Somali National University

(Badhan, Putland)
Course Lecturer: Dr Miski Salad Abdulle
Course Title: Pharmacology for nursing I
Academic year: 2023-2024
Nursing batch-7 ( semester 3)
Date: March 09, 2024
Saturday
Unit I: Introduction of Pharmacology
Introduction to Pharmacology

Definition of terms:
Pharmacology: The study of drugs, their physiological
effects, and their clinical uses.
Pharmacology: The study of the manner in which the function
of living system is effected by chemical agents/drugs.
Pharmacology: the study of interaction of drugs with living
organisms. It also includes history, source, physicochemical
properties, dosage forms, methods of administration, absorption,
distribution mechanism of action, biotransformation, excretion,
clinical uses and adverse effects of drugs.
Clinical Pharmacology: It evaluate the pharmacological
action of drug preferred route of administration and safe dosage
range in human by clinical trails.
Drug: a chemical substance used for diagnosis, prevention,
and cure of disease.
Drug: a substance that acts, often by interaction with
regulatory molecules, to stimulate or inhibit, normal
physiological process.
Drugs: are chemicals that alter functions of living organisms.
Drugs are generally given for the diagnosis, prevention, control
or cure of disease.
 Pharmacy: It is the science of identification, selection,
preservation, standardisation, compounding and dispensing of
medical substances.
 Pharmacodynamics: The study of the biological and therapeutic
effects of drugs (i.e, “what the drug does to the body”).
 Pharmacokinetics: Study of the absorption, distribution
metabolism and excretion (ADME) of drugs (“i.e what the body
does to the drug”).
 Pharmacotherapeutics: It deals with the proper selection and use
of drugs for the prevention and treatment of disease.
 Toxicology: It’s the science of poisons. Many drugs in larger doses
may act as poisons. Poisons are substances that cause harmful,
dangerous or fatal symptoms in living substances.
 Chemotherapy: It’s the effect of drugs upon
microorganisms, parasites and neoplastic cells living and
multiplying in living organisms.
 Pharmacopoeia: An official code containing a selected list
of the established drugs and medical preparations with
descriptions of their physical properties and tests for their
identity, purity and potency e.g. Indian Pharmacopoeia (I.P),
British Pharmacopoeia (B.P).
 Drug receptor: specialized target macromolecule in the
cells or cell membrane with which drugs interact to exert
their effects.
 Site of Action: target organ or cellular target of drug action.
 Adverse effect: no drug is free of toxic effects. Side effects
of drug are predictable from a knowledge of pharmacology
of a particular drug e.g. hepatotoxicity and carcinogenesis.
B. Drugs are obtained from:

1. Minerals: Liquid paraffin, magnesium sulfate, magnesium

trisilicate, kaolin, etc.

2. Animals: Insulin, thyroid extract, heparin and antitoxin sera,

etc.

3. Plants: Morphine, digoxin, atropine, castor oil, etc.

4. Synthetic source: Aspirin, sulphonamides, paracetamol,

zidovudine, etc.

5. Micro organisms: Penicillin, streptomycin and many other

antibiotics.

6. Genetic engineering: Human insulin, human growth hormone

Pharmacodynamics
 Is the study of drug effects on the body.
 Pharmacodynamics is the study of the relationship of drug
concentration and the biological effect.
 For most drugs, it is necessary to know the site of action and
mechanism of action at the level of organ, functional system,
or tissue.
Pharmacokinetics
• Is the study of the effect of body on the drug and its
travels through the body.
• To produce characteristic effects, a drug must be present
in appropriate conc. at it’s sites of action (target Tissue) so
that therapeutic effect are obtained.
•Thus, it is important to know the relationship of the
absorption,distribution,binding, biotransformation,
and excretion of a drug and its concentrations and its
locus of action.
Pharmacogenetics
 is the genetic bases for differences among human
population in drug therapeutic response/or toxicity.
 Pharmacogenetics is the application of genomic
information towards the discovery and development of
drugs with new and more specific targets.
 The “idiosyncratic” drug response will increasingly be
predictable, preventable or unacceptable (e.g: considered
malpractice).
Pharmacokinetics
What is Function of Cell Membrane?.
1. Absorption
Absorption (input)
• Is the transfer of a drug from its site of administration
to the blood stream (Systemic Circulation).
• The amount of drug that reaches the systemic
circulation is highly dependent on absorption
especially the route of administration.
• For IV delivery, absorption is complete; that is, the
total dose of drug reaches the systematic circulation
and other routes may result in only partial
absorption. For example, the oral route.
Continue…
 When drug is applied to a body surface (e.g., GIT, skin, etc),
its rate of absorption will determine the time for its maximal
concentration in plasma to produce peak effect.
 Therefore, drug must be absorbed and achieve adequate
concentration at its site of action in order to produce its
biological effects.

