Chapter-1

GENERAL PHARMACOLOGY

Supplied by : Binyam Yitbarek

07/29/2025
 Introduction
• PHARMACOLOGY: - Greek: -Pharmacon=drug; Logos= discourse in.
• Pharmacology: - is the science of drugs. It deals with interaction of
exogenously administered chemical molecules (drugs) with living
systems.
• It also includes history,sourse,physicochemical properties,dosage
forms,methods of administration, absorbtion, distribution,
mechanism of action, biotransformation, excretion,clinical uses and
adverse effects of drugs.
• Pharmacodynamics: - is the study of the biological and therapeutic
effects of drugs.i.e ”what the drug does to the body”.
• Pharmacokinetics: - is the study of the absorbtion, distribution,
metabolism and excretion (ADME) of drugs.i.e “what the body does to the
drug”.
• Pharmacotherapeutics: deals with the proper selection & use of drugs for
the prevention and treatment of disease.
• Toxicology: is a science of poisons. Many drugs in large doses can act as
poison. Poisons are substances that cause harmful, dangerous or fatal
sympthoms in living organisms.
SOURCES OF DRUGS

1. Minerals: Liquid parafine, Magnesium sulphate, Magnesium

trisilcate, etc.
2. Animals: Insuline, thyroid extract, heparine, antitoxine sera, etc.
3. Plants: Morphine, digoxine, atropine, castor oil etc.
4. Synthetic sources: Asprine, sulphonamides, paracetamol etc.
5. Micro organisms: Penicilline, streptomycine etc.
6. Genetic engineering: Human insuline, human growth hormone etc.
DRUG NOMENCLATURE

• A drug generally has three categories of names:

1. Chemical name: - describes the substance chemically. E.g. 1-

(Isopropyl amino)-3-(1-naphthyloxy) propane-2-ol.
This is cumbersome and not suitable for use in prescribing.
2. Non-proprietary (generic) name: - It is the name accepted by a
competent scientific body.e.g Mebendazole.
3. Proprietary (Brand) name:-It is the name assigned by the
manufacture(s) and its property or trade mark.One drug may have a
multiple proprietary names.
Pharmacology cont……..
 Drug and medicine
Drug:- a chemical substance of known structure, other than a
nutrient or an essential dietary ingredient, when administered
to living organism, produce a biological effect

Medicine:- a chemical preparation which usually but not

necessarily, contains one or more drugs
Substance that have medical importance or therapeutic
values
Mostly, Drug + additives
Dosage forms
Are d/f preparations of a drug w/h help to facilitate
drug administration & delivery
An ideal dosage form should:
Delivers the right amount of the drug to the right site
Minimizes drug exposure to unwanted sites
Associated with minimal discomfort or inconvenience
Be economical & need lesser expertise knowledge
But there is no such ideal dosage form
Dosage forms cont….
4 types of dosage forms exist
Solid dosage forms
Semisolid dosage forms
Liquid dosage forms
Gaseous dosage forms
 Solid dosage forms
Are those drug preparations which exist as solids
Exist in different forms/preparations
1. Tablets
 Are most common forms of solid dosage forms
 Written as tab or tabs on prescriptions
 Several kinds of tablets are available
 Scored tablets: have indented lines dividing the tabs
 Enteric coated tablets: have special coating material
 Slow release tablets: designed to provide
continuous/sustained release of the drug
 Caplets: oval shaped tablets
 Solid dosage forms cont….
2. Lozenges
 Are sweet tablets containing sugar, water &
flavoring agents
 Are to be chewed/held in the mouth
 Are not swallowed
3. Pellets/beads
 Prepared as sheets or beads for sustained
release of drugs
 e.g. Norplant
Solid dosage forms cont…
4. Capsules
 Written as cap or caps
 Prepared in two forms
 Soft capsules: are made of soft gelatin
 Contain liquid inside & are sealed
 E.g. Vitamin A & E capsules
 Hard capsules: are made of hard gelatin
 Contain two separable pieces or cups
 Contain powder or granules inside
 E.g. Amoxicillin, tetracycline capsules
Solid dosage forms cont…
5. Powders
 Are solid preparations w/h need to be reconstituted
before use
 E.g. penicillin injection
 Semi-solid dosage forms
 Are dosage forms that are too soft to be solid and too hard to
be liquid
 Are mainly used for topical administration
 Includes:
 Creams: are semisolid emulsions of oil & water
water is the main ingredient
E.g. hydrocortisone cream
 Ointments: are semisolid emulsions of oil & water.
 Oil is the main ingredient
 E.g. tetracycline ointment
 Suppositories & Pessaries: used for local effects, for children
& vomiting or unconscious patients
 Liquid dosage forms
 Are found in liquid states
 Can be either clear solutions or suspensions
A. Solutions
 are clear mixtures/fluids
 They don’t need to be shaken/mixed even after long period
of storage
 Are of different forms
i. Elixirs
 are clear solutions w/h contain alcohol & water as solvent
 Also contain flavoring agents
 Are mainly used for pediatric use
 Liquid dosage forms cont…
ii. Syrups
 Are also clear solutions w/h contain water, sugar &
flavoring agent
 They don’t contain alcohol
 E.g. multivitamin syrup
iii. Tinctures
 are clear solutions w/h contain both water & alcohol as
solvent
 But, unlike elixirs, they are used for external use and
don’t contain flavoring agent
 E.g. iodine tincture
Liquid dosage forms cont…
iv. Miscellaneous solutions
 Includes injectable clear solutions, large volume preparations
 E.g. gentamicin injection, glucose preparations

