promotes the discharge of bile from the system,
purging it downward.

Classification

1. Drugs which stimulate bile production (choleretics, cholesecretics)

(i) Drugs which increase secretion of bile and stimulate production of bile acids (real
choleretics)

(a) drugs which contain bile acids (alcohol used in constipation and dyspepsia,
cholenzyme used in gastritis, achillia, enterocolitis)

(b) synthetic drugs (nicodine, oxafenamide)

(c) drugs of plant origin (common immortelle, stigma of corn, pepper mint, tansy, dog-
rose).

(ii) Drugs which increase secretion of bile primarily due to water component
(hydrocholeretics: mineral waters, valerian drugs).

2. Drugs which stimulate bile flux (cholekinetics).

(i) drugs which cause increasing of gall-bladder tone and decreasing of bile ducts tone
(cholekinetics: magnesium sulfate, sorbit, barberries).
(ii) drugs which cause relaxation of bile ducts tone (cholespasmolytics: M-cholinoblockers
atropine, euphyllin, nitroglycerine).

A bile acid used for the treatment of primary biliary cirrhosis (PBC), dissolution of
radiolucent gallstones in patients with a functioning gallbladder, and treatment of
hepatobiliary disorders associated with cystic fibrosis in pediatric patients.

56b. Drugs for treatment of acute and chronic pancreatitis, their pharmacodynamics,
mechanism of action.
Drugs used in acute pancreatitis
-directly inhibitors of proteolysis and fibrinolysis - (Aprotinin and contrykal).

-Aminocaproic acid has mixed mechanism of action, inhibits proteolytic enzymes, exerts
anti allergic and anti toxic action.

Drugs used during chronic pancreatitis – Pancreatin, Mezym forte, Festal:

these drugs should be used with Combined preparations containing protease, amylase,and
lipase are suitable in this case. They are suitable for enzyme replacement therapy.

Pharmacodynamics:
-antifibrinolytic action; Aprotinin intravenously
-antiproteolytic action– Pancreatin oral administration
 Mechanism of action

Inhibitors of pancreatic enzymes are most essential in the treatment of acute pancreatitis.
Aprotinin and contrykal are directly acting inhibitors of proteolysis and fibrinolisis.
Aminocaproic acid has a mixed mechanism of action, inhibits proteolytic enzymes, excerts
anti-allergy and anti-toxic actions.
Enzyme replacement therapy is used in chronic pancreatitis.
Combined preparations containing protease, amylase, and lipase are suitable in this case.

57b. Laxative drugs, mechanism of action, use.

Laxatives- stimulate afferent nerves to initiate a reflex increase in gut motility
Laxatives are classified according the site of action, as well as by the origin.
 Plant cathartics are divided into oils (Castor oil) and the drugs consisting of
anthraguinone derivatives.
• Castor oil (Oleum Ricini) is bean oil which is hydrolyzed in the gut to the
ricinoleic acid and glycerol. The ricinoleic acid acts on the ileum and colon to
induce an increased fluid secretion and colonic contraction It is used in acute
constipation
• Anthraguinone derivatives (drugs of Senna, Rheum, Aloe, etc). They are
transformed to anthranol which irritates receptors of colon and produces
evacuation in 8-10 hrs. The main drugs are senadexin, senade, cafiol etc.

 Synthetic drugs – isaphenin, bisacodyl, sodium picosulfate (guttalax) also

irritate colon receptors and are used as anthraguinone derivatives in
chronicconstipation.

 Osmotic purgatives (magnesium sulfate, sodium sulfate) increase lumen

osmolarity, drive additional fluid into the GI tract, and irritate intestine
receptors. They are used in intoxication, acute constipation, before some
diagnostic procedures, or in treatment with some anthelminthics
‘Kpharma’

THIRD EXAM QUESTION

1c. Diuretics, mechanism of action, use.

Ans:- Diuretics are drugs which cause a net loss of Na+ and water in urine. They increase
production of urine. These drugs have a direct renal action. Their predominant action is
urine excretion by inhibiting reabsorption of NaCl and water.
Classification:
1. Thiazides : Hydrochlorothiazide (Dichlothiazide) , Indapamide
2. Loop diuretics: Furosemide (Lasix), Ethacrynic acid, Torsemide
 3. Carbonic anhydrase inhibitors: Acetazolamide (Diacarbum)
4.Potassium-sparing diuretics: Spironolactone, Triamterene
5.Osmotic diuretics: Mannitol, Urea

Mechanism of action:

1) Thiazides (hydrochlorothiazide) is secreted into the tubular fluid by proximal

tubule cells. {most commonly prescribed diuretics.}

 It decreases Nacl reabsorption by inhibiting, Na+ /Cl- cotransport system in the

D.C.T & also causes vasodilation (by reducing peripheral vascular resistance.)

 In the distal convoluted tubule, it blocks K+/Na+-ATP-ase and succinate

dehydrohynase and inhibits energetic metabolism.
 Inhibition of energy production blocks Na+, a Cl- symporter that isassociated
with the luminal (basal) membrane.
 A decrease in an active transport of Na+ to the blood leads to the elevation of
Na+ concentration in the cell and inhibition of a passivetransport of Na+ and
Cl- through the apical membrane.
 Na+, CL-, K+, and water stay in primary urine and are excreted. Theresult is a
diuretic action.

Use: Hypertension, Edema caused by CHF or hepatic cirrhosis , Glaucoma.

Treatment with corticosteroids and estrogens, Diabetes insipidus
Renal disturbances (nephrotic syndrome, acute glomerulonephritis, chronic renal
failure)

Side effect- Hypokalemia, Hyperuricemia, Hypotension, Hyponatremia,

Hypercalcemia.

2) Furosemide (Lasix):
they act by inhibiting the Na+ - K+ - 2Cl- cotransport system in the thick ascending limb of
loop of Henle (TAL). Increase elimination of NaCl ion.
Uses – acute pulmonary edema, hypertension, refractory edema, acuterenal hypovolemic
failure, hypercalcemic states.
Side-effect- Ototoxicity, hyperuricemia, Hypotension, Hypomagnesemia,
hypokalemia.

3) Acetazolamide (Diacarbum) act in PCT.

It reduces reabsorption of bicarbonate in the P.C.T

catalyzes CO2 hydration or dehydration reaction to generate H+ which is secreted into

tubular fluid in exchange for a Na+. When this enzyme is inhibited, these reactions are
slowed down so that less Na+ , HCO3 and water are reabsorbed from the fast flowing
tubular fluid.
Uses – acute glaucoma, acute mountain sickness, epilepsy, metabolicalkalosis.
4) Spironolactone {2 group} (Potassium sparing diuretics)
act by regulate Na reabsorption and K secretion in DCT and collecting duct. They are
structurally similar to aldosterone and binds to mineralocorticoid receptor and decrease
action of aldosterone.
spironolactone block androgen receptors and hence inhibit steriod synthesis at high
doses which may be the cause of gynecomastia in man,but this character made it useful
as a off label PCOS treatment.

Uses – congestive heart failure, hyperaldosteronic state, femalehirustism,.

Side effect -hypokalemia, gynacomastia.

5) Triamterene {1 group} closes Na+ pores in the apical membrane of cells in collecting
tubules increases Na and water excretion and reduces the loss of K. Uses:
hypotension

6) Mannitol , Urea ( Osmotic diuretic)

It inhibit water reabsorption in PCT and LOOP OF HENLE.
Increase water elimination more than sodium.
Can’t used for hypertension and congestive heart failure because it increases
peripheral resistance and hencemay lead to hypertensive crisis.
Uses – glaucoma, in oliguric states, prophylaxis of renal hypovolemicfailure.

2c. Highly effective diuretics: pharmacodynamics, mechanism of action, use,side effects.

Ans:- Highly effective diuretics are
1. Loop diuretics : FUROSEMIDE , Bumetanide, Torasemide.
2. potassium sparing diuretics: SPIRONOLACTONE

FUROSEMIDE

Pharmacodynamics – they are absorbed orally over 2-3 hours. Lipid solubility is low, and
it is highly bound to plasma proteins. It Is mainly excreted unchanged by glomerular
filtration as well as tubular secretion.
Show synergism with ethacrynic acid (loop diuretic) and that’s why
simultaneous use of them is contraindicated.

Drug interaction with acebutalol (beta 1blocker). acebutolol increase serum potassium
levels while furosemide decreases serum potassium levels
Mechanism of action - they act by inhibiting absorption in the Na+ - K+ - 2Cl- cotransporter in
the thick ascending limb of loop of Henle (TAL). Increase elimination of NaCl ion. They also
inhibit magnesium and calcium reabsorption in the thick ascending limb. They also stimulate
release of renin, which through Renin-angiotensin system, increase fluid retention. Thus
increase GFR.
Uses – acute pulmonary edema- I.V. administration of furosemide., cerebral edema,
hypertension, hypercalcaemia of malignancy, congestive heart failure,chronic kidney
disease.
Side effect – Sulfonamide hypersensitivity, hypokalemia and alkalosis,
hypocalcemia, hypomagnesemia, hyperuricemia, ototoxicity.
Contraindications: acute glomerulonephritis, acute renal failure, anuria, obturation of
urinary pathways, hepatic coma, pancreatitis, disturbances in electrolyte balance, gout,
diabetes mellitus, hypotension, lupus erythematosus, first half of pregnancy, lactation.

SPIRONOLACTONE

Pharmacodynamics -is a competitive antagonist of aldosterone

Mechanism of action - inhibits synthesis of permeases that results in the inhibition of a

passive transport of Na+ through the apical membrane in collecting tubules; does not act
on the excretion of K+; the diuretic and natriuretic effects of spironolactone are modest is
used as an adjunct to otherdiuretics to reduce a loss of K.

When given with K supplements, can cause dangerous hyperkalemia

ASPIRIN blocks its action by inhibiting tubular secretion of its active metabolite (canrenone)

Spironolactone increases plasma DIGOXIN concentration.

Uses - used to treat heart failure, high blood pressure (hypertension), or hypokalemia
(low potassium levels in the blood).

Side effects :- Allergic Reactions , Severe Skin Reactions

3c. Thiazide diuretics: pharmacodynamics, mechanism of action, use, side effects.

is secreted into the tubular fluid by proximal tubule cells. {most commonly
prescribed diuretics.}

Mechanism of action:

 It decreases Nacl reabsorption by inhibiting, Na+ /Cl- cotransport system in the

D.C.T & also causes vasodilation (by reducing peripheral vascular resistance.)

 In the distal convoluted tubule, it blocks K+/Na+-ATP-ase and succinate

dehydrohynase and inhibits energetic metabolism.
 Inhibition of energy production blocks Na+, a Cl- symporter that isassociated
with the luminal (basal) membrane.
 A decrease in an active transport of Na+ to the blood leads to the elevation of
Na+ concentration in the cell and inhibition of a passivetransport of Na+ and
Cl- through the apical membrane.
 Na+, CL-, K+, and water stay in primary urine and are excreted. The result is a
diuretic action.
Pharmacodynamics:

- enhance in Na+, Cl- excretion (the effect on Na+ is small because most of
the Na+ has already been absorbed prior to reaching the distal tubule)

- an enhance in K+ excretion,
- a reduce in uric acid excretion
- a decrease in Ca++ excretion, enhance in the excretion of Mg++
- an increase of diuresis and a decrease in volume of blood
- the reduction of peripheral vascular resistance and lowering of BP
- a decrease in diuresis in patients with diabetes insipidus
- a decrease in intraocular pressure
Use: Hypertension, Edema caused by CHF or hepatic cirrhosis, Glaucoma.
Treatment with corticosteroids and estrogens, Diabetes insipidus
Renal disturbances (nephrotic syndrome, acute glomerulonephritis, chronic renal
failure)

Side effect- Hypokalemia, Hyperuricemia, Hypotension, Hyponatremia,

Hypercalcemia.

4c. Treatment of acute and chronic gout.

Ans :- Acute Gout treatment

1. NSAIDs such as indomethacin which block cyclooxygenase1 and thereby reduce
generation of prostaglandin. It relieve gout pain.
(Side effect:- ringing in the ears, irritation of rectum)

2. Colchicine (dose- 0.5mg/day) and – Mechanism of action: binds to tubulin →↓

microtubular polymerization, ↓ LTB4, and ↓ leukocyte and granulocyte migration intra
articular steroids are alternatives. Colchicine binds to tubulin decrease leukocyte and
granulocyte migration into the inflamed joint.
Chronic administration may lead to myopathy, neutropenia, aplastic anemia, and alopecia
3. Corticosteroids- injection of triamcinolone acetonide given in finger toe joint. Urate
lowering therapy may be used prophylactically if the person has chronic kidney disease
or 2 attacks of acute gout every year.

Chronic Gout treatment

1. Uricosuric drugs – such as probenecid {SALICYLATES blocks its uricosuric action}

 (inhibits PENICILLIN, by prolonging its duration of action) and sulfinpyrazone. they
inhibit renal tubular transporter there by facilitating the excretion of uric acid by
blocking reuptake of urate.
2. Uric acid synthesis inhibitor – such as allopurinol, pegloticase and
febuxostat. Allopurinol (100 mg OD)and febuxostat inhibit xanthine
oxidase thereby decrease purine metabolism and in turn decrease uricacid.
3. Pegloticase (8 mg every 2 day) metabolize uric acid to allantoin ad decrease plasma
uric acid. Pegloticase – Mechanism: recombinant urate-oxidase enzyme for
refractory gout; metabolizes uric acid to allantoin→↓ plasma uric acid

Adverse effects: Allopurinol is well tolerated by most patients.

Hypersensitivity reactions, especially skin rashes, are the mostcommon
adverse reactions.

5c. Pharmacology of drugs affecting myometrium activity.

Ans:- Uterine motility is maintained by autonomic nervous system and hormones.

Stimulation of alpha adrenoreceptors increase uterus contractility and stimulation of beta
adrenoreceptors leads to relaxation of uterus.

Drugs stimulating myometrium ( uterotonics)

1. Stimulants of rhythmic contractions
a) prostaglandins: Dinopros (iv,intravangially)
(PgF2α), Dinoprostone (orally) (PgE2)
b) hormones: Oxytocin, Estrone, Estradiol dipropionate
c) other preparations : Neostigmine , Castor oil , Calcium chloride
2. Stimulants of uterine tone
a) ergot alkaloids : Ergometrine maleate
b) agonists of oxytocin receptors : Carbetocin (Pabal)

 OXYTOCIN ( posterior pituitary hormone)

 (Administration: IM, IV, into the wall of uterus, intranasally)

MOA:

 acts on oxytocin receptors on the cell membranes in the myometrium,causes the

depolarization of membranes and an influx of calcium, increases excitability,
stimulates rhythmic contractions of the myometrium, promotes labor activity;
also stimulates milk production and ejection

uses: stimulation of labor activity, the treatment of postpartum uterine bleeding,

the stimulation of lactation
side effects: nausea, vomiting, heart arrhythmia in the fetus , urine retention ,the elevation
of BP, a tetanic contraction of myometrium , hyperstimulation of labor activity resulting in
the fetus hypoxia , hypoxia of the fetus.
Dinoprost (PgF2α) (administered IV, intravaginally, intra-amnionally)
Moa:
increases the sensitivity to oxytocin, produces the stimulation of rhythmic
contractions of the myometrium in any terms of pregnancy,
relaxes the cervix of the uterus
uses: stimulation of labor and initiation of artificial abortion
side-effects: nausea, vomiting, diarrhea, tachycardia, a spasm of bronchi, an increase in BP
and an elevation of intraocular pressure.
(Contraindication: patients with scars of the uterus, severe diseases of the cardio-
vascular system, liver, and kidney; bronchial asthma, glaucoma).