A- Transport of drug from the GIT

• Depending on their chemical properties, drugs may be
absorbed from GIT either by passive diffusion or active
transport.
Continue
- Passive diffusion: drug moves from a region of high
concentration to one of lower concentration (Conc. gradient).
- Passive diffusion does not involve a carrier, it is not
saturable, and show low structural specificity.
- Majority drugs gain access to the body by this mechanism.
- Lipid-soluble drugs readily moves across most biological
membranes due to their solubility in the membrane bilayers
such as Anesthetics.
Conti…
 Water-soluble drugs penetrate the cell membrane through
aqueous channels or pores. Other agents can enter the cell
through specialized transmembrane carrier proteins that
facilitate the passage of large molecules (facilitated
diffusion).
 Facilitated diffusion: The molecule to be transported must
first bind to a receptor site on the carrier protein. The shape
of protein then changes, moving the molecule to the inside of
the cell membrane (Channel Proteins).
Conti…
 Does not require energy, can be saturated (the rate of
carrier can’t be increased), and may be inhibited
(glucose).
 In adequate of this protein can cause Diabetes.
 Active transport: drug moves from a region of low
concentration to one of higher concentration (Against
concen. gradient).
 Carrier-mediated active transport is energy-dependent
and is driven by hydrolysis of ATP. This process shows
saturation kinetics for the carrier.
 What is the advantage?. Cell can import or export
specific substrate, regardless extra/intra cellular
Concentration.
Endocytosis and exocytosis
 Endocytosis involves engulfment of a drug molecule by cell
membrane and transport into the cell (large size) by pinching
off drug-filled vesicles e.g: Vit B12, Iron) inside membrane.
 There are three types of endocytosis: All three are active and
require energy in the form of ATP (large volume). Exocytosis,
ejected material may be secratory products such as hormones
and waste products.
B- Effect of PH on drug absorption:
PH Scale
Conti…
 Most drugs are either week acid or week bases. Drugs
passes through membranes more readily if it is
uncharged.
- Ionized (charged) = water soluble
- Non-ionized (uncharged) = lipid soluble
 Week Acid:

 Week Base:
 Physical Factors Influencing Absorption:

-Blood flow to the intestine is much greater than stomach;

thus, absorption is better. Also it has a surface rich in
microvilli; thus, absorption is more efficient. Hence, intestine
is the primary site of absorption for most oral drugs.

-If the drug moves through GIT very quickly, such as Diarrhea,
it is not well absorbed. Presence of food stomach both dilutes
drug and slows gastric emptying.
Bioavailability

Bioavailability is the fraction of administered drug that

reaches the systemic circulation (Target site) in a chemically
unchanged form.

Preparation of same drug by different manufacturers may

have different bioavailability (Original Drug).
Conti…

- Administered dose (orally) does not equal to active form, only

part of the administered dose appears in the plasma.

-Drugs with a low bioavailability may be not active orally such

as Penicillin G is destroyed gastric enzymes or It is not
chemically stable in the PH of gastric contents such as
Insulin.

