Introduction

to
Pharmacology
Dr. Ahmed.H.Elbanna
Assistant professor of Pharmacology & Toxicology
 Pharmacology
■ Definition:
is the science which deals with drugs
■ Drugs:
Are chemical substances which increase or
decrease the functional activity of a cell, but do
not create a new function
■ Sources of Drugs:
1) Inorganic: ● Iron, Mg

2) Organic: (A) Animal origin ● Insulin ● Heparin

(B) Plant origin ● Atropine ● Morphine
3) Synthetic: ● Sulphonamides

4) Microorganisms: ● Penicillin ● Streptomycin

Drug nomenclature (drug names )

Chemical name : the name used by chemist ( N-acetyl-p-

aminophenol ).

Generic name : paracetamol.

Trade name :Panadol and each company has its specific name.
 Drug are used in
 Treatment of diseases as therapeutic agent (
antibacterial) .

Prevention of diseases as prophylaxis ( hyoscine in

motion sickness ).

Diagnosis of diseases ( dye in radiography ) .

Prevention of normal biological function (contraceptive

).

Control disease like Diabetes .

Main processes involved in drug
therapy :

• Pharmaceutical process
The active ingredient obtained from any source should be put in proper dosage
to be absorbed.

• Pharmacodynamics
The effect of drug and it is adverse effect

Include Mode of action, pharmacological effect ( desired or not desired )

• Pharmacotherapeutic
The use of drug in diagnosis, prevention and treatment of diseases.
• Pharmacokinetics
What the body does to the drug

• Absorption – distribution – metabolism – excretion.

Part I: Pharmacodynamics (PD)

■ Definition:

Study of drug action and mechanism of action on

the cell function(Effect of the drug on the
body)
DRUG

Drug
BODY
 I. Types of Pharmacodynamics
effects (mechanism of action)

1- Local action • Before it enters

circulation

2- Systemic action • After it enters circulation

3- Reflex (Remote) • On remote site of action

as Camphor (S/C)

• On specific site of
4- Specific action action as Digoxin on
heart
II- General MOA of pharmacodynamics effects of
drugs

• Mechanical: e.g. Liquid paraffin (constipation).

• Physical:
i. adsorption e.g (Kaolin in diarrhea).

ii. osmosis e.g. (Magnesium sulfate in