Ergometrine maleate
Moa:
increases the uterus tone and terminates postpartum bleeding caused by a low tone of the
myometrium; through alfa-1 & Serotonin receptors.
uses: treatment of postpartum bleeding and slow postpartum involution of theuterus.
Side effects: acute and chronic poisoning (ergotisms), trophy disturbances, psychic
disorders.

6c. Pharmacology of drugs that are used for treatment of hypo- and
hyperchromic anemias.
Ans:- Drugs for hypochromic anemia -
- iron preparations- Ferrous lek (iron dextran), Ferrous sulphate,
- cobalt preparations- Coamide
- combined preparations- Ferovenum, Ferroplex, Hemostimulinum
- adjuvant hematinic- Erythropoietin
Erythropoietin stimulates erythroid proliferation and differentiation by interacting
with specific erythropoietin receptors on red cell progenitors. It also induces release of
reticulocytes from the bone marrow,
Recormon
Mechanism of action:
- is used to form hemoglobin in erythrocytes;
- is used to form myoglobin in muscles;
- is used to form enzymes;
- increases the synthesis of erythropoietin, promotes the including of iron into hemoglobin
(Coamide);
- stimulates the synthesis of oxido-reductases needed for normal function of CNS
(Hemostimulinum)
Use: hypochromic anemia of various etiology(anemia from an acute and chronic blood
loss, alimentary iron deficiency, pregnancy, etc.)

Drugs used to treat hyperchromic megaloblastic anemia:

Cyanocobalamin, Folic acid
Mechanism of action: is biotransformed to cobalamine, co-factor of the folic acid reductase,
takes part in the synthesis of purine and pyrimidine, normalizes blood film (the quantity and
quality of erythrocytes, leukocytes and thrombocytes) and take part in the synthesis of
myelin and acetylcholine.
Usings: hyperchromic megaloblastic anemia, hypoplastic anemia, radiation sickness,
neurological diseases, liver diseases, dystrophy in children, glossitis, inpregnancy to prevent
neurological pathology of the fetus and newborn
Deferoxamine- antidote for iron toxicity.

7c. Antiplatelet medications: mechanisms of action and therapeutic use.

Ans:- Anti-platelets are preparations which inhibit platelet aggregation inblood.

 COX-inhibitors : Acetylsalicylic acid (Aspirin)
 Inhibitors of phosphodiesterase : Dipyridamole , Pentoxifylline
 Inhibitors of ADP-mediated aggregation : Ticlopidine (Ticlide),Clopidogrel
 reversibly inhibits COX-1 – other NSAIDs except aspirin

Aspirin: non selective inhibitor of COX1 and COX2

Moa: irreversibly inhibits platelet COX-1which prevents the synthesis of
thromboxane A2 and decreases platelet aggregation
Use: Rheumatism , fever , arthritis, gout, thombophlebitis,
dysmenorrheal Toothache, headache, prevention of colorectal
cancer.

Dipyridamole
Moa: inhibits adenosine desaminase and phosphodiesterase in platelets
increases cAMP concentration in the cells and inhibits thromboxane
A2 synthesis
 that leads to a decrease in platelet aggregation. It also increases
the prostacyclin level.
Uses: angina pectoris attack , thrombosis , atherosclerosis

Ticlopidine
Moa: irreversibly blocks purinergic receptors for ADP in platelet
membranes.
The inhibition of ADP-induced expression of glycoprotein IIb/IIIa receptors
in the platelet membrane decreases platelet aggregation.

Uses: neutropenia and thrombotic thrombocytopenic purpura

Clopidogrel (prodrug)
specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor, which
is important in activation of platelets

common uses of antiplatelets:

The prevention of thrombosis and re-thrombosis
The prophylaxis of MI and insult
The prophylaxis of thrombosis after surgeries
Angioplasties , Thrombophlebitis.
The prevention of thrombosis in patients with prosthetic cardiac valves

8c. Pharmacological characteristics and use of hemostatic.

Ans:- Hemostatic drugs are those which promote hemorrhages stoppage.
Classification -
1. Natural components of blood clotting and drugs which promote their
production -
(i) drugs of local action (thrombin, haemostatic sponge, fibrin film)
(ii) drugs of systemic action (fibrinogen, vitamin К, vikasol, calcium chloride)
2. Antifibrinolytic drugs (fibrinolysis inhibitors) -
(i) of direct action: (contrykal, trasisol, tzalol, gordox)
(ii) of intermediated action: aminocapronic acid, tranexamic acid, amben
(pamba)
3. Drugs which increase blood viscosity - (medical gelatin)
4. Protectors of vessels
(i) synthetic (ethamzilate, Ca dobesilat, androxon)
(ii) of plant origin (nettle -Urtica, cortex Viburni, herba Polygoni, herba
Arnicae)
-Thrombin is an active compound of the blood coagulation system, is used for
the bleeding from capillary vessels, is applied only topically because if applied
IV can cause thrombosis;
-Fibrinogen is a non-active compound of the blood coagulation system, is
used by IV infusion for the bleeding from bigger vessels, hypofibrinogenemia,
Disseminated Intravasal Coagulation;
Vikasol takes part in sythesis of clotting factors in the liver.
- Etamsylate activates thromboplastin formation on damaged sites of small
blood vessels and decrease prostaglandin synthesis, stimulate platelet
aggregation and adhesion.
-Calcium chloride, Calcium gluconate contain calcium ions which are the
components of the blood coagulation system, stimulate the formation of
active clotting factors, are used parenterally;
Usage: for bleeding, for prophylaxis of bleeding, for decreasing capillary
permeability, for chronic and repeated bleeding, radiation sickness, liver
diseases, overdose of indirect acting anti-coagulants, secondary bleeding due
to thrombocytopenia, prevention of periventricular hemorrhages in
prematurely born children.
Aminocaproic acid and tranexamic acid Fibrinolytic states can be controlled by the
administration of aminocaproic acid or tranexamic acid. Both agents are
synthetic, orally active, excreted in the urine, and inhibit plasminogen
activation. Tranexamic acid is 10 times more potent than aminocaproic acid.
A potential side effect is intravascular thrombosis.
Protamine sulfate
Protamine sulfate antagonizes the anticoagulant effects of heparin. This protein is derived
from fish sperm or testes and is high in arginine content, which explains its basicity. The
positively charged protamine interacts with the negatively charged heparin,forming a
stable complex without anticoagulant activity.
Adverse effects of drug administration include hypersensitivity as well as dyspnea, flushing,
bradycardia, and hypotension when rapidly injected

9c. Pharmacodynamics, mechanisms of action and use of heparin.

Ans:- Heparin is anticoagulant prevent from formation of blood clot.
Antagonist – Protamine sulphate
Pharmacodynamics:
-strong rapid decrease in all stages of blood coagulation;
-increase in platelet aggregation ;also neutralises prostacyclin(potent inhibitor
of platelet aggregation).

-improvement of microcirculation and coronary circulation;

-decrese in inflammation;
-decrease in immunity;
decrease in lipid concentration in blood serum;
-increase the synthesis of surfactant in the lungs;
-decrease in blood pressure;
-decrease glucose level in blood serum;
-increase in diuresis

Mechanism of action: it binds to antithrombin III, causes its conformational

change that leads to the rapid inactivation of thrombin and some other clotting
factors resulting in the inhibition of fibrinogen conversion to fibrin. adminstered
subcutaneous or I.V.

Uses :MI,ischemic stroke, thrombophlebitis,atherosclerosis,autoimmune

disease,acute thombosis and thromboembolism,prevention of thrombus after
surgeries,hemodialysis or blood transfusion

Side effect of heparin – easy bleeding, brushing, bluish color skin , itching of
feet.

10c. Indirect acting anticoagulants: pharmacodynamics, therapeutic use, its

antagonists, prophylaxis of complications.
Ans:- Anticoagulants are drugs decreasing blood coagulation.
*Indirect acting anticoagulants (are active only in vivo)
1) Warfarin ( given orally ,IV or subcutaneous) [ side effect – severe bleeding
, red urine, bloody stool, vomiting of blood , joint pain, severe headache]
2) Ethyl biscoumacetate (Neodicumarinum)
3) Phenindione (Phenylin).

MOA:
 They blocks the enzyme epoxide reductase in the liver.
 The inhibition of this enzyme leads to the block in the creation of
vitamin K active form and the inhibition of the synthesis of clotting
factors.
Pharmacodynamics:
 a decrease in blood coagulation
 an increase in fibrinolysis
 a decrease in lipids concentration in blood
USES: Acute thrombosis (together with or after heparin’s usage), MI ,
Ischemic insult, Thromboembolism ,Thrombophlebitis
,The prevention of thrombus formation after surgeries

Warfarin and related vitamin K antagonists (VKAs) block the function of the vitamin K
epoxide reductase complex in the liver, leading to depletion of the reduced form of vitamin
K that serves as a cofactor for gamma carboxylation of vitamin K-dependent coagulation
factors
Prophylaxis of complication: controlling prothrombin index.

Antagonist – Vitamin K and clotting factors like II, VII, IX and X.

11c. Fibrinolytic drugs: classification, mechanism of action, therapeutic use.

Treatment of complication of fibrinolytic therapy.

Ans: Fibrinolytic drugs: drugs producing the lysis of the blood clot
Classification:
A. Fibrinolytic drugs
Direct-acting – Fibrinolysin Indirect-acting (activators of pro-fibrinolysin)
non-selective – Streptokinase, selective (tissue plasminogen activators, t-PA) – Alteplase –
Tenecteplase
B. Inhibitors of fibrinolysis
Direct-acting – Contrykal Indirect-acting – Aminocaproic acid.

FIBRINOILYSIN is the protein from the donors’ plasma, the active factor of fibrinolysis is administered
by IV infusion has a direct action on fibrin and dissolves fibrin clot in the first hours after thrombosis
is used for the treatment of acute thrombosis, acute myocardial infarction, thrombophlebitis
may cause bleeding resulting from an increase in fibrinolysis, allergy, anaphylaxis, arrhythmia,
hypotension is contraindicated in bleeding, a cerebral vascular accident, recent trauma of the brain,
surgery, uncontrolled hypertension.

STEPTOKINASE is the proteolytic enzyme from hemolytic streptococcus acts indirectly, promotes the
conversion of plasminogen to plasmin, causes systemic activation of fibrinolysis and degradation both
of fibrin and fibrinogen resulting in the dissolving of thrombus has a plasma half-life of 23 min; is
administered by IV infusion (intracoronary infusion in myocardial infarction) is more potent than
fibrinolysin does not cause arrhythmia.

Alteplase (Actilise) is tissue plasminogen activator (t-PA), product of biotechnology; has a half-life of 5
min, is administered by IV infusion; has high affinity for fibrin and acts selectively on plasminogen
bound with thrombus.

Tenecteplase is an enzyme used as a thrombolytic drug; a tissue plasminogen activator produced by

recombinant DNA technology; binds to the fibrin component of the thrombus and selectively converts
thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus; has a
higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor compared to
native t-PA; has plasma half-life of 20-24 min; is administered by IV infusion.
Inhibitors of fibrinolysis are drugs with anti-enzymic activity which decrease fibrinolysis and
proteolysis:

CONTRYKAL is a direct-acting inhibitor of fibrinolysis and proteolysis is administered IV slowly or by IV

infusion binds to plasmin and inactivates it, inhibits the activity of trypsin (fig. 22.8) inhibits fibrinolysis
and stops bleeding caused by the activation of fibrinolysis; inhibits proteolysis and inflammation is
indicated in bleeding resulting from the activation of fibrinolysis; myocardial infarction; acute
pancreatitis; prophylaxis of proteolytic complications after surgeries on the pancreas, the thyroid
gland, the bigger salivary glands, and lungs may cause allergy, nausea, vomiting, hypotension,
tachycardia.

AMINOCAPROIC ACID is an indirect-acting inhibitor of fibrinolysis is administered orally and by IV

infusion, acts during 4-6 hrs, is not metabolized, is excreted with urine interacts with plasminogen and
inhibits its transformation into plasmin, partly inhibits plasmin; inhibits proteolytic enzymes.

12c. Pharmacological properties and use of thyroid gland hormones drugs.

Ans: Thyroid hormones
1. Levothyroxine (L-thyroxine) (T4) - sodium ( L-thyroxine sodium )
2. α-Triiodothyronine hydrochloride (T3) (liothyronin)
3. Thyreocomb: Thyreocomb is combined preparation containing synthetic
thy-roid hormones levothyroxine and lyothyronine together with potassium
iodide.
4. thyreoidine (thyroxin + thriodthyronin)

All taken orally

Pharmacological properties :
An increase in catabolism of proteins, lipids, carbohydrates
An increase in basal metabolism
An increase in body temperature
An increase in the activity of sympathetic nervous system
Participation in growth and mental development in children

Uses: Hypothyroidism (myxedema, cretinism) , Diffuse non-toxic goiter ,

Thyroiditis
Mechanism of action
Most of the hormone (T3 and T4) is bound to thyroxine-binding globulin in the plasma In the
cell, T4 is enzymatically deiodinated to T3, which enters the nucleus and attaches to specific
receptors. The activation of these receptors promotes the formation of RNA and
subsequent protein synthesis, which is responsible for the effects of T4 and hence changing
the function of cells, tissues, organs and systems.

13c. Antithyroid drugs: mechanism of action and use.

Ans:- Anti-thyroid drugs are preparations for the treatment of
hyperthyroidism (thyrotoxicosis, Basedow’s (graves) disease).
METHIMAZOLE (Thiamazole, mercazolil)
Taken orally , concentrates in thyroid gland

MOA:
Blocks peroxidase and suppresses thyroxine’s iodination
A result is a decrease in the synthesis of thyroid hormones and the
reduction of symptoms of hyperthyroidism .

Uses: Hyperthyroidism

Side effects: agranulocytosis, leucopenia, skin rash, fever,

joint pain, thedepigmentation of the hair, paradontitis,
necrotic stomatitis.

IODINE PREPARATIONS Preparations of iodine are used:

–– for the replacement of iodine deficit in hypothyroidism
–– for the prophylaxis of hypothyroidism and goiter
–– for hyperthyroidism (a back-cross decreasing of thyroid
secretion, the decreasing of size and vascularity of
gland.