B. Suspensions
 Are not clear liquids
 Contain fine, undissolved drug particles suspended in a
liquid
 Shaking is necessary before use since the solid particles
sediment upon storage
 E.g. antacid suspensions
Gaseous dosage forms
 Contain medical gases & aerosols
 Medical gases:
Are preparations for intrapulmonary administration
Are inhaled through breathing apparatus
The active pharmaceutical ingredient is found as gas or
volatile liquid
 Aerosols:
are another gaseous dosage forms
Contain an active drug suspended in a gaseous vehicle
They are dispersions of solid particles or liquid droplets
in a gaseous vehicle
Do not breathing apparatus
Pharmacokinetics
 Pharmacokinetics:
◦ Pharmaco: drug
◦ Kinetics: motion
 Action of body on drug/ how body handles drugs
 Pharmacokinetics: ADME

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Figure 1.1 Schematic representation of drug absorption,
distribution, metabolism, and elimination.

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1. Absorption
 Process by which the drug leaves the site of administration to
circulatory system

How drugs transfer form site of administration

1. Filtration [aqueous diffusion]
 passage of drugs through aqueous pores.
 Size should be less than size of pore
 has to be water soluble
 Na+, glucose, caffeine
2. Lipid diffusion /simple diffusion
 Drugs supposed to pass through the membrane
 Drugs must be lipid soluble
 High partition coefficient  high absorption

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 Absorption cont’d
3. Carrier mediated absorption
a. Facilitated Diffusion
- passive diffusion but facilitated
e.g. levodopa & amino acid into brain
b. Active transport
- use ATP & carrier proteins
- against the concentration gradient
e.g. levodopa and methyldopa from the gut.

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 Absorption cont’d

4. Phagocytosis & pinocytosis

- Process by which large molecules are engulfed by the cell
membrane forming a vesicle & releases them
intracellulary.
- E.g. protein, toxin

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 Simple
Cxs Facilitated Active transport
diffusion

Incidence commonest less common least common

Process slow quick very quick

Movement
along the conc. along the conc. against conc.
gradient gradient gradient

Carrier not needed needed needed

Energy not required not required required
Routes of Administration
 Enteral
◦ Oral, rectal, sublingual, buccal
 Parenteral
◦ Intramuscular, subcutaneous, intravenous, intra arterial
 Inhalation
 Topical

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Figure 1.2 Commonly used routes of drug administration. IV =
intravenous; IM = intramuscular; SC =subcutaneous.
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Drug Absorption of Various
Oral Preparations
Liquids, elixirs, syrups Fastest
Suspension solutions ê
Powders ê
Capsules ê
Tablets ê
Coated tablets ê
Enteric-coated tablets Slowest
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Factors affecting GI absorption
 Physicochemical ppt of  Formulation
the drug
◦ Molecular size, shape, lipid
 Gut motility
solubility, partition coefficient,  Blood flow to the site of
pH of media & pKa of the
absorption
drug)
 Area of absorbing surface  Gastric secretion
& contact time
 Drug interaction
 Route of Admn.

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 Bioavailability
 Bioavailability: fraction of administered drug that reaches the
systemic circulation
◦ Amount of drug available in the circulation/site of action
◦ Bioavailability is expressed in percentage
◦ Bioavailability is 100% for drugs given IV.