-First pass hepatic metabolism: When the drug is absorbed

across GIT –> portal vein —>liver –> systemic circulation.
Conti…

Therefore, if drug rapidly metabolism by liver, the amount of

uncharged drug that gains access to the systemic circulation is
decreased (Lidocaine).
- Significant first pass hepatic metabolism limits a drug’s
bioavailability.
- Nature of drug formulation can influence the ease
dissolution and alter the rate of absorption.
First pass Effect
2. Distribution
Distribution
• Distribution is the process by which a drug reversibly leaves
the blood stream and enters interestitium (extracellular fluid)
and/or cells of tissue.
• Delivery of a drug from plasma to interestitium primarily
depends on blood flow, capillary permeability, the degree of
binding of the drug to plasma and tissue proteins, and
relatively hydrophobicity of the drug.
• Blood flow to the tissue is differ widely as result of unequal
distribution of cardiac output to various organs such brain.
Conti…
 Blood flow to the brain, liver, and kidney is much greater
than to the skeletal system.
 High blood flow, together with superior lipid solubility of
thiopental, permit it rapidly move CNS & produce
anesthesia(<1min).
 Capillary permeability: is determined by capillary
structure and chemical nature of drug such as brain,
spleen, and liver.
Conti…
 Brain: endothelium cells are physically jointed and form
continuous wall (blood brain barrier) that prevent many
substance from entering the brain(Lithium & Ethanol).
A specific transporter for the large neutral amino acid
transporter carries Levadopa into brain.
 Placenta: SMW drugs cross placenta ( So Much Win).
Conti…
 Liver: Large fenestrations (slit junction) allow drugs to
exchange freely between blood and interestitium.
 Drug structure: Hydrophobic drugs which have a uniform
distribution of electrons, readily penetrate most of biological
membrane.

Major factors that influence hydrophobic drug’s distribution is

the blood flow to the area.
Conti…
• Hydrophilic drugs, which have either a nonuniform
distribution of electrons, negative or positive charge must go
through the slit junction.
• Plasma albumin maintain the free-drug Conc. as constant
fraction of the total drug in a plasma.
Binding of Drugs to Plasma Proteins
• Plasma albumin is the major drug-binding protein and may
act as reservoir, only unbound drug can distribute into
tissue and exert it is action and is subject to metabolism
and elimination.
• Saturation of binding sites may result in large increase in
unbound drug concentration, which could cause toxicity,
or if albumin conc. is decreased (Hypoalbuminemia), the
dose of highly bound drug must be lowered such as liver
failure & nephrotic syndrome.
Conti…
 Competition for binding sites between drugs and
endogenous substrates can result in interactions and
toxicity.
 Clinical importance of drug displacement

Warfarin + sulfonamide = displacement of Warfarin from

albumin and result of increased therapeutic effect , and
toxic effects such as bleeding.
 3- Metabolism
or
Biotransformation
Introduction
 Main site of drug transformation is liver, kidney, or
other tissues. Body works to convert drugs () to less
active forms and increase water solubility to then
enhance elimination.
 Drug Inactive metabolite(s)
 Drug Active Metabolite(s)
 Prodrug Drug
Drug metabolizing enzymes pathways generally mediate 2
types of reaction.
 Phase I: oxidation, reduction & hydrolysis.
 Drug may be activated (-OH (hydroxide), –NH2 (amino
group) or COOH( carboxylic acid)), unchanged, or most
often, inactivated.

- Microsomal Metabolism:
 Most drugs metabolism are catalyzed by cytochrome P450
system found in endoplasmic reticulam & cell cytoplasm.
CY Substrate Inducers Inhibitors Genetic
P Example Poly-
45 morphis
0 m

1A Theophyline Aromatic Quinolones

2 Acetamenophe hydrocarbons Macrolides NO
n (smoke)

---------

2C Phenoyton General
9 Warfarin Inducers Yes

2D Cardiovascular None known Haloperidol

6 & CNS drugs Quinidine NO
 Cytochrome P450 Isoenzymes

Inducers Inhibitors

Phenobarbital Cimatidine
Phenytoin Macrolides
Carbamazepines Ketoconazole
Rifampin “avirs”
Chronic Alcohol Acute Alcohol
Grape fruit juice*