14c. Comparative characteristic of insulins, its therapeutic use.

Ans:- Classification:
1. Fast acting(begin to work within 5-15 min and active for 3-4 hours) –
Aspart,Lispro, Glulisine.

2. Short-acting(begin working within 30 min and is active about 5-8

hours) –regular insulin, Actrapid, Humulin R, humalog, insul-rapid, iletin.

3. Medium-acting(begin working within 1-3 hrs and is active 16-24

hours) –insuman, humulin N, Protaphane, Monotard.

4. long-acting(begin working within 1-2 hrs and continue to active for 24

hrs) –insulin, glargine
 5. Ultra-long acting(begin working within 30-90 min and continue to be
activefor greater than 24 hrs) – Degludec

6. Combination insulin products(begin toi work with the shorter acting

insulin and remain active for 16—24 hrs) – Novolog Mix 70/30, Novomix 30,
HumalogMix.
Route of administration – SC, IM, IV in hyperglycemic emergency.

Mechanism of action: insulin binds to transmembrane receptors which

activate tyrosine kinase to phosphorylate tissue specific substrates , they acts
by binding to a glycoprotein receptor on surface of cell, receptor consist of an
alpha-subunit, which binds the hormone and a beta subunit, which is an insulin
stimulated, tyrosine specific protein kinase.
Pharmacodynamics: Insulin regulates the protein and carbohydrates
metabolism, lipid metabolism, affects the water-electrolyte exchange; they
have hypoglycemic effect (decrease of glycolysis, gluconeogenesis, increase of
glycogenesis from the glucose in the liver, muscles
Uses : diabetes mellitus type I and type II, diabetes of any type accompanied
by complications (ketoacidosis, infection, gangrene, etc), Diabetic
(hyperglycemic) coma, precoma, surgery +diabetes mellitus, pregnancy +
diabetes mellitus,Gestational diabetes, cachexia, Liver disease, Furunculosis.

Side effect ;- sweating, hunger, fast heart rate, blurred vision, confusion ,
shakiness]
15c. Oral hypoglycemic drugs: mechanism of action, indications to use, side
effects.
Ans:- Oral hypoglycemic drugs are synthetic non-hormonal preparations which
can lower the glucose level in blood.
Classification
1. Sulphonyl urea : Glibenclamide, Glycvidone, Glycolide
2. Biguanides : Metformine
3. Thiazolidinediones (insulin sensitizers) : Rosiglytazone
4. Alpha-glucosidase inhibitor : Acarbose miglitiol,
5. Glinides(Prandial glucose regulators) : Repaglinide
Mechanism of action:
1. Sulphonylurea – increse insulin release from pancrease. Reduce conc. Of
plasma glucagon.

2. Biguanides – increase glycolysis, inhibit hepatic gluconeogenesis,

decrease glucose absorption in GI tract, reduce plasma glucagon level.
Lowering of hyperlipidemia.

3. Thiazolindinediones – increase in the tissue insulin sensitivity.

4. Alpha-glycosidase inhibitor - block alpha-glycosidase of the GIT, disturb

polysaccharides breakdown to monosaccharides and their absorption.

5. Glinides – very rapid onset and short duration of action in stimulating

insulin secretion. Restore insulin secretion pattern at meal
times(prandial phase), without stimulating insulin secretion in the
post absorbtive phase.
Usage : type II non-insulin dependent diabetes in patients after the age of 35
years old.
Side effects : hypoglycemia, meteorism, dairrhea, lactacidosis, increase of
body weight, Anemia, itch, gastrointestinal disturbances.
16c. Glucocorticoids: pharmacodynamics, therapeutic use.
Ans:- Glucocorticoids are adrenal steroids with a prevalent action on
metabolism and inflammation.
Classification:
 Short-acting (8-12 hours): Hydrocortisone acetate (Cortisol)
 Intermediate-acting glucocorticoids (18-36 hours) : Prednisolone ,
Methylprednisolone , Triamcinolone
 Long-acting glucocorticoids (1-3 days): –– Dexamethasone
 Topically active glucocorticoids: Beclomethasone
dipropionate,Fluocinolone acetonide

Pharmacodynamics:
An increase: in protein catabolism, in gluconeogenesis, glucose in blood
The regulation of lipids distribution, an increase in lipolysis
An increase in excretion of potassium and calcium
The suppression of immunity
The suppression of allergic reactions
The inhibition of lymphoid tissue proliferation
An increase in resistance to stress.
Changes in blood film (eosinopenia, lymphopenia)

Therapeutic use:
Substitution therapy of chronic and acute adrenal insufficiency ( hypocorticism,
addisons diseases)
Collagenosis, severe rheumatism, arthritis , arthrosis, Autoimmune diseases,
Hypoglycemic coma, Anaphylactic shock , Allergic diseases of the skin and
mucous membranes , Bronchial asthma

Glucocorticoids effects
1.Anti- inflammatory
2. anti- allergic
3. anti-shock
4. antitoxic
5 immunosupressent

Side effect ;- upset stomach, vomiting, insomnia, depression, heartburn ,

increased sweating] Osteoporosis is the most common adverse effect due
to the ability of glucocorticoids to suppress intestinal Ca2+ absorption,
inhibitbone formation, and decrease sex hormone synthesis.
17c. Complications of glucocorticoid’s therapy, its prophylaxis.
Ans:- Glucocorticoids are adrenal steroids with a prevalent action on
metabolism and inflammation.

Clasification:
(i) Short acting, 8-12hrs-hydrocortisone acetate (Cortisol) use topically
(ii) Intermediate acting glucocorticoids, 18-36-prednisolone[ oral given],
methylprednisolone, triamcinolone [IM given]
(iii) Long acting, 1-3 days- dexamethasone and betamethasone ( IV and IM given)
(iv) Topically active glucocorticoids- beclamethasone dipropionate, flucinolone
acetonide

Complications :
Osteoporosis, hip fracture due to osteoporosis, ecchymosis, peptic ulcer
disease, Cushing’s syndrome, skin thinning and atrophy, acne, mild
hirsutism,facial erythema, impaired wound healing, thinning of hair,
perioral dermatitis.

 Osteoporosis is the most common adverse effect due to the ability of

GC to suppress intestinal Ca absorption,
 inhibit bone formation and decrease sex hormones synthesis. To
prevent this the patient must decrease dose of glucocorticoids, take
calcium and vitamin D supplements.
 The classic Cushing-like syndrome (redistribution of body fat, puffy face,
increased body hair growth, acne, insomnia ,and increased appetite)are
observed.
 Hyperglycemia may develop and lead to DM. Thus patients should
monitor their blood glucose and adjust their medications accordingly.
 Hypokalemia caused by GC therapy can be counteracted by potassium
supplementation.
Long term therapy cause Increased risk of infection, Increased appetite
,Hypertension Peripheral edema, Glaucoma, Hypokalemia, Emotional
disturbances ,Centripetal distribution of body fat ,Increased risk of diabetes.
Glucocorticoids effects:
1. Anti- inflammatory
2. anti- allergic
3. anti shock
4. antitoxic
5 immunosupressent
18c. Withdrawal syndrome in glucocorticoid therapy, its mechanism,
prevention and treatment.
Ans:- Withdrawal syndrome in glucocorticoids therapy is an objective
syndrome resembling true adrenal insufficiency and hypothalamic–pituitary–
adrenal axis suppression
characterized by fever, anorexia, nausea, lethargy, malaise, arthralgias,
desquamation of skin, weakness, weight loss. When glucocorticoids are used at
supraphysiologic doses, glucocorticoid induced hypothalamic pituitary adrenal
axis suppression renders the adrenal glands unable to generate sufficient
cortisol if glucocorticoid treatment is abruptly stopped

Symptoms: such as abdominal pain, chronic fatigue, depression, irritability, or

muscle weakness, nausea, vomiting, anorexia, weight loss, abdominal pain,
diarrhea, general malaise and weakness, lethargy, postural dizziness,
arthralgia, myalgia mood swings, emotional lability.

Signs: postural hypotension, alabaster pale skin (ACTH suppressed), fever

Biochemistry: hyponatraemia, hypoglycaemia, lymphocytosis, eosinophilia.

Mechanism :
Glucocorticoids suppress their own synthesis through a feedback mechanism
that operates at the pituitary (i.e. reduced ACTH synthesis) and the brain
(reduced CRH synthesis), rapid cessation of glucocorticoid therapy leads to
acute adrenal insufficiency, which can be debilitating.
Prevention :
The cessation of high dose, systemic glucocorticoid treatment must be
gradual(not abrupt) to limit acute adrenal insufficiency.
Treatment : Is treated by decreasing the dose of the drug and changing it with
another glucocorticoids like Panangin.
Classification:
(i) Short acting, 8-12hrs-hydrocortisone acetate (Cortisol) use topically
(ii) Intermediate acting glucocorticoids, 18-36-prednisolone[ oral given],
methylprednisolone, triamcinolone [IM given]
(iii) Long acting, 1-3 days- dexamethasone and betamethasone ( IV and IM
given)
Topically active glucocorticoids- beclomethasone dipropionate,flucinolone acetonide
19c. Pharmacodynamics and use of mineralocorticoids.
Ans:- Mineralocorticoids are a class of corticosteroids , are produced in the adrenal cortex and
influence salt and water balances

Drug:
Desoxycorticosterone acetate (IM and sublingual)

Fludrocortisone (orally)

Pharmacodynamics:
-is administered IM and sublingually.
-regulates or enhances reabsorption of sodium from DCT in kidney, decrease
reabsorption of potassium ,.
-regulates fluid – electrolyte metabolism, increases arterial pressure, enhances
muscle work.
-promotes retention of phosphate, calcium carbonate, water and sodium.
-increase the blood pressure, retention of Na,H2O and elimination of K;
-normalization of the tone and improvement of the skeletal muscles activity
Usage: myasthenia; primary and secondary insufficiency of adrenal
cortex (hypocorticism, Addison's disease (chronic adrenal
insufficiency), adynamia.

20c. Oral contraceptives: classification, dosing, side effects.

Ans:- Hormonal contraceptives are hormonal preparations for the prevention
of pregnancy
Classification:
1. Combined(estrogen-progestin): estrogen suppresses ovulation,
2. progestin prevents implantation and makes cervical mucosa impenetrable
to sperms.
(i) monophased- bisecurin, non – ovlon, rigevidon, marvelon,
demulen,Ovidon,Logest;
(ii) biphased- Antiovin, neo-eunomin.
(iii)triphased- Triregol, trisiston, Triquilar.
3. Progestin pills – contain progestin only. Eg. Norethindrone or norgestel.
4. Progestin implants – subdermal capsules (long term contraception),
levonorgestrel, eg. Depo-provera.
5. Postcoital contraceptives – high dose of estrogen or estrogen-progestin
admiistered within 72 hours of coitus. Eg. Postinor.
Side effects: depression; nausea; vomiting; hypertension; breast fullness; acne;
hirutism; skin pigmentation; uterine bleeding; amenorrhea; thromboembolism;
thrombophlebitis, obesity, embryotoxic, teratogenic.

Features of dosing-
1. Discontinuation of all OCs results in fulI return of fertility within 1-2 months.
There may be even be a rebound increase in fertility-chances of multiple
pregnancy are more if conception occurs within 2-3 cycles. With injectable
preparations, return of fertility is delayed. The cycles take several months to
normalize or may not do so at all. They are to be used only if the risk of
permanent infertility is acceptable.
2. If a woman on combined pills misses to take a tablet, she should be advised
to take two tablets the next day and continue as usual. If more than I tablets
are missed, then the course should be interrupted, an alternative method of
contraception used and next course started on the 5th day of bleeding.
3. If pregnancy occurs during use of hormonal contraceptives-it should be
terminated by suction-aspiration, because the risk of malformations, genital
carcinoma in female offspring and undescended testes in male offspring is
increased.

21c. Pharmacology and use of androgens and anabolic steroids.

Ans:-

 Androgens are male gonadal hormones produced mainly by testis or

their synthetic analogues. (administered IM)
 Testosterone propionate
 Methyltestosterone

Testosterone propionate :
takes part in the development of primary and secondary sex characteristics,
maintains fertility in men; has an anabolic action; maintains normal bone
density
uses: hypogonadism in men; combined therapy of certain anemias, wasting
syndromes, senile osteoporosis, severe burns, breast cancer in women before
60

side effects: masculinization in women , altered bone development in children,

the inhibition of gonadotropin release and reduction of spermatogenesis;
 gynecomastia in men, hepatitis, edema

Methyltestosterone is a synthetic analogue of testosterone

Uses: for a long-lasting therapy of male hypogonadism, a pathological climax in

men, impotence connected with the hypofunction of testis, climacteric
disturbances and breast cancer in women;

 Anabolic steroids: are derivatives of androgens with a strong anabolic

effect and residual androgenic activity.
 Methandienone (Methandrostenolone)
 Nandrolone phenylpropionate (Phenobolin)
 Nandrolone deconoate (Retabolil)

Pharmacodynamics
An increase in protein synthesis and mass of skeletal muscles
The retention of nitrogen, phosphor, and calcium
The stimulation of tissue regeneration and hemopoiesis
The improvement in trophy of myocardium
A decrease in glucose level in blood
Uses: Cachexia ,Asthenia Wounds, ulcers ,Bone fractures, osteoporosis ,
Ischemic heart disease ,Myopathy , Diabetes mellitus (additional drug)
Anemia (additional drug) ,Prolonged treatment with glucocorticoids
Side effects: Edema ,An increase in body weight ,Liver disturbances ,
Masculinization in women ( Contraindicated in sportsmen as a
doping.)

22c. Effect of group B vitamins on metabolism and its therapeutic use.

 Vitamin B1: thiamine chloride:
takes part in oxidative decarboxylation of alpha ketoacids, stimulates pyruvic
acid and decrease lactate level. Takes part in carbohydrates metabolism and
stimulates synthesis of acetylcholine.
Used prophylactically in infants, pregnant women, chronic diarrheas,
patients on parenteral alimentation.
Hypovitaminosis of vit b: beriberi disease, polyneuritis, radiculitis, neuralgia, chronic heart failure,
arrhythmia, diabetes mellitus, ulcer of the stomach and duodenum, skin diseases.