Factors affecting bioavailability

◦ Extent of absorption
◦ Route of Admn.
◦ First pass effect
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2. Drug distribution
 Process by which a drug reversibly leaves the blood
stream & enters the interstitial and/or cells of the tissues
Factors affecting drug distribution
1. Plasma protein binding
◦ Albumin= [acidic drugs]
◦ -glycoprotein = [basic drugs]

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Drug distribution cont’d
2. Tissue uptake of drugs
- Adipose Tissue [DDT]
- Bone [TTC]
- Liver [chloroquine]
- Thyroid Gland [iodine]
3. Barriers
 Blood brain barrier & Placental barrier
4. Rate of blood flow
 Brain, kidney, liver & lung- highly perfused

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3. Biotransformation/metabolism
 Alteration of drug structure- w/c may result in ;
 inactivation
activation (prodrug) of the drug.
Activation from another active drug

 Main site of biotransformation

◦ Liver, intestine, plasma

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Biotransformation/metabolism
 TWO PHASES OF BIOTRANSFORMATION
Phase I biotransformation
 Consists of reactions:
◦ Oxidation [Ethanol]
◦ Reduction [Estrone]
◦ Hydrolysis [Procaine]

 The products are more reactive than parent drug

 Purpose of phase I reaction is to introduce functional groups; [NH2,

thiol, hydroxyl]
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 Biotransformation cont’d

Phase II reaction [Conjugation]

 Conjugating compounds include:
◦ Glucoronide[CAF, Morphine, sulphonamide, ASA]
◦ Acetyl [INH, hydralazine]
◦ Sulphate [steroids]
◦ Methyl [catecholamine]

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 Biotransformation cont’d

 Enzymes Responsible for Metabolism of Drugs;

 Microsomal Enzymes

 present in the smooth endoplasmic reticulum of the liver,

kidney, and GIT. E.g. glucuronyl transferase,

dehydrogenase, hydroxylase, CYP450 etc...

 Non-microsomal Enzymes

 present in the cytoplasm, mitochondria of different

organs. E.g. Esterase, amidase, hydroxylase etc...

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 Biotransformation cont’d

 Enzyme induction

◦ Phenobarbitone: nonselective

◦ DDT: induces CYP1A1

 Enzyme inhibition

◦ Cimetidine -Ketoconazole

◦ Erythromycin -chloramphenicol

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 Biotransformation cont’d

Consequences of drug biotransformation

 Activation [L-dopa  dopamine]
 Maintenance of activity [diazepam  oxazepam]
 Inactivation [Phenobarbital  hydroxypentobarbital]

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 First-Pass Effect
 The metabolism of a drug and its passage from the
liver into the circulation.
◦ A drug given via the oral route may be extensively metabolized by the liver
before reaching the systemic circulation (high first-pass effect).

◦ The same drug—given IV—bypasses the liver, preventing the first-pass

effect from taking place, and more drug reaches the circulation.
 First-Pass Effect
• Routes that bypass the liver:
◦ Sublingual ◦ Intravenous
◦ Transdermal ◦ Intramuscular
◦ Buccal ◦ Subcutaneous
◦ Vaginal ◦ Intranasal
◦ Rectal* ◦ Inhalation

*Rectal route undergoes a higher degree of first-pass effects

than the other routes listed.
Pharmacokinetics
Half-Life
 The time it takes for one half of the original amount
of a drug in the body to be removed.
 A measure of the rate at which drugs are removed from the
body.
 Read About
◦ Volume of Distribution
◦ Clearance
4. Excretion of drugs
 Transportation of unaltered or altered form of a drug out of the
body
 Minor route of excretion
◦ Eye, breast, skin
 Intermediate route
◦ Lung [Volatile]
◦ Bile [Digoxin, Rifampin]
 Renal excretion- major route for most drugs & involves
◦ Glomerular filtration
◦ Active tubular secretion
◦ Passive tubular reabsorption

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PHARMACODYNAMICS
 The study of drug effects on the body.
 A fundamental principle is that drugs only modify underlying
biochemical and physiological processes; they do not create
effects de novo.

Site of drug action

 A drug may act:
• Extracellularly eg..Osmotic diuretics.
• On the cell surface eg. Digitalis, Penicillins, Catecholamines.
• Inside the cell eg. Anticancer drugs, steroid hormones.
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Mechanisms of drug action
The fundamental mechanisms of drug action can be distinguished in to four
categories.

1. Physical action:
• Physical property of the drug is responsible for its action. Eg. Osmotic activity-
magnesium sulphate.

2. Chemical action:
• The drug acts according to simple chemical equation. Eg. Antacids neutralize gastric
HCl.

3. Through enzymes:
• Enzymes are very important sites of drug action. Drugs can either
increase or decrease the rate of enzymatically mediated reactions;
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4. Through receptors:
 Most drugs act by interacting with cellular components called
receptors.
 Receptors are protein molecules present either on the cell
surface or with in the cell.
 eg. Adrenergic receptors, cholinoceptors, insulin receptors.