Grape fruits : Active components inhibit metabolism of many drugs

inlcuding “Statins”.
Conti…
 Nonmicrosomal Metabolism (not involving the P450 system)
 Hydrolysis:
-addition of water molecules to break bonds
-Includes esterases, and amidases
 Monoamine Oxidases:
-Metabolize amine Neurotransmitter
--Endogenous (dopamine, NE & serotonin)
-Exogenous (Tyramine)
• Phase II: conjugation reactions with polar endogenous
substrate e.g: Transferases.
• Types of Conjugation:
– Glucouronide conjugation

– Glycine conjugation = Polar = Inactive

– Sulfate conjugation = water soluble
– Glutathione (GSH)

– Acetylation
• Highly polar drug conjugates may be excreted by the kidney
except Morphine.
Conti…
•Neonates is deficiency this conjugation system (Because of low
level of glucuronosyl transferase).
•If the metabolite from Phase I metabolism is sufficiently polar,
it can be excreted by the kidneys. However, many Phase I
metabolites are too lipophilic to be retained in the kidney
tubules.
•A subsequent conjugation reaction with an endogenous
substrate, such as glucuronic acid, sulfuric acid, acetic acid, or
an amino acid, results in polar, usually more water-soluble
compounds that are most often therapeutically inactive.
 Not all drugs undergo phase I and phase II: Isoniazed is first
aceylated (phaseII) and then hydrolysed to isonicotinic acid
(phase I).
4- Drug Elimination
Drug Elimination

Elimination (out put): drug and its metabolites are removed

from the body via number of routes through kidney into urine,
bile, lungs (anesthetics), skin and mucous membrane
(Rifampicin in tears), intestine, milk in nursing mother, or feces.
 1- Kidney: glomerular filtration: drugs enter the kidney
through renal artery, free drug (not bound to albumin) flows
the capillary slits into Bowman’s space by passive transport
(depend pore size 400-600 angstroms).
 All drugs are filtered at the glomerulus. [Note: Lipid
solubility and pH do not influence the passage of drugs into
the glomerular filtrate].
Conti…
 Proximal Tubular secretion: Drug that were not transferred
into the glomerular filtrate leave glomeruli through efferent
arterioles, which from a capillary plexus surrounding the
nephric lumen in proximal tubule.
 Secretion occurs in proximal tubules by active transport
(carrier-requiring), and shows low specificity, and can
transport many compounds.
Conti…
 Distal Tubular reabsorption: As a drug moves toward the
distal tubule it is conc. increases & exceeds perivascular
space. The drug, if uncharged (Lipid soluble), may diffuse out
of the nephric lumen back into systemic circulation by simple
diffusion.
 This can be minimized, if the goal is to accelerate excretion of
undesirable drug, by increasing ionized from of drug in lumen
(Ion trapping):

A- Weak acid (phenobarbital, Penicillin, salicylic acid) can be

eliminated by alkalinization of such as bicarbonate.
Conti…

B- Weak base (quinine, cocaine, choline), can be eliminated by

acidification such as NH4CL.
 Clinically: elimination rate depends on renal function
(assessed clinically, using serum creatinine levels).
 Abnormality that alter half time of drug, adjustment in dose is
required.
 Which patient Half time of drug is increased?.
 A- Low renal plasma flow or hepatic blood flow such as
cardiogenic shock and heart failure.
Conti…
 B- Decreased extraction ratio (renal disease).
 C- Decreased metabolism (another drug inhibit its
biotransformation (hepatic insufficiency such as Cirrhosis).
 Which patient half time of drug is decreased ?.

A- Increased hepatic flow

B- Increased metabolism (Liver)

C- Decreased protein binding

Well done Guys!.

Conti…
 2-Role of drug metabolism: Most drugs are lipid soluble and
without chemical modification would diffuse out of the
kidney's tubular lumen when the drug concentration in the
filtrate becomes greater than that in the perivascular space.
 To minimize this reabsorption, drugs are modified primarily
in the liver into more polar substances using two types of
reactions:
 Phase I reactions that involve either the addition of hydroxyl
groups or the removal of blocking groups from hydroxyl,
carboxyl, or amino groups, and
Conti…

Phase II reactions that use conjugation with sulfate, glycine, or

glucuronic acid to increase drug polarity. The conjugates are
ionized, and the charged molecules cannot back-diffuse out of
the kidney lumen.
END