Co-carboxylase is active form of b1 used to treat acidosis, diabetes mellitus,

diabetic coma, renal failure, arrhythmia, CNS disease.
  Vitamin B2: riboflavin: coenzymes of Flavin enzymes (FAD, FMN) which
take part in hydrogen ions transport in take part in chain tissue
respiration. Fatty acid oxidation, uric acid formation.
Used in ariboflavinosis, hypovitaminosis (heliosis, glossitis,
photophobia), keratitis, conjunctivitis, skin diseases, radiation sickness,
anemia, asthenia, liver disease, angular stomatitis.
 Vitamin B3: nicotinic acid: Active forms are NAD and NADP. Take part in
electron transport chain in tissue respiration. Participate in synthesis of
amino acid, steroid hormones, bile. Gluconeogenesis, glycolysis.
Used in hypovitaminosis to treat pellagra, hartnup’s disease, diseases of skin
and mucous membrane, liver diseases, atherosclerosis, spasm of blood vessels,
gastritis, gastric ulcer and radiation sickness.
 Vitamin B5: Calcium pantothenate: co enzyme A. participates in the
synthesis of acetylcholine, corticosteroids, metabolism of fatty acids and
citric acid.
Used in neuritis, neuralgia, skin diseases, wounds, burns, allergic
reactions, bronchial asthma, disease of upper respiratory pathways, heart
failure, atonia of intestine, toxicosis of pregnancy.
 Vitamin B6: Pyridoxine hydrochloride: takes part in transamination,
deamination and decarboxylation of amino acids.
Participates in synthesis of dopamine, histamine, serotonin, GABA and
glutamic acid. It promotes the transition of linoleic acid into
arachidonic acid.
Used in hypovitaminosis normochromic microcytes anemia, neuritis,
radiculitis, Parkinson’s disease, epilepsy, chronic alcoholism, liver diseases,
chronic heart failure, gestational toxicosis, anemia, leukopenia, aplastic
anemia, radiation sickness. Prophylaxis and treatment of side effects of
antimycobacterial drugs, hormonal contraceptives and some other drugs
. Side-effects Allergy, A reduce of prolactin secretion.Damage of sensor
nervesand the liver

 Vitamin B9: folic acid: Synthesis of purine and pyrimidine nucleotides,

amino acids and proteins, creatin and methionine.
Additional in treatment of hyperchromic megaloblastic anemia together with
cyanocobalamin.

Used in chronic gastro-enteritis, sprue in pregnancy for prophylaxis of

neurological pathology of the fetus and new born.
 Vitamin B12: Cyanocobalamin: takes part in synthesis of purine and
pyrimidine nucleotides and transforms megaloblastic hemopoiesis into
normoblastic. Takes part in synthesis of methionine, choline, lipid
metabolism.
Used in hypovitaminosis megaloblastic anemia, glossitis, myelosis, radiation
sickness, neuritis, neuralgia, radiculitis, neurological diseases of spinal cord and
brain, liver diseases, hypotrophy in children, stomatitis.
Side-effects Allergy, Hypercoagulation, Tachycardia, pain in the heart,
theaggravation of angina pectoris.
Contraindications Hypersensitivity, thrombosis, thromboembolism. The
drugs hould not be administered together with vitamins B1 and B6 due to
an increase in allergy.

23c. Pharmacodynamics, mechanism of action and use of an ascorbic acid

and Rutin.
Ans:- Ascorbic acid (water-soluble vitamin )is a hexose, easily losses the atom
of hydrogen and transforms into the dehydroascorbic acid.

Moa : The ascorbic acid is a donator and an acceptor of hydrogen. That is why
it takes part in oxidation-reduction systems, is a direct-acting antioxidant

Pharmacodynamics:
 participation in the synthesis: of procollagen and collagen, adrenal
steroids and thyroid hormones , catecholamines
 providing of the growth of bones, the formation of cartilages and
dentine
stimulation of regeneration
 participation in the transformation of the folic acid into the
tetrahydrofolic acid
 increase in the absorption of iron and synthesis of hem
 activation of sympathetic nervous system
 improvement of immunity and phagocytosis
 decrease in the permeability of blood vessels
 participation in cholesterol metabolism and the inhibition of the
develop-ment of atherosclerosis
 detoxication of xenobiotics in the liver
 increase in resistance to stress and radiation

Uses: Hypovitaminosis (scurvy) , Collagenoses ,Rheumatism ,Wounds, bone

fractures , Hemorrhagic diathesis , Atherosclerosis , Radiation sickness ,
Complex therapy of anemia , Infections , Acute and chronic intoxications
Bleeding gums, paradontitis, a complex therapy of severe caries
The stimulation of protective powers of the organism and the improvement of
adaptation

Side-effects only occur in bigger doses of vitamin C:A decrease in the secretion of
insulin, Renal concrements, An increase in BP, decrease in permeability of blood-
tissuebarriers, Hypercoagulation of blood

RUTIN : water-soluble membrane-tropic vitamin, a flavonoid

is an antioxidant; protects the ascorbic acid and epinephrine from oxidation,

participates in oxidation-reduction processes, inhibits hyaluronidase activity,
decreases the permeability of the blood vessels wall

uses: together with the ascorbic acid in vasculitis, hemorrhagic diathesis,

rheumatism, collagenosis, radiation sickness, atherosclerosis, infections,
paradontitis

24c. Biological significance of vitamin E, its therapeutic use.

Ans:- α-TOCOPHEROL ACETATE (anti sterility vitamin) : fat soluble, It belongs
to quinons
Biological significance:
 regulation of reproduction (the promotion of follicles formation and
normal development of pregnancy in females)
 stimulation of spermatogenesis in males
 protects rbc from hemolysis by h2o2 .
 Tocopherol increases the secretion of gonadotropines and sexual
hormones
 the improvement of: skeletal muscles trophy , reological properties of
blood
 an increase in stability to hypoxia
 the stimulation of erythropoiesis and regeneration
 an anti-atherosclerotic, stress-protective, hepatoprotective and cardio-
protective action
 hepatoprotective action from toxic compounds (CCl4)
 Protects PUFA from peroxidation reaction,(hence used in myodystrophy)
 antioxidant (prevent oxidation of vitamin A and carotene)
 Indications : Spontaneous abortions, sexual glands function impairment,
climax
Myodystrophy , Angina pectoris, a omplex therapy of MI,
Atherosclerosis,Liver diseases , Complex therapy of anemia , Diseasesof
blood vessels Radiation sickness ,Stress , Hypervitaminosis D ,
Paradontitis,diseases of the mucous membrane of the oral cavity

Side affects-creatinuria, hepatic disturbance (rarely)

25c. Vitamin A drugs, its pharmacodynamics, use and side effects.

Hypervitaminosis A.

Ans:- Retinol acetate

According to the solubility: fat soluble
According to the biological activity: membrane tropic

 Retinoids :are a class of chemical compounds that are vitamers of vitamin A or are
chemically related to it.

3 generations:
1st generation: (tretinoin (retinoic acid), isotretinoin, and alitretinoin);
2nd generation (etretinate and its metabolite acitretin);
3rd generation (adapalene, bexarotene, and tazarotene).

Pharmacodynamics
 supporting of the normal function of the retina (night vision)
 stimulation of the proliferation and regeneration of the epithelium

 the promotion of growth of the organism, prevention of bones’
epiphyses calcification
 an increase of immunity
 the improvement in the trophy of the myocardium, skeletal muscles,
liver, the nervous system
 supporting of the reproductive function

Pharmacokinetics-metabolized in the liver and excreted with bile and urine, has durative
elimination
Mechanism of actionActive form of retinol is a constituent of visual purple (rhodopsin).It
takes part in the synthesis of keratohyalin.
It takes part in the forming of bones and teeth.
Retinol activates synthesis of immunoglobulins, antibodies, lysosome enzymes.It activates
glycogen deposit in the muscles, heart, and liver.Retinol activates release of STH, thyroid
hormones.It is an antioxidant.
Uses: Hypovitaminosis (hemeralopia) , A therapeutic dose for adult patients is up to
10000 IU per day, a prophylaxis dose is 5000 IU per day (1 drop of 3,44% oil solution
contains 5000 IU)

Eye diseases (cornea and retina diseases)

Hyperkeratosis, leukoplacia , Skin diseases, burns, frostbites
Chronic inflammations of the bronchi, urinary or bile pathways
Rickets (a complex therapy and prophylaxis) , Pregnancy
Diseases of the mucous membrane of the oral cavity, a complex therapy of
severe caries.

Side-effects:
Acute hypervitaminosis: fatigue, headache, sleepiness, nausea, vomiting, pho-
tophobia, convulsions (resulting from an increase in intracranial pressure).
Chronic hypervitaminosis: weakness, fatigue, sleepiness, nausea, skin pigmen-
tation, hyperkeratosis, bone pains, the liver and spleen enlargement

(Contraindications :Acute diseases of the liver and kidney ,Heart failure. )

Retionids
functions throughout the body including roles in vision, regulation of cell
proliferation and differentiation, growth of bone tissue, immune function, and
activation of tumor suppressor genes
uses: inflam-matory skin disorders, skin cancers, psoriasis, acne, photoaging.
They reduce the risk of head and neck cancers. Isotretinoin is used as
chemotherapy for leukemia
side effects: anorexia, skin lesions, hair loss, hepatosplenomegaly,
papilloedema, bleeding, general malaise, pseudotumor cerebri
(hypervitaminosis A syndrome).

*Treatment of hypervitaminosis A: abolishing use , or taking it at very low

doses

26c. Vitamin D drugs, its pharmacodynamics, use and side effects.

Hypervitaminosis D.
Ans:- Drug: Ergocalciferol,Cholecalciferol.
ERGOCALCIFEROL : anti-rachitic effect( ergocalciferol-vitamin D2., Cholecalciferol - vitamin D3)
According to the solubility: fat soluble
According to the biological activity: membrane tropic
Pharmacodynamics
 Main task of vitamin D is to regulate calcium-phosphor homeostasis and
to support calcium level in blood
 an increase in calcium and phosphates absorption from the intestine
and its reabsorption in the kidney
 increase calcium in blood serum and fixation of calcium in bone tissue
under the conditions of the normal calcium level in blood serum, but
stimulation of calcium mobilization from bones if the serum calcium
level is low
 an increase in the calcium influx into nervous cells and into the cells of
skeletal muscles
 the stimulation of immunity and regeneration.
Mechanism of action
Vitamin D penetrates cell membrane, binds to the receptor in cytoplasma and forms the
complex “vitamin D–receptor” .It is transported to nucleus and changes genes expression.
Uses: Hypovitaminosis: the prophylaxis and treatment of rickets, Tuberculosis.
Osteoporosis ,Bone fractures ,Caries, disturbances of teeth forming ,Skin
diseases

Side-effects
*Acute hypervitaminosis: weakness, sleepiness, nausea, vomiting, dyspepsia,
hypotension, arrhythmia, an increase in body temperature, an increase in the
calcium concentration in blood serum, changes in urine (protein, cylinders,
calcium salts, erythrocytes, and leukocytes).
*Chronic hypervitaminosis: bone demineralization, calcium deposit in blood
vessels, the kidney, and other organs (cal-cinosis), CNS damage, heart
insufficiency, an increase in BP, an increase in the calcium level in blood serum
and in urine.

Treatment of D hypervitaminosis
–– Abolishing of drug ,Antioxidants (vitamins E, C, A), Glucocorticoides
–– Other medications: phenobarbital for the intensification of vitamin D
biotransformation; solution of sodium bicarbonate for acidosis; preparations of
potassium and magnesium; calcitrin for the prevention of bone
demineralization
Contraindications-Severe atherosclerosis,Elderly age.
27c. Enzymes and anti-enzymatic medications: pharmacodynamics and use.
Ans:- Enzymes are preparations which play the role of the biological catalyzers of
metabolism in the organism

Enzyme medications :
1)Peptidases and proteases: pepsin, trypsin, chemotrypsin
2)Nucleases: Ribonuclease, desoxyribonuclease
3)Hyaluronidases: Lidase, Ronidase
4)Enzymes of other action: L-asparginase, penicillinase
5)Fibrinolytic enzymes : Fibrinolysin, Streptolyase
6)Combined preparations: Pancreatin, creon, festal,wobenzym

Pepsin : is active in an acidic pH and tears peptide connections and is used to

treat hypoacidic and anacidic gastritis,achilia,dyspepsia
Trypsin : splits peptones that's why they decrease the density of pus and
exudation,improves the clean of wounds and bronchi,decreases edema and
inflammation
*MOA: Pepsin is a stomach enzyme that serves to digest proteins found in ingested
food. Gastric chief cells secrete pepsin as an inactive zymogen called pepsinogen.
Parietal cells within the stomach lining secrete hydrochloric acid that lowers the pH
of the stomach

used to treat purulent wounds, purulent diseases of

thelungs, bronchi, and pleura, osteomyelitis
side effects: disorder of the digestive system. blockage of the stomach or intestine.
gallstones. nausea. diarrhea. high amount of uric acid in the blood. formation of
fibrous tissue in the colon.

Chymotrypsin : similar to trypsin; more stable in body.

Pancreatin : contains amylase,lipase and trypsin; is used orally for replacing
therapy on an insufficient function of the pancreas, anacid gastritis, dyspepsia,
enterocolitis.
Ribonuclease : it restricts RNA to oligonucleotides,that's why they decrease
the viscosity of pus and exudation, improves the clean of wounds and
bronchi,decreases edema and inflammation; is
used to treat purulent wounds,purulent diseases of the
lungs,bronchi,and pleura,osteomyelitis
Desoxyribonuclease is also a nuclease, but its action is connected with the
depolymerization and restriction of DNA.
Lydase : contains hyaluronidase;depolimerazes hyaluronic acid and decreases
the viscosity of connective tissue,increase issues permeability and the
penetration of other drugs.

Ronidase is hyaluronidase preparation; its pharmacological properties are

close to lidase, is only used locally as wet bandages for the treatment of
contractures of joints, scarring, hematoma, chronic tendovaginitis, wounds
that do not heal for a long time.
used to treat contracures of joints,scars after burns and
surgeries,hematomas,chronic inflammation.
Creon is original form of pancreatin. Its capsules contain pancreatin in
minimicrospheres resistant to gastric juice. The drug provides physiological
digestive process and avoids loss of enzyme activity

Anti-enzyme medications :
1) Inhibitors of proteolysis and fibrinolysis : Contrykal, Aprotinin, aminocaproic
acid.
2) Inhibitors of lipases : Orlistat

Contrykal inhibits the activity of trypsin and plasmin, has a direct action on
proteolytic enzymes, decreases proteolysis andfibrinolysis, has anti-
inflammatory properties.
Used in acute pancreatitis, surgeries on the pancreas, lungs, and glands,
bleeding due to an increased fibrinolysis, obstetrics pathology.
Aminocaproic acid (used orally, by IV infusion, and topically (in dentistry); )has mixed
mechanism of action, inhibits proteolytic enzymes, exerts anti allergic and anti
toxic action.
Orlistat inhibits gastric and pancreatic lipases, thud decreasing the breakdown
of dietary fat into smaller molecules that can be absorbed; is used as an anti-
obesity drug.
28c. Lipid-lowering drugs: classification, mechanism of action and therapeutic
use.
Ans:- These are drugs which lower the level of lipids and lipoproteins in blood.