 A drug which is able to fit on to a receptor is said to have

affinity for that receptor.

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4. Through receptors (CONT’D):
 When a drug is able to stimulate a receptor, it is known as an
Agonist.
 An agonist has both an affinity and intrinsic activity/efficacy
 Antagonist has affinity but not efficacy or intrinsic activity.

 Efficacy is the maximum response produced by a drug.

 When a drug blocks a receptor, it is known as antagonist and
therefore blocks the action of the endogenous transmitter .

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 Factors that modify drug effect & drug dosage

 Sex
 Body weight: lean/obese  Physiological variables:
◦ fluid & electrolyte
 Age:
◦ child (plasma protein binding,  Pathological factor (kidney &
incomplete dev’t of BBB, liver diseases)
Underdeveloped renal & enzyme
 Genetic makeup:
system)
◦ fast & slow acetylation of INH
 Food
 Tolerance to drug
 Route of administration
 Drug interaction

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 Dose calculations
Fried’s Rule
Infant’s age (in month)
x
Average adult dose
Infant’s dose (<1year)
=
150 months

Young’s Rule
=Child’s age (in Years)
Child’s dose (1-12year) xAverage adult dose
Child’s Age (in years) + 12
 Dose calculations
Clark’s Rule

Child’s dose
= xAverage adult dose
Weight of child (in pounds)
150

=Weight of child (in Kg)xAverage adult dose

Child’s dose
70

Surface Area Rule

S.A of child (in square meters)
x
Child’s dose= Average adult dose
1.73
Types of Receptor Antagonism

1. Reversible Antagonism
◦ Competitive antagonism
◦ Non-competitive antagonism

2. Irreversible Antagonism

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1. Reversible Antagonism
◦ weak bond

I. Competitive Antagonism:
◦ Same site
◦ Antagonist doesn’t produce effect, but  apparent potency of
agonists.
◦ Surmountable (overcome by increasing agonist
concentration)
◦ Dose-response curve shifts to the right

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Effect of competitive antagonists on dose-response curves

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1. Reversible Antagonism

II. Non- competitive antagonism

◦ Binds to the receptor at different site from the agonist
◦ Insurmountable (Can not be overcome by increasing
agonist concentration)
◦ Such competition decreases the maximal response

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Effect of non-competitive antagonists on dose-response
curves
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2. Irreversible antagonism

 Covalent bond
 Irreversibly inactivate the receptor
 Insurmountable
 Shits the dose-response curve to the right and
decrease the maximal response

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Drug interaction: classification
 Pharmaceutical: Diazepam in infusion fluid: precipitation
 Pharmacokinetic
◦ Absorption (TTC & milk, TTC & oral iron preparations)
◦ Biotransformation
 Induction (Phenobarbitone & Warfarin)
 Inhibition (Cimetidine ,Warfarin)
◦ Excretion (Probenecid & Penicillin)
 Pharmacodynamic: interaction of drugs that occur on the
receptors or on the effects of a drug.

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 Types of pharmacodynamic drug interaction

 Additive[1+1= 2] E.g. Carbachol + Acetyl choline

 Synergism[1+ 1> 2]E.g. Trimethoprim + Sulphemethoxazole
 Potentiation[0+1 > 1] Isopropanol + Carbon tetrachloride
 Antagonism[0+1< 1]
◦ Physiological antagonism (Insulin & Glucagon)
◦ Chemical antagonism (Amino glycosides + Penicillin)
◦ Pharmacokinetic antagonism (Enzyme
inducers/inhibitors)
◦ Pharmacological (Receptor) antagonism

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Pharmacodynamics
Drug actions:
 The cellular processes involved in the drug and
cell interaction

Drug effect:
 The physiologic reaction of the body to the drug
Pharmacodynamics
Onset
 The time it takes for the drug to elicit a
therapeutic response

Peak
 The time it takes for a drug to reach its maximum
therapeutic response

Duration
 The time a drug concentration is sufficient to elicit
a therapeutic response
Adverse drug reaction
 ADR: defined as any response to a drug that is noxious and
unintended that occurs at doses used for prophylaxis, diagnosis
or therapy.
 Types of ADR:
◦ Predictable: arise from known pharmacological property of
the drug. E.g.- side effect & toxic effect
◦ Non predictable: allergy & idiosyncrasy
 adverse drug reaction that occurs in a small number of persons and
no correlation to dosage

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 Adverse drug reaction

1. Side effects: are pharmacological effects produced with

therapeutic dose of the drug
E.g. dryness of mouth with atropine and useful when used as
pre-anesthetic medication
2. Toxic effect: excessive pharmacological action of the drug due
to over dosage or prolonged use.