Antihyperlipoproteinemic drugs:
Classification:-
1. -Drugs interfering with intestinal absorption of cholesterol : Polysponinum
,Ezetimibe, Cholestyramine(bile acid sequestrant)
Mechanism of action – binds to bile in acid in intestine, forms insoluble
compounds which are excreted in faeces, loss of bile acid leads to increase in
conversion of cholesterol into bile acids in the liver, reduction in plasma
cholesterol and LDL level.
2. -Inhibitors of de novo cholesterol synthesis:(statins,niacin and fibrate)
fenofibrate, Lovastatin , nicotinic acid, lovastatin, simvastatin, atorvastatin,
rosuvastatin.
Mechanism of action – inhibits HMG CoA reductase and inhibits
cholesterol synthesis.
3. -Drugs increasing cholesterol catabolism by increasing binding of
cholesterol to HDL: Lineatholum, Essentuale, lipostabil.
Mechanism of action – transfers neutral lipids and cholesterol to
oxidation sites, by increasing ability of HDL to bind to cholesterol, protects
hepatic cells, dissolve fat embols.
Used in atherosclerosis with hyperlipoproteinemia 2-4 types.

Anti oxidants a substance that inhibits oxidation

Classification:-
1) Direct acting antioxidants: Tocopherol acetate, Ascorbic acid, Rutin,
Probucol.
Mechanism of action – inhibit oxidation of cholesterol resulting in
ingestion of oxidized cholesterol by macrophages, inhibit conversion of
macrophages into foam cells.
2) Indirect acting antioxidants are ;Glutaminic acid, Methionine, Cysteine.
Mechanism of action – do not interact with free radicals and peroxides,
needed for synthesis of glutathione which supports activity of ascorbic acid.
Usage: treatment of atherosclerosis accompanied by enhanced lipid
peroxidation.
Side effects: edema, cardiac insuffiency, hypertension, hypokalemia,
pulmonary edema, increase BP, cardiac insufficiency.
Side effect ;- hypertension , psychosis, hpyerrnatremia, hypokalemia,
pheripheral edema.

29c. Pharmacodynamics and use of sodium and potassium drugs. Drug-drug

interaction with cardiacglycosides.
Ans:- SODIUM CHLORIDE ( salt)
 ions of Na+ are the main extracellular ions in the body which influence
osmotic pressure,
 electrolyte balance, and volume of circulating blood,
 take part in polarization and depolarization of cell membranes,
 participates in the neu-rotransmission,
 contractions and tone of the muscles, synthesis of hormones

isotonic (0,9%) solution of NaCl: (IV)

uses:treatment of dehydratation in cases of vomiting, diarrhea, intoxica-tions,
hemorrhages, for forced diuresis; is used to dissolve other drugs and to irrigate
wounds, cavities, eyes
hypertonic (2-10%) solution NaCl: has an antiseptic and osmotic action;
uses: topically for the treatment of purulent wounds or administered
IV for the stopping of the lung and stomach bleeding.

SODIUM BICARBONATE ( base/ alkali) Antacid(for peptic ulcer disease)

(Administration :orally, IV, by inhalation, rectally, topically )
 causes the alkalinization of body fluids,
 decreases the acidity
 decreases : the acidity of gastric juice ,acidosis,
 has expectorant, anti-arrhythmic and antihypertensive actions,
antiseptic and osmotic effects (locally)
uses: treat acidosis, hyperacidic gastritis, bronchitis, purulent diseases in the
oral cavity and throat, hypersensitivity of the teeth enamel.
Sodium nitrite,sodium thiosulphate :Antidote for cyanide toxicity , Sodium
stibogluconate(anti protozoan) is a medication used to treat cutaneous,
visceral, and mucosal leishmaniasis, a parasitic infection transmitted by sand-
fly bites
POTASSIUM CHLORIDE
 ions of K+ are main intracellular ions which take part: in polarization
 depolarization processes in cell membranes, neurotransmission,
supporting of the heart rhythm and normal function of skeletal muscles

uses: hypokalemia, arrhythmia, myastenia gravis, acute poisoning with cardiac

glycosides; to prevent hypokalemia caused by some drugs such as
cardiac glycosides, glucocorticoids, diuretics.

Asparkam (Panangin) : is a combined potassium preparation which contains

asparaginates of potassium and magnesium; its properties and indications are
the same as the properties of potassium chloride.

Drug – drug interaction with cardiac glycosides

diuretics: diuretic therapy with digoxin to induce hypokalemia

calcium: synergizes with digitalis
adrenergic drugs: arrythemia
succinylcholine: induce arrythemia
propanolol and Ca++ chanel blockers: depress AV conduction and oppose
positive inotropic effects
metoclopramide, sucralfate and antacids: reduce absorption of cardiac
glycosides
30c. Magnesium drugs, its pharmacodynamics, mechanism of action and use.
Ans:- Magnesium sulfate: ( salt of magnesium) magnesium citrate, magnesium
hydroxide.
IV, IM (after the oral administration acts as laxative)

Moa :is an antagonist of calcium ions in cells

Pharmacodynamics
After parenteral use has sedative, hypnotic and narcosis action,
the inhibition of the vasomotor center;, the dilatation of blood vessels, and a
decrease in BP, the dehydratation of tissues, a, a decrease in intracranial
pressure;
an antidote in acute poisonings with compounds of calcium
action: anti-arrhythmic , anti-seizure , diuretic , spasmolytic action

uses: hypertensive emergency, chronic hypertension, seizures attack, edema

of the brain, tachyarrhythmia, myocardial infarction, toxicosis of pregnancy,
overdose of calcium preparations
Magnesium oxide ( base/ alkali) is taken orally for an antacid action in the
stomach (the antacid effect is without CO2 formation);
Uses : hyperacidic gastritis, may cause a weak laxative action.

Antacid: magnesium hydroxide (symptomatic relief for peptic ulcer,GERD)

31c. Calcium drugs, its pharmacodynamics and use. Regulation of a calcium

metabolism.
Ans:- Calcium drugs:
CALCIUM CHLORIDE
Calcium gluconate
Calcium glycerophosphate
Pharmacodynamics:
Ca++ions regulate the functions of CNS and autonomic nervous system,
stimulate sympathetic activity,
participate in blood coagulation, decrease blood vessels permeability, inhibit
allergic reactions and inflammation,
take part in the formation of bones and teeth
uses:
calcium chloride: hypocalcemia, tetania and spasmophylia, allergic
reactions, in-flammations, bleedings and their prophylaxis, vasculitis, acute
intoxications with fluorides, oxalates, magnesium salts
(administeration IV, rarely is taken by mouth in the form of solution,
in dentistry is used topically (applications, electrophoresis)

calcium gluconate: bone fractures, osteoporosis, to prevent rickets and

osteoporosis under the conditions of immobilization

calcium glycerphosphate: contains calcium and phosphor,

- improves the mineralization of bones and teeth,
- has an anabolic action,
- treatment of bone fractures, osteoporosis.

Calcium metabolism, particularly the levels of Ca found in blood and tissues,

is regulated mainly by three hormones:
(1) parathyroid (PTH) from the parathyroid glands;
(2) calcitonin (CT) from the C cells of thyroid and ultimobranchial bodies,
 (3) dihydroxycholecalciferol (calciferol), formed from vitamin D in liver
and kidney, which increases calcium absorption from the gut.

32c. Steroidal anti-inflammatory drugs: mechanism of action, therapeutic use

and side effects.
Ans:- Classification –
A. Glucocorticoids - (anti shock,anti inflammatory,anti allergy,anti toxic,
immunosuppressive)
1. Short acting glucocorticoids(natural) – hydrocortisone ,
cortisone.
2. Intermediate acting glucocorticoids – prednisone, prednisolone,
methylprednisolone, triamcinolone.
3. Long acting glucocorticoids – betamethasone, dexamethasone.
4. Topical acting glucocorticoids – beclomethasone dipropionate,
budesonide, fluocinolone acetonide, fluocortolone.
B. Mineralocorticoids – Aldosterone,desoxycorticosterone
acetate,fludrocortisone(not used much therapeutically bcz of extreme
salt retaining effect)

Mechanism of action –
They cause induction of annexins in macrophages, endothelium and fibroblasts
which in turn inhibit phospholipase A2 and decreased production of
prostaglandins. Negative regulation of COX-2 which decrease inducible
production of prostaglandins. Negative regulation of genes for cytokines in
macrophages, endothelial cells and lymphocytes which decrease production of
interleukines. They decrease vasopermeability, redness, edema and pain.
Uses – in allergic eye disease, arthritis, arthrosis, bronchial asthma, lupus
erythematous, shock, autoimmune disease, anaphylactic shock, adrenaline
insufficiency.
Side effects – hypertension, glucocorticoid withdrawal, cushing syndrome,
gastric ulceration, increase blood coagulation, edema, increased appetite,
hypokalemia, osteoporosis, hyperglycemia, dystrophy of skeletal muscles.
 Prednisone works as an anti-inflammatory by reducing the swelling and redness of
skin.
  Dexamethasone works by increasing the production of other chemicals that reduce
inflammation.
 Hydrocortisone is a steroid that suppresses the immune system, thereby minimizing
the inflammatory response.

33c. Non-steroidal anti-inflammatory drugs: mechanism of action,

therapeutic use and side effects.
Ans:- Drugs with the prevalence of anti-inflammatory activity are named non-
steroidal anti-inflammatory preparations (NSAIDs)
classification-
Acc. To Mechanism of action –
1. Selective inhibitor of COX – 1 – Aspirin in small dose
2. Selective inhibitors of COX-2 – Celecoxib(highly selective),
Meloxicam(dominant influence), Rofecoxib, nimesulide
3. Non-selective inhibitors of COX-1 and COX-2 –
(i) With peripheral action – Aspirin, Indomethacin, Ibuprofen,
Diclofenac sodium, Piroxicam, Metamizole, Phenylbutazone
(ii) With central action – Paracetamol.

 According to structure grouped into

salicylates, carbonic acids, or enolic acids.

Mechanism of action – inhibition of COX leads to decrease in the synthesis of

prostaglandins which decrease the permeability of blood vessels in the site of
blood vessels.
Inhibition of hyaluronidase activity stabilization of lysosomal membrane
decrease in lysosomal enzyme release which inhibit the activity of leucocyte,
and inhibit energy process in area of inflammation.
Some inhibit fibroblast activity(indomethacin).
Uses – Rheumatism, gout, thrmobophelbitis, Neuralgia, chronic bronchitis,
virla hepatitis, meningoencephalitis, system lupus erythematosus, infectious
allergic myocarditis, rheumatoid polyarthritis, deformating osteoarthrosis,
inflammation diseases of connective tissue, Bechterev’s disease.
Side effects – Peptic ulcer, esophagitis, reversible acute kidney insufficiency,
chronic kidney insufficiency, interstitial nephritis, Nephritic syndrome,
interstitial fibrosis, arterial hypertension, stenocardia, static cardiac
insufficiency, liver insufficiency(increased transaminase level),
thrombocytopenia, hemolytic anemia, granulocytopenia, aplastic anemia,
water electrolyte disorder.
Classification – Acc. To chemical structures:
Salicylates – acetylsalicyclic acid (Aspirin)
Phenyl Acetic acid – Diclofenac sodium
Propionic acid – Ibufrofen, Ketofrofen, Naproxen, Nabumetone
Oxicams – Pyroxicam, Meloxicam, Tenoxicam
Coxibs – celecoxib, Parecoxib, Etoricoxib, Lumaricoxib
Pyrazoles – Metamizoles (Analgin), Phenlybutazone(Butadione)
Fenamtes – Mefenamicacyl
Indole acetic acid derivatives – Indomethacin
Para-amino phenol derivatives – Paracetamol(Acetaminophen)
Sulphonamides- nimesulide

34c. Anti-allergic agents: classification, mechanism of action and use, side

effects.
Ans:- that prevents mast cell release of histamine and formation of other mediators..
Classification:
1.Blockers of H1-histamine receptors :Loratadine,Promethazine,Clemastine;
2.Glucocorticoids : Prednisolone.
3.Selective antagonists of leukotriene receptors : Zafirlucast.
4.Blockers of serotonin receptors : Ciproheptadine
5. Membrane stabilizer only for prophylaxis : cromolyn sodium (used for
prophylaxis of bronchial asthma attack, allergic rhinitis and conjunctivitis),
ketotifen (prophylaxis of bronchial asthma).
Mechanism of action:
1. block H1-receptors due to competitive antagonism with histamine;
2. decrease histamine and serotonine synthesis;potentiate the effect of
catecholamines;inhibit the activity of phospholipase A2;decrease the
amount of leukocytes,eosinophiles,neutrophiles and lymphocytes in the
site of inflammation;
3. It works by blocking the action of certain natural
substances(cysteniel leukotrienes) that cause swelling and tightening of
the airways.
4. block serotonine receptors and decrease production of cytokines
5.block the calcium ions flow into mastocytes inhibiting their
degranulation and, thus ,preventing the realese of allergy and inflammatory
mediators;
Usage : allergic reactions, nettle rash, allergic reactions, anaphylactic shock,
angioneurotic edema, contact dermatitis
Side effects : cardiotoxic effect;inhibition of the CNS;hypotension, decrease
apetite, vomiting, pain in epigastria, blurred vision, tachycardia, headache,
psychosis. Tachyphylaxis, dry mouth.

35c. Antiseptic agents from group of oxidizers and halogens: mechanism of

action and use.
Ans:- Antiseptics act on the surface of the body

1. Halogens: Iodine (5% alcohol solution) , Povidone- iodine,

Ioddicerin ,Chloramine В , Chlorhexidine (Hibitane)

MOA: atoms of halogen intracts with proteins resulting in

halogenization and oxidation of proteins .
It has bactericidal, fungicidal and irritative actions.

Uses:
Iodine: processing of small cuts of the skin , processing of the surgery skin area and
surgeon’s hands , dermatomycoses ,diseases of muscles and joints (the “iodine network” on
the skin).

Povidone- iodine: wounds, ulcers, cuts, burns, vaginitis associated with candidal
 Ioddicerin: skin diseases, ulcers, wounds ,otitis, tonsillitis, chronic atrophic rhinitis,
paradontosis, vaginitis ( due to less irritation on mucous memb)

Chloramine В: disinfection of the environment, clothes, non-metallic instruments

(1-5%); rarely for the treatment of purulent wounds (1-2% solution) and processing of the
skin (0,25-0,5% solution).

Chlorhexidine: wounds, for gargling, prophylaxis of STDI , for the processing of the
surgeon’s hands, the surgical skin area, for a quick sterilization of instruments.

2. Oxidizing agents : Hydrogen peroxide , Potassium permanganate

MOA:
H2O2:
based on the destruction of hydrogen peroxide with the release of oxygen
atoms.
They produce the oxidation and denaturation of proteins
The formation of molecules of O2 results in the foam formation and
mechanical cleaning of the wound

Use:
wounds (3% solution) , impaired skin , capillary bleeding , whitening of
teeth gargling and mouthwash in diseases of the throat and oral cavity
, depigmentation of skin.
The drug should not be used in deep wounds and injures of bigger vessels

KMNO4:
Causes degradation of the molecule of potassium permanganate with the
releasing of oxygen atoms and manganum oxide
Oxygen produces the oxidation and denaturation of proteins resulting in a
bactericidal action.
It also oxidizes some poisons.
Manganum oxide causes an astringent action on the macroorganism.

Uses: irrigation of purulent wounds( 0,1 -0.5% sol)

gargling and mouthwash in diseases of the throat and oral cavity (0,01-0,1%
solution) ,syringing in gynecology and urology (0,01-0,1% solution)
processing of burns (2-5% solution) , the lavage of the stomach in acute
poisoning with morphine, alcohol, alka-loids (0,1% solutions).
36c. Biosynthetic penicillins: antimicrobial spectrum, pharmacokinetics, use
and side effects.
Ans:- Classification
1) short acting : Benzylpenicillin sodium (penicillin G)
Benzylpenicillin potassium , Penicillin V

2) long acting : Penicillin G procaine

(Bicillin-1) : Benzathine benzylpenicillin
(Bicillin-3) : Benzathine benzylpenicillin + benzylpenicillin procaine +
Benzylpenicillin sodium
(Bicillin-5): Benzathine benzylpenicillin + benzylpenicillin procaine

antimicrobial spectrum: narrow: Gram (+) and Gram (-) cocci (streptococci,
some staphylococci, gonococci, meningococci), clostridia, corynebacteria,
listeria, spirochetas, leptospira.

Gram positive microorganism – streptococci, bacillus anthracis, causative agent of tetanus

and gas gangrene, actinomycets, listeria.
Gram negative microorganism – gonococci, meningococci, Moraxella, causative agent of
syphilis, leptospiralis.

Pharmacokinetics
penicillin G: destroyed by gastric juice therefore given IM, IV, endolumbally
is widely distributed through the body
penetrates CNS only in the conditions of meningitis; penetrates placenta
without negative influence on the fetus
is excreted with urine , acts during 4-6 hrs.

Benzylpenicillin potassium not administered IV or endolumbally due to toxic

action of potassium on CNS and the heart.

Bicillin-1 administered only IM once a week for the treatment of chronic

infections (pharigitis, tonsillitis, erysipelas, syphilis, rheumatism) and for
prophylaxis of rheumatism relapse.

Bicillin-3 administered only IM 1-2 times a week to treat chronic infections

(pharigitis, tonsillitis, erysipelas, syphilis, rheumatism).
Bicillin-5 administered only IM once a month to treat chronic streptococcal
and spirochetal infections.

Uses: Infections caused by streptococci (angina, scarlet fever, rheumatism)

Meningitis (caused by Meningococcus) ,Pneumonia (caused by Pneumococcus)
Gonorrhea ,Syphilis ,Gangrene ,Diphtheria ,Infections of the skin and soft
tissues
Listeriosis ,Leptospirosis

Side-effects
Allergic reactions which occur in 0.7-20% of patients taking penicillin and may
range from rash, fever, broncospasm, vasculitis, serum sick-ness, exfoliative
dermatitis, and Steven-Johnson syndrome to anaphylaxis
Neurotoxicity
(Contraindications :Hypersensitivity to penicillin.)

37c. Semi-synthetic penicillins and aminopenicillins: antimicrobial spectrum,

pharmacokinetics,use and side effects.
Ans:- Semisynthetic penicillin – bacteriocidal
There are three categories of semi-synthetic penicillins –
(i) Penicillinase resistant penicillin – Methicillin , Oxacillin, Dicloxacillin.
(ii) Combined penicillins – ampiox, amoxiclav.
(iii) Extended spectrum penicillin –
(a) Carboxypenicillin – carbenicillin, ticarcillin.
(b) Uriedopenicillin – piperacillin, mezlocillin.
(c) Aminopenicillin – ampicillin, becampicillin, amoxicillin.

Aminopenicillin are amine derivatives of benzylpenicillin.

Antimicrobial spectrum – they have broad or wide spectrum of action against
gram+ and gram- bacterias such as staphylococci, streptococci, pneumococci,
(aminopenicillin) haemophilus influenza, whooping cough, gonococci,
salmonella, shigella, Ineffective against pseuudomonas
Pharmacokinetics – they are degraded by gastric juice, oral absorption is
incomplete as food interferes with absorption. It is partly excreted in bile and
reabsorbed, enterohepatic circulation occurs. Primary channel of excretion is
kidney but tubular secretion is slow.
Uses – urinary tract infections, respiratory tract infections, meningitis,
gonorrhea, cholecystitis, septicaemias, surgical prophylaxis, intra-amniotic
infection, mastitis, endocarditis, and pelvic infections.
Side effects – irritation of mucous membrane of digestive tract, dysbacteriosis,
superinfection, pain in injection area, allergic reactions,
granulocytopenia(oxacillin), reduction of platelets aggregation (ampicillin),
disorder of liver function, encephalopathy.
1. Oxacillin : narrow , acid resistant and penicillinase-resistant
effective against Staphylococcus spp.
Oxacillin and other penicillinase-resistant penicillins (meticillin, nafcillin) are only topically
used in the skin infections caused by susceptible organisms. There are nu-merous strains
that are now resistant to these agents - so-called methicillin-resistant staphylococci (MRSA).

2. Ampicillin : wide spectrum ,acid resistant

Gram (-) Haemophilus influenzae, Escherichia coli Proteus mirabilis
destroyed by penicillinase of staphylococci
uses:UTI, respiratory tract infections, and otitis media caused by susceptible organisms

3. Amoxicillin wide spectrum, is an active metabolite of ampicillin,

4. Carbenicillin, piperacillin extended spectrum,

Gram (-) and anaerobic organisms including Pseudomonas spp., Enterobacter spp., and
Proteus spp.; Piperacillin :Pseudomonas and Klebsiella spp. Uses: treatment of infections
caused by susceptible organisms, often associated with bacteræmia and burns. shows the
greatest activity against

5. Ampiox combined preparation (ampicillin and oxacillin), that’s why it has a wide spectrum
and acts on staphylococci.

6. Amoxiclav combined preparation (ampicillin and clavulanic acid) (β-lactamase inhibitor),

Uses: to treat infections caused by penicillin resistant microbes.

Side effects: allergy( rash, fever, vasculitis, bronchospasm , dermatitis)

neurotoxicity

38c. Cephalosporins: classification, antimicrobial spectrum, use, side effects

and complications.
Ans:- Cephalosporins are derivatives of the 7-aminocepalosporanic acid and
contain β-lactam ring.
Classification:
1st generation :- Cefazolin (Kefzol ) , Cephaloridine , Cephalexin
2nd generation :- Cefamandole, Cefuroxime , Cefaclor
3rd generation :- Cefotaxime , Ceftriaxone , Cefixime , Cefazidime ,
Cefoperazone
4th generation :- Cefpirome.

antimicrobial spectrum : Wide except first generation which is narrow

spectrum. and Bacteriocidal

1st generation : Gram (+) cocci including staphy-lococci resistant to penicillins,

Gram (-) cocci, some Gram (-) bacilli. (not effective against MRSA.)

2nd generation : Gram (-) bacilli - Enterobacter, Klebsiella, Haemophilus,

Proteus spp., but they are less active against Gram (+) cocci. Some
preparations (cefoxitin, cefmetazole) are effective against Bacteroides spp.

3rd generation : Gram (+) cocci, Gram (-) cocci, Gram (-) bacilli; they are more
resistant to the effects of β-lactamase.
Ceftazidime and Cefoperazone effective against Pseudomonas.

4th generation : as of 3rd generation, they are also effective against

Pseudomonas aeruginosa and anaerobic bacteria.

Uses:
Severe respiratory infections , UTI , Gynecologic infections , Osteomyelitis
Infections of the skin and soft tissues , -Sepsis , Peritonitis
The prophylaxis of infectious complications of surgeries

Side effects:
Allergy , Dyspepsia , Renal disturbances (cephaloridine)
A decrease in the prothrombin amount in blood
granulocytopenia , Dysbacteriasis (for drugs administered orally).

Complications
Irritation of mucous membrane Of digestive tract ,
infiltrates after i/m introduction
phlebitis after i/v introduction
39c. Carbapenems: classification, antimicrobial spectrum, use, side effects
and complications.
They are a class of Beta lactam antibiotics
Ans:- Classification:
Group 1 – Ertapenem, Panipenem, Tabipenem.
Group 2 – Imipenem, Meropenem, Doripenem, Biapenem.
Group 3 – Tomopenem, Razupenem.
Antimicrobial spectrum – broad spectrum antibiotics or widest spectrum of
antibacterial action. Active against both gram negative and gram positive
bacteria, anaerobes, pseudomonas aeruginosa. They are extremely resistant to the
actions of β-lactamase

USES: UTI, lower respiratory tract infections, gynecological infections, soft

tissue infections caused by susceptible organisms
(Cilastatin inhibits this renal metabolism, promoting renal reabsorption and an extended
half-life of the drug that’s why used with imipenem coz it have short half life)

Side effects: nausea, vomiting, and rarely, seizures in high doses (meropenem
is less likely to cause seizures).

Complications: shortness of breath, pain with urination, pain and swelling of

the skin

Puche toh bolna hai

 Imipenem and Meropenem are carbapenems :act in a manner identical to the penicillins
and cephalosporins Imipenem is given with the agent cilastatin. Imipenem is rapidly
metabo-lised by renal dehydropeptidases. Cilastatin inhibits this renal metabolism,
promoting renal reabsorption and an extended half-life of the drug Meropenem
demonstrates a long half-life with higher blood levels and therefore does not require the co-
administration of cilastatinhave the broadest spectrum of action:

40c. Aminoglycosides: antimicrobial spectrum, use, adverse reactions.

Ans:- these are compounds containing amino sugars joined to a hexose
nucleus in glycosidic linkage .
Classification – 1stgeneration–Streptomycin–
Neomycin–Kanamycin 2ndgeneration–Gentamycin
3rdgeneration–Amikacyn.
Antimicrobial spectrum – they are broad spectrum, bactericidal effective
against most gram negative and few gram positive bacteria. Enterococci,
francisella tularensis, Staphylococci, streptococci, gonococci, pneumococci,
meningococci, brucellosis, tuberculosis, rabbit fever, mycobacterium
tuberculosis. Bacteriocidal (concentration dependent)
Mechanism of action- it binds to 30s subunit,distorting its structure and causing misreading of the mRNA.

Uses – in respiratory infection(postoperative pneumonia), burns, chronic UTI,

infections due to pseudomonas aeruginosa, osteomyelitis, ear infection,
septicemia, meningitis, TB, plague, Tauleremia, pneumonia

Adverse reaction – contraindicated for pregnancy.

(i) Ototoxicity – vestibular or cochlear may be affected.
(ii) Nephrotoxicity – tubular damage resulting in loss of urinary concentrating
power, low g.f.r., nitrogen retention, albuminuria and casts. Aminoglycosides
are concentrated in renal tubules.
(iii) Neuromuscular blockade – they reduce Ach release from motor nerve
ending.
(iv) Hypersensitivity – nausea, vomiting, fever, headache, joint pain, diarrhea,
loss of appetite.

41c. Tetracyclines and Chloramphenicol: drugs, spectrum of antimicrobial

action, use, side effects
Ans:- Tetracyclines contain 4 heterocyclic rings in their molecules

Classification:

1) Short acting – Chlortetracycline, Tetracycline, Oxytetracycline

2) Intermediate acting – Demeclocycline, Methcycline
3) Long acting – Doxycycline, Minocycline
 Natural : Tetracycline
Semisynthetic : Doxycycline , Methacycline

Spectrum of antibiotic – they are broad spectrum, bacteriostatic antibiotics

that inhibit protein synthesis. They are active against gram+ and gram-
bacteria including anaerobes (H. influenza, V. cholera), rickettsiae, chlamydiae,
mycoplasma, spirochetes and against some protozoa.
.
Mechanism of action Tetracyclines are transported into the microbial cell by transport proteins unique to the bacterial
inner cytoplasmic membrane.The drugs bind to 30S ribosomal subunits.They block access of the amino acyl-tRNA to the
mRNA-ribosome complex at the acceptor site and inhibit protein synthesis
They interact with ions of bivalent metals and disturb tissue respiration in microbes; are the antagonists of riboflavin.

Uses:
*Rickettsia infection i.e Rocky Mountain spotted fever, Brill's disease , murine
and scrub Typhus.
* Chlamydial infections (lymphogranuloma venereum, psittacosis, trachoma)
* Mycoplasmal infections
* Bacillary infections (brucellosis, tularemia, cholera, some Shigella and
Salmonella infections)
* Venereal infections
* Amebiasis
* Lyme disease.

Side effects:
Gastrointestinal disturbances , Hepatic dysfunction ,Dermatitis, phototoxicity
Teratogenic action (“tetracycline teeth”)
Yellow-brown discoloration of the teeth and depressed bone growth if
tetracyclines are given to children
A pseudotumor of the brain
Dysbacteriasis and superinfection which can result in staphylococcal en-
terocolitis, candidiasis, and pseudomembranous colitis. Stomatitis, gingivitis.

(Contraindications Diseases of the liver and kidney ,Pregnancy ,Children younger than 8
years old)
CHLORAMPHENICOL
Levomycetin (Chloramphenicol) is a nitrobenzene derivative
Spectrum: Broad
Meningococcus, some strains of Streptococcus and Staphylococcus,
spirochetes, Clostridium, Chlamydia, Mycoplasma; rickettsiae.

Uses: Bacterial meningitis, Anaerobic infections , Rickettsial diseases

Brucellosis ; Infections of the skin and soft tissues Bacterial conjunctivitis ,
Clamidial infections (trachoma).

Side effects: gray-baby syndrome ,Cyanosis, respiratory

irregularities, vasomotor collapse , abdominal distention , loose
green stools , and an ashen-grey color characterize this often fatal
syndrome , Endotoxic reactions , allergy.

42c. Macrolides and azalides: spectrum of action, use. Side effects.