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 Adverse drug reaction
3. Untoward/ Secondary effects: indirect consequences of primary
action of drug,
◦ e.g. suppression of bacterial flora by tetracycline paves the
way for superinfection;
◦ corticosteroids weaken host defense mechanisms and latent
tuberculosis gets activated.
4. Idiosyncratic reaction:
 Genetically determined ADR, could be:
◦ dose related [neuropathy by INH] or
◦ Dose unrelated [hemolytic anemia by primaquine, sulphonamide,
dapsone]
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 Adverse drug reaction
5. Hypersensivity reaction/ allergy:
◦ Type I(Anaphylactic reaction):
 Antigen + IgE on basophile/mast cell
 Anaphylaxis, asthma, hay fever or urticaria
◦ Type 2(cytotoxic reaction): antigen + IgM/IgG
 Penicillin binds RBC evokes production of antibody and lysis
◦ Type III (immune complex mediated reaction): skin rashes
due to NVP.

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 Adverse drug reaction

6. Teratogenic effect: the effect of drug to cause

fetal abnormalities when administered to the
pregnant mother.
◦ E.g. thalidomide cause phocomelia [absent or grossly
abnormal limbs]

7. Carcinogenicity and mutagenicity: a drug to

cause cancer and genetic defects respectively.

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 FDA Use-in-Pregnancy Ratings of drugs

CATEGORY INTERPRETATION

A Adequate, well-controlled studies in pregnant women have

not shown an increased risk of fetal abnormalities to the
fetus in any trimester of pregnancy.
B Animal studies have revealed no evidence of harm to the
fetus, however, there are no adequate and well-controlled
studies in pregnant women.
OR
Animal studies have shown an adverse effect, but adequate
and well-controlled studies in pregnant women have failed
to demonstrate a risk to the fetus in any trimester.

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 FDA Use-in-Pregnancy Ratings of drugs
CATEGORY INTERPRETATION

C Animal studies have shown an adverse effect and there are no adequate
and well-controlled studies in pregnant women.
OR
No animal studies have been conducted and there are no adequate and
well-controlled studies in pregnant women.
D Adequate well-controlled or observational studies in pregnant women
have demonstrated a risk to the fetus. However, the benefits of therapy
may outweigh the potential risk. For example, the drug may be
acceptable if needed in a life-threatening situation or serious disease for
which safer drugs cannot be used or are ineffective.
X Adequate well-controlled or observational studies in animals or
pregnant women have demonstrated positive evidence of fetal
abnormalities or risks. The use of the product is contraindicated in
women who are or may become pregnant.
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xamples of drugs in each category;

 Category A: MgSO4, thyroxine, Paracetamol

 Category B: Penicillin V, Amoxacillin, Paracetamol, Lignocaine
 Category C: Morphine, codeine, atropine, Corticosteroids,
adrenalline
 Category D: Aspirin, Phenytoin, carbamazepine, lorazepam
 Category X: Estrogens, ergometrine

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Exercises
 A 3 year old child having body weight of 30 pound
requires to administer drug. The adult dose is 100mg.
Calculate the dose required for the child.
Dose-response relationship
 Pharmacological responses can be:
1. Quantal Response
2. Graded Response
1. Quantal Response
 All or none phenomena
 Used for Population (to study toxicity)
 the X-axis of dose-response curve represents dose of a
drug and Y-axis percent responding.
◦ Examples include death, pregnancy, cure, pain relief, liver
toxicity, sleep induction etc
2. Graded Response
 Dose of a drug and response are related
proportionally. i.e. the more drug is given the more
response is achieved.
 Infinite number of intermediate states
 Used to study response of a drug in an individual
◦ Examples include a change in heart rate or systemic blood
pressure.
 Dose-response Curves
 Dose-response curves exist for graded type of responses.
 Dose-response curves are presented by:
1. Hyperbolic curve
2. Sigmoidal curve
1. Hyperbolic Curves
• A curve obtained from dose-percent response plot.
• Linear relationship exists at lower dose.
2. Sigmoidal Curve
• Log dose-percent response plot
• Sigmoid or S-shape with linear portion in the middle
 Maintenance Dose:
 Loading Dose:
 Median Effective Dose (ED50%)
 Median Lethal Dose (LD50%)
 Therapeutic Index
Therapeutic Index
 Used to predict drug safety
 It considers the dose required for a toxic effect versus

that required for the desired beneficial effect

 In general, a larger T.I. indicates a clinically safer drug
Development and evaluation of new drugs

 Two steps:
◦ Preclinical development
◦ Clinical development
 Phase I
 Phase II
 Phase III
 Phase IV