Ans:- Macrolides and azalides are the antibiotics that have a large lactone ring struc-
ture. These may be 14- or 16-membered rings.
CLASSIFICATION:
The 1st generation – Erythromycin
The 2nd generation – Azithromycin – Clarithromycin – Spiramycin.
ERYTHROMYCIN:
Erythromycin is the first generation macrolide.
Pharmacokinetics: is taken by mouth and applied topically (ointment). is destroyed by
gastric juice, that’s why erythromycin doses are given as either enteric coated or as
more stable salts or esters is very rapidly absorbed is diffused into most tissues and
phagocytes; due to the high concentration in phagocytes, it is actively transported to
the site of infection where large concentrations of erythromycin are released during
active phagocytosis is metabolised by demethylation in the liver is excreted with bile
(mainly) and with urine (a small portion) has a half-life of 1,5 hrs.
Mechanism of action:
Erythromycin binds to the 50S ribosomal subunit and inhibits peptidyl transferase
activity. It blocks the translocation of peptidyl-tRNA from the acceptor site to the donor
site. The incoming charged tRNA cannot access the occupied acceptor site, so the next
amino acid cannot be added to the peptide chain. It is usually bacteriostatic, but can be
bactericidal in certain situations. Resistance is connected with the inability of microbes
to take up the antibiotic, decreased affinity of 50S ribosomal subunit for the antibiotic,
and the presence of erythromycin esterase.
Spectrum of action:
Erythromycin has activity against many species of Campylobacter, Chlamydia,
Mycoplasma, Legionella, spirochetes, Gram (+) cocci, and some Gram (-) organisms. Its
antimicrobial spectrum is similar to the spectrum of penicillin. This drug is an alternative
antibiotic to penicillin in patients who are allergic to β-lactam antibiotics
Use: Non-severe infections of the respiratory system, synusitis, otitis Pneumonia due to
Mycoplasma Legionnaires' disease Diphtheria Urogenital infection due to Ureaplasma
Chlamidial infections Syphilis Acne.
Side-effects: Erythromycin has a very low incidence of serious side-effects: Cholestatic
hepatitis, jaundice Epigastric distress Ototoxicity (transient deafness).
Contraindications: 1. The decreased liver function.
Azithromycin is administered orally with bioavailability of 37% due to firstpass-
metabolism; develops maximal concentration in 2,5 -3 hrs, displays tissues
concentration exceeding that in blood plasma in 10- 100 times; concentrates in
phagocytes; has a half-life of 14-20 hrs, is metabolized in the liver; is excreted with urine
unchanged (50%) and in the form of metabolites; has an increased activity compared to
erythromycin; has a broad spectrum of action which is similar to the spectrum of
clarithromycin; does not act on microbes resistant to erythromycin; has indications like
clarithromycin; is well tolerated.
Spiramycin is natural antibiotic, the first representative of 16-member macrolides. It is
administered orally and IV. Absorption for oral administration is incomplete;
bioavailability is 33-39%, reaches high concentrations in the lungs, bronchi, tonsils,
sinuses and pelvic organs of women. An increased concentration is also found in bile,
polymorphonuclear neutrophils and macrophages. Unlike other macrolides, the
metabolism is unrelated to the cytochrome P450 system. 80% of a dose is excreted with
bile. It acts bacteriostatically, but can act bactericidally at high doses: suppresses
protein synthesis in the microbial cell due to reversible binding to the ribosome 50S
subunit. In contrast to the 14-member macrolides has a longer antibacterial effect.
Spiramycin has immunomodulatory properties characterized by an increase in the
neutrophils phagocytic activity, a decrease in the lymphocytes transformation, and an
increase in the production of interleukin-6. The drug is characterized by prolonged post-
antibiotic effect as well as pro-antibiotic effect. Spiramycin is present in the cells in the
active state, as a result of which there is a high clinical effectiveness even in the case of
infections caused by microorganisms that are weakly susceptible to it in vitro –
"spiramycin paradox". Spectrum of action includes: Streptococcus pyogenes,
Streptococcus viridans, Corynebacterium diphtheriae, Staphylococcus aureus,
Streptococcus pneumoniae, Enterococcus, Neisseria meningitidis, Bordetella pertussis,
Campylobacter, Clostridium, Haemophilus influenzae, Neisseria gonor-rhoeae,
Mycoplasma pneumoniae, Chlamydia trachomatis, Toxoplasma gondii, Legionella
pneumophila, Spirochaetes. Indications are toxoplasmosis, bacteria infections (second
line drug) caused by sensitive microorganisms; prevention of meningococcal meningitis
among persons who have been in contact with patients, prevention of acute joint
rheumatism, treatment of bacterial carriage of pertussis and diphtheria. Possible side
effects are nausea, vomiting, diarrhea, allergic reactions, cholestatic hepatitis, acute
colitis, and ulcerative esophagitis.
Clarithromycin is taken by mouth; is absorbed in the gut on 55% that does not depend
on meals, is widely distributed in the body except CNS, is metabolized in the liver with
the formation of active metabolite, is excreted with urine, has a half-life of 4 hrs; has an
increased activity compared to erythromycin; is active against Streptococcus agalactiae,
Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae,
Haemophilus influezae, Neisseria gonor-rhoeae, Listeria monocytogenes, Legionella
pneumophila, Mycoplasma pneumoniae, Helicobacter pylori, Campilobacter jejuni,
Chlamydia pneumoniae, Chlamydia trachomatis, Moraxella catarrhalis, Bordetella
pertussis, Propionibacterium acnes, Mycobacterium avium, Mycobacterium leprae,
Staphylococcus aureus, Ureaplasma urealyticum, Toxoplasma gondii.; is used to treat
bronchitis, pneumonia (including mycoplasmial atypical pneumonia), infections of the
nose, ear, and throat, synusitis, infections of the skin and soft tissues, the eradication of
Helicobacter pylori.

43c. Fluoroquinolones, pharmacodynamics and use.

Ans:- Flourquinolones are fluor-containing quinolones divided into 4 generations
Pharmacodynamics: are administered orally or IV, are widely distributed in the body,
produce high concentrations in the bones, urine, prostate, kidney, are concentrated in
phagocytes and act on intracellular microbes, are excreted with urine or bile, have a
half-life of from 3–8 hrs to 10–20 hrs inhibit the bacterial DNA gyrase (topoisomerase II)
or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription.
First and second generation fluoroquinolones selectively inhibit the topo-isomerase II
ligase domain, leaving the two nuclease domains intact. This modification, coupled with
the constant action of the topoisomerase II in the bacterial cell, leads to DNA
fragmentation via the nucleasic activity of the intact enzyme domains.
Third and fourth generation fluoroquinolones are more selective for the topoisomerase
IV ligase domain, and thus have enhanced gram-positive coverage. the spectrum of
action is wide: Gram (-) bacilli (Enterobacter, Pseudomonas, Haemophilus influenzae,
Moxzarella, Legionella), Chlamidia, Mycobacteria, some Gram (+) cocci. Unlike the first
and second generations, the third gen-eration is active against streptococci. Fourth-
generation fluoroquinolones’ dual action on DNA gyrase and topoisomerase IV
development of resist-ance. Fluoroquinolones can enter cells easily via porins and,
therefore, are often used to treat intracellular pathogens (Lgionella pneumophila and
Mycoplasma pneumoniae)
Use: in urinary tract infections, perioperative antibiotic prophylaxis for transurethral
surgery, gonorrhea, gastrointestinal infections, infections of the bones, joints, skin, and
soft tissues, resistant respiratory infections, tuberculosis (ciprofloxacin, ofloxacin) may
cause nausea, vomiting, diarrhea, pseudomembranous colitis, headache, dizziness,
psychosis, seizures, crystaluria, phototoxicity, cartilage lesions, tendon damage with
spontaneous tendon ruptur

44c. Side effects and possible complications of antibiotics therapy,

their prophylaxis and treatment.
Ans: Side-effects:
Allergy, an anaphylactic shock. For prevention – an allergic test before the first
administration of the drug A direct toxic influence Endotoxic reactions. They display as
an increase in body temperature and intoxication resulting from the liberation of
endotoxins from microbes destroyed by antibiotic Dysbacteriasis. It is the inhibition of
normal microflora in the human body accompanied by activation of Candida fungi. For
prevention – to take antifungal drugs (nystatin, itraconazole) together with a wide
spectrum antibiotics.
Complications:
Hypersensitivity/immune reaction; to antimicrobial drugs or their metabolic
products frequently occur. e.g. penicillins despite their almost absolute
selective microbial toxicity, can cause hypersensitivity problems ranging from
urticaria to anaphylactic shock.
Direct toxicity; high serum levels of certain antibiotics may cause toxicity by
directly affecting cellular processes in the host. E.g. aminoglycosides can cause
ototoxicity by interfering with membrane function in the auditory hair cells.
Superinfection; particularly with broad spectrum antimicrobials/combination of
 agents can lead to alterations of the normal microbial flora of the upper
respiratory tract, oral, intestinal, & genitourinary tracts by permitting the
overgrowth of opportunistic organisms, especially fungi/resistant bacteria.
These infections usually require secondary treatments using specific anti-
infective agent
Drug resistance; it can be of two types:
1) Natural: some microbials are always been resistant to certain antimicrobial
agents, tney lack the target site of metabolic process which is affected by the
drug.
2) Acquired: development of resistance due to prolong usage of antimicrobial
agent. Resistance may be developed by mutation/gene transfer.
Dysbacteriosis; inhibition of the normal microflora in the human body
accompanied by activation of candida fungi.
Prophylaxis:
Antibiotics should be taken with eubiotics if used for long periods of time.
Try using different kind of antibiotics, when treating change from broad to
narrow spectrum as often as possible.

45c. Sulphonamides: classification, antimicrobial spectrum,

mechanism of action.
ANS:- Sulfonamides; belong to folate antagonists. They are synthetic
antimicrobial drugs inhibiting folate synthesis. Sulfonamides are sructural analogs of
para-aminobenzoic acid (PABA)

Classification:
A. Highly absorbed sulfonamides ;
Short-acting – Sulfamethazine (Sulfadimezin) – Aethazolum Intermediate-acting –
Sulfamethoxazole – Sulfaphenoxazole
Long-acting – Sulfamethoxypyridazine (Sulfapyridazinum) – Sulfadimethoxine
Ultralong-acting – Sulfamethoxypyrazine (Sulfalenum)
B. Poorly absorbed sulfonamides – Phthalylsulfathiazole (Phthalazolum)
C. Sulfonamides for a local use – Sulfacetamide sodium (Sulfacylum natrium, Albucid) –
Sulfonamide (Streptocidum)
D. Derivatives of sulfonamide and the salicylic acid or silver – Sulfasalazine
(salazosulfa) – Salazopiridazine – Silver sulfadiazine
E. Combinations of sulfonamides and trimethoprim – Co-trimoxazole (Bactrim)
Spectrum of action:
Sulfonamides have a broad spectrum of action. They are effective against Gram cocci
(Streptococci, Staphylococci), Gram (–) cocci (Neisseria gonorrhoeae), Gram (-) bacilli
(Haemophilus influenzae, E.coli, Shigella, Yersenia enterocolitica, Proteus mirabilis),
Nocardia, Actinomycetes, Chlamidia, Toxoplasma, Plasmodium malariae
Mechanism of action:
Structural similarity to PABA provides competitive antagonism of sulfonamides to PABA
and the blockade of dehydropteroid synthase. This leads to the inhibition of stage I of
the synthesis of the folic acid active form in a microbial cell.
The absence of tetrahydrofolate results in disturbances in the synthesis of nucleic basis
and then in the synthesis of nucleic acids. The reduplication and growth of microbes are
inhibited (bacteriostatic action). Sulfonamides act only on the organisms using PABA in
their life cycle. Sulfas are inactive in the purulent environment rich in PABA. They leak
antimicrobial activity in the presence of ester local anesthetics which are hydrolyzed to
PABA.
The affinity of enzymes to sulfonamides is less than to a natural substance, that’s why a
strike dose of the drug is necessary at the start of treatment. Drugs, inhibiting the
second stage of folate synthesis (e.g. trimethoprim), are synergic to sulfas.
Indications: Respiratory infections Gastrointestinal infections Urinary tract infections
Genital infections (gonorrhea) Trachoma Nocardiasis Toxoplasmosis Infections of the
skin and mucous membranes Infections of the eyes .
Pharmacokinetics:
are taken orally, sometimes are administered IV or applied topically are absorbed in the
small intestine bind to serum albumen penetrate CNS and placenta are metabolized in
the liver: most sulfas undergo acetylation accompanied by a decrease of their solubility
that results in the crystals formation in renal tubuli are excreted the with urine.
Schemes of treatment:
For short-acting drugs: 4 tablets (2,0) for the 1st administration, then 2 tablets (1,0) 4
times a day, after the normalization of body temperature 1 tablet (0,5) 4 times a day
during 3 days. (Total dose is 20-30 g).
For long-acting drugs: 4 tablets (2,0) for the 1st administration, then 2 tablets (1,0)
once a day, after the normalization of body temperature 1 tablet (0,5) once a day during
3 days. (Total dose is 8-10 g)
For ultra-long-acting drugs: 5 tablets (1,0) for the 1st administration, then 1 tablet (0,2)
once a day (Total dose is 2 g). The total dose may be taken once a week.
Side-effects:
Crystalluria Allergy Hemopoietic disturbances Dermatitis and phototoxicity Stevens-
Johnson syndrome Hepatitis Kernicterus (in newborns) Idiosyncrasy (hemolytic anemia
in patients with the deficiency of glucose-6-phosphate dehydrogenase).

46c. Nitrofurans: antimicrobial spectrum and use.

Ans:- It is a drug of urinary antiseptics.

Nitrofurab derivatives- Furozolidone-Nitrofurantoin (Furadonium)

MOA: inhibits carbohydrate metabolism & tissue respiration in
bacteria.
Furozolidone is taken orally 3-4 times a day, is metabolized in the
liver and inhibits liver enzymes, is excreted with urine, disturbs
proton transport during cell respiration.
Spectrum: has a wide spectrum of action: Gram (-) bacilli, Gram (+) bacteria (against
which the drug is less effective), Trichomonas, Lamblia giardiasis

Use: in urinary tract infections, intestinal infections, bacillary dysentery, giardiasis,

trichomoniasis, infected wounds and burns (topically).

Side-effects: allergy, dyspepsia, a disulfiram-like reaction, an increase in BP if the diet

is reach in tyramine.
NIFUROXAZIDE:
is nitrofuran derivative is taken orally every 6 hr, acts in the lumen of the intestine,
because it is practically not absorbed from the digestive tract, is excreted with feces is
effective against staphylococcus, streptococcus, Salmonella, Shigella, Klebsiella,
Escherichia coli, does not affect the composition of normal microflora of the large
intestine, does not cause the emergence of drugresistant strains is used in diarrhea
caused by gram-positive and some gram-negative bacteria, diarrhea caused by food
intoxication, appendicitis, chronic autoimmune gastritis; diarrhea caused by antibiotic
therapy or changes in the natural bacterial flora of the large intestine.
Side-effects: Gi disturbances, elevated liver enzymes, low WBC & platelet count, and
hair loss.

47c. Antituberculosis drugs: classification, mechanism and spectrum of action,

side effects, principles of tuberculosis chemotherapy.
Ans:- Tuberculosis : caused by mycobacterium tuberculosis ( chronic infection )
Classification:-
1. First line with high efficacy and low toxicity - Isoniazid, Rifampicin,
Pyrazinamide, ethmabutol.
2. Second line with low efficacy - Cycloserine, Streptomycin, Ethionamide,
Aminosalicylic acid
1 st line : high efficiency and low toxicity
ISONIAZID(orally, i.m., i.v): ( competes with vit B6, B1, PP)
Mechanism: it disturbs the sysnthesis of mycolic acid (imp constituent of
microbial c.w)
Spectrum: mycobacterium tb *Bacteriostatic: bascilli in stationary phase
*Bactericidal: dividing bascilli
Side effects: Hypersensitivity , Peripheral neuritis (paresthesia) ,Mental
abnormalities, psychotic episodes, euphoria, convulsions ,Optic neuritis,
Hepatitis

RIFAMPIN: (orally or i.v take in empty stomach)

Mechanism: inhibits RNA synthesis by binding with beta subunit of DNA
dependent RNA polymerase
Spectrum: wide spectrum and bacteriocidal ( for both intra /extracellular)
Mycobacterium tb , mycobacterium leporae ( anti leporae)
 Side effect: Red decolourisation of urine, protein urea , rash , GIT Disturbance,
renal damage, hepatic dysfunction
Pirazinamide; (orally )(analog of nicotinamide )( active form-pyrazinoic acid)
Mechanism: inhibition of oxygen dependent mycolic acid synthesis
Spectrum: narrow spectrum ( acts only myco-tb) AND bacteriocidal
Side effect: liver dysfunction , urate retention.
Ethambutol: (orally)
Mechanism: blocks nucleic acids synthesis and inhibits arabinozyl transferases
involved in the synthesis of arabinogalactan, a component of the mycobacterial
cell wall
Spectrum: narrow and bacteriostatic
Side effects: optic neurtitis ( loss of ability to discriminate btw red and blue
colour)
2 nd line : low efficiency and high toxicity
Aminosalicylic acid(orally 10 –15 g per day )
Mechanism: is a competitive inhibitor of PABA in folate metabolism.
Spectrum : Bacteriostatic
side-effects: dyspepsia, crystalluria, the enlargement of the thyroid gland.
Cycloserine: (orally) ( antibiotic)
Mechanism: inhibitor of the cell wall synthesis, is toxic;
Spectrum : Bacteriostatic broad-spectrum
side-effects: CNS and peripheral neurological disturbances.
Ethionamide:
mechanism: structural analog of isoniazid, inhibits acetylation
Spectrum : mycobacteria species
side-effects: hepatotoxicity, gastric irritation, peripheral and optic neuritis.
Streptomycin and Amikacin ( aminoglycoside) (combination drug)
mechanism: inhibitor of protein synthesis,
Spectrum : bactericidal and broad-spectrum antibiotic. It is active against both
gram-positive and gram-negative bacteria
Side-effects : loss of appetite, spinning sensation ( vertigo ), injection site
reactions (pain, irritation, and redness), tingling or prickling sensation in the
face, rash
Fluroquinolones: (combination drug)
Mechanism: inhibits DNA synthesis by blocking DNA gyrase
Spectrum : broad spectrum bactericidal (active against a wide range of aerobic
gram-positive and gram-negative organisms)
side-effects: tendon repture
Principles of tuberculosis chemotherapy:
• To begin the therapy with the 1st line drugs
• To use the 2nd line preparations after the development of drug resistance in
microbes • To apply 2-3 preparations together to delay or prevent the
emergency of resistant strains
• To carry out a long lasting treatment (6-12 months)
• to carry out laboratory monitoring of efficacy of treatment.
There are two phases of chemotherapy
Intensive phase: isoniazid, rifampin, pyrazinamide, etambutol-2 month
Continuation phase: isoniazid, rifampin- 4 month.

48c. Anti-syphilitic agents: pharmacodynamics, mechanism of action,

use.Ans:- Antispirochetal drugs are used to treat syphilis

A. Antibiotics
1. Basis antibiotics : – Benzylpenicillin sodium , – benzylpenicillin (Bicillin-1)
– Benzathine benzylpenicillin + benzylpenicillin (Bicillin-5)

2.Alternative antibiotics : Cefaloridine(cephalosporin) , Erythromycin

(macrolide) Chloramphenicol (Levomycetin)
B. Bismuth preparations
1. – Bijochinol.

Pharmacodynamics : antispirochetal effect

MECHENISM:
Benzylpenicillin sodium , Bicillin-1, Bicillin-5 ( narrow), Cefaloridine(wide):
They are the inhibitor of the cell wall synthesis (inhibit components of
spirochetal cell wall) Narrow spectrum
Uses: Benzylpenicillin sodium for Treponema palidum
alternate antibiotic in syphilis

Erythromycin ( macrlide) , Chloramphenicol (Levomycetin)( wide)

Inhibits the protein synthesis of microbial cell wall
Uses : for treatment of syphilis

Bijochinol: bacteriostatic action on Treponema palidum

MOA: blocks sulphohydryl groups of thiolic enzymes of
the spirochectes and it causes inhibition of their tissue breathing
resulting in death of the cell
uses: is indicated for all stages of syphilis (together with benzylpenicillin),
non-syphilitic encephalitis and myelitis

49c. Classification, mechanism of action and use of antihelminthic drugs.

Ans:- Antihelminthics are drugs that expel parasitic worms (helminths) from the body by
either stunning or killing them. They may also be called vermifuges (stunning) or vermicides
(killing).

Classification:
drugs for treatment of nematodoses :
(i) For intestinal – Pyrantel pamoate, Piperazine adipinate, Levamisole.
(ii)For extraintetsinal – Diethylcarbamazine, Ivermectin

drugs for treatment of cestodoses :

(i)For intestinal - niclosamide
(ii) For extraintestinal - albendazole

Drugs for treatment of trematodoses :

 (i) For intestinal - perchloroethylene
(ii) For extraintestinal - praziquantel, chloxyl.

drugs for wide spectrum of action : praziquantel, albendazole, mebendazole.

Mechanism of action:

(i) mebendazole:- It inhibits the polymerization of helminth tubulin that leads

to inhibiting the synthesis of microtubules in parasitic worms, and
destroying extant cytoplasmic microtubules in their intestinal cells.
 Thus, the drug interferes with microtubule-dependent functions, such as
a glucose uptake.
 The effect takes time to develop and the worms may not be expelled for
several days. The cure rates are 60-100% with most parasites

(ii) Pyrantel,levamisole,aminoacrichine disturb the neuromuscular system

functions in helminths.

(iii) Albendazole, disturb metabolic processes in helminths;

(iv) Praziquantel increase calcium ion permeability of cell membranes of

helminths promoting the incrase of their muscular tone turning into
spastic paralysis.

 Niclosamide – it cause paralysis of muscle of tapeworm and damage

their covering tunics.
Uses :
-Mebendazole: infections causd by pinworm, roundworm, guinea worm, hook
worm, whipworm and trichianasis.

-Piperazine: infections causd by Ascaris lumbricoides and enterobius

vermicularis

-Levamisole: infections causd by round worm, ascaris lumbricoides

-Pyrantel: infections causd by ascaris lumbricoides, enterobius vermicularis,

ancilostoma duodenale, nectar americanus

-Ivermectin: infections causd by Strongiloides stercolaris, wucheri bancrofti,

 roundworm, whipworm

-Niclosamide: infections causd by Taenia saginata, Taenia solium,

Hymenolepsis nana

-Praziquantel: infections causd by Schistosoma japonicum, Schistosomamansoni, schistosoma

haematobium, schistosoma japonicum

-Diethylcarbamazine: filarial infections, whipworm, visceral larva migrans

50c. Antifungal agents: classification, spectrum of action, use, side

effects.
Ans:- Used to treat infection caused by pathogenous fungi (mycoses)
Classification –
1) Antibiotics -

(a) Polyenes
 Nyastatin (Narrow spectrum only used against superficial candidasis),
 Amphotericin B (wide spectrum, Uses = in oral, vaginal and cutaneous
candidosis, systemic mycosis). Side effects = CNS toxicity – headache,
vomiting, nerve palsies. Nephrotoxicity is most common.

(b) Heterocyclic benzofurane: it is fungistatic,

 Griseofulvin (spectrum of action by dermatophytes Microsporon,
epidermophyton) uses= used orally in Dermatophytosis. Side effects –
headache is common, followed by GIT disturbances. CNS symptoms and
peripheral neuritis.

(c) Echinocandins – Caspofungin, Micafungin, Anidulanfungin (narrow

spectrum active against only Candida and Aspergillus.) uses – for deep and
invasive candidiasis also in esophageal aspergillus. Side effects= Rash,
vomiting, dyspnea, hypokalemia and joint pain may occur.
 2) Azoles have wide antifungal spectrum

(i) Imidazoles : Clotrimazole, Miconazole, Ketoconazole(KTZ).

Spectrum – broad spectrum antifungal activity against dermatophytes,
candida, mycosis.
Uses – Athlete’s foot, otomycosiis, all candidosis, dermatophytosis, deep
mycosis.
Side effects = nausea, vomiting, loss of apettite, rashes, hair loss,
headache. Gynaecomastia, hair loss, libido, oligozoospermia may
develop.

(ii) Triazoles : Fluconazole, Itraconazole, Voriconazole

Spectrum – broad spectrum of activity
Uses – cryptococcal meningitis, systemic and deep candidiasis,
candidiasis, pityriasis versicolor, onychomycosis, derma topohytosis.
Side effects – nausea, vomiting, abdominal pain, rashes, headache,
dizziness, pruritus, hypokalemia, neutropenia, anemia.

3) Antimetabolite: Flucirosine ( 5-flurocytosine)

Spectrum = narrow spectrum fungistatic.

MOA-transported to susceptible fungal cells and converted into 5
fluorouracil by deamination,which is a pyrimidine antimetabolite
resulting in inhibition of nuceic acid synthesis
Uses- candida and Cryptococcus infection. Side effects = bone marrow
depression, enteritis and diarrhea.
4) Allylamines : Terbinafine

(narrow spectrum active against canidia and dermatophytes

and fugicidal ).
Uses = dermatophyte infection of toenails and fingernails and other
fungal skin infection.
 Side effects – gastric upset, headache, rashes, taste
disturbance,erythema, itching, deyness, irritation,
urticaria.

51c. Antiviral drugs used to treat influenza, HIV infection, viral

hepatitis.
Ans:-
For Influenza: Amantadine, Remantadine – Ribavirin – Zanamivir and other
neuroaminidase inhibitors.
REMANTADINE:
It is a midantan derivative, structurally related to amantadine. Pharmacokinetics is taken
orally does not penetrate into CNS is excreted by the cells of the epithelium of the upper
respiratory pathways is metabolized in the liver is excreted with urine as a parent drug
and metabolites.
Mechanism of action: The drug blocks the viral membrane matrix protein M2 which
functions as an ion channel (it is required for the fusion of the viral membrane with the
cell membrane). It also inhibits the release of new virions.
Spectrum of action: The virus of influenza A2, the virus of encephalitis. Indications The
treatment of influenza A2 The prevention of influenza The prophylaxis of epidemic
encephalitis.
Side-effects: Headache Hallucinations Ataxia Disturbances of speesh Insomnia Confusion
Seizures.
Amantadine: is structurally similar to remantadine, crosses the blood-brain barrier; does
not metabolized in the body; has antiparkinsonian action; displays side-effects associated
with CNS; should be employed cautiously in patients with psychiatric problems, epilepsy,
cerebral atherosclerosis, renal failure, pregnancy.
Zanamivir (Relenza): is potent and highly selective inhibitor of neuraminidase, the
surface enzyme of the influenza virus which releases viral particles from the infected cell
and speeds up their penetration through the mucosal barrier to other respiratory cells. It
is administered by oral inhalation 2 times a day, has low bioavailability, is precipitated in
the airways at high concentrations, is excreted unchanged by the kidneys for 24 hrs.
Zanamivir acts in the extracellular space, reducing the reproduction of influenza virus, is
used for the treatment and prevention of influenza type A
and B, can cause bronchospasm, skin rash, allergic reactions as side effects.
Oseltamivir (Tamiflu): is a competitive inhibitor of influenza's neuraminidase and
prevents new viral particles from being released. It is taken orally, has bioavailability over
80% and half-life about 1-3 hrs (for its active metabolite T1/2=6–10 hrs), is excreted with
urine as the active metabolite. The drug is used to treat and prevent influenza A and
influenza B, it is recommended in people who are at high risk of complications within 48
hrs of first symptoms of infection. It may cause such side effects as nausea, vomiting.
headache, psychiatric events, seizures, confusion, heart arhythmia, hepatitis and
elevated liver enzymes, rash, allergic reactions, aggravation of diabetes, haemorrhagic
colitis and Stevens–Johnson syndrome.
For HIV infection: Zidovudine and other reverse transferase inhibitors – Sanquinvir and
other HIV protease inhibitors.

ZIDOVUDINE (AZT):
It is a nucleoside analogue (fig. 32.7). Pharmacokinetics is taken orally has bioavailability
of 60% is widely distributed through the body penetrates CNS is metabolized in the liver
is excreted with urine in the form of metabolites has a half-life of 1-3 hrs.
Mechanism of action: AZT is a nucleoside reverse transcriptase inhibitor (NRTI). Its
mechanism of action includes: the phosphorilation of AZT by host cell kinases the
formation of nucleotide analog AZT-triphosphate AZT-triphosphate incorporation into the
growth chain of the viral DNA by the reverse transcriptase the immature chain
termination and inhibition of viral replication . Spectrum of action HIV-1, HIV-2.
Indications: AIDS The prophylaxis of HIV infection through accidental needle stick, The
prevention of vertical HIV transmission from the mother to the neonate.
Side-effects: Anemia, neutropenia GI distress Headache, agitation, insomnia Myalgia
Hepatitis and cholestasis.

Didanosine is used for AZT-resistant HIV-infection.

Zalcitabine is used in a combination with AZT or as monotherapy in patients who can not
tolerate AZT.

HIV PROTEASE INHIBITORS:

Saquinavir, ritonavir, indinavir, nelfinavir, amporenavir belong to this group. Protease
inhibitors act in the stage of late protein synthesis. At this stage, HIV-specific protease
cleaves biochemically inert polypeptides to produce the final structural and functional
proteins of virus. They are used in a combination with AZT, reduce opportunist infections
and prolong the lives of patients.

For Viral hepatitis: Ribavirin

Ribavirin:
is an antiviral medication administered orally. is a prodrug.
Mechanism of action: It is a guanosine analogue used to stop viral RNA synthesis and
viral mRNA capping, thus, it is a nucleoside inhibitor. For the RNA viruses, when ribavirin
is incorporated into RNA, as a base analogue of either adenine or guanine, it pairs equally
well with either uracil or cytosine, inducing muta-tions in RNA-dependent replication in
RNA viruses. Such hypermutation can be lethal to RNA viruses. For DNA viruses, ribavirin
5'-monophosphate inhibits cellular inosine monophosphate dehydrogenase, thereby
depleting intracellular pools of GTP, but the mechanism of ribavirin action on DNA viruses
stays unclear.
Indications: Ribavirin is used primarily to treat hepatitis C and viral hemorrhagic fevers.
For hepatitis C ribavirin is used in combination with pegylated interferon-α. It is the only
known treatment for a variety of viral hemorrhagic fevers, including Lassa fever, Crimean-
Congo hemorrhagic fever, Venezuelan hemorrhagic fever, and Hantavirus infection.
It can be used in the combined treatment of rabies.
Side effects: Feeling tired, headache, nausea, fever, muscle pains, and an irritable mood
Serious side effects include red blood cell breakdown, liver problems, and allergic
reactions. Use during pregnancy results in harm to the embrio and fetus. Effective birth
control is recommended for both males and females for 7 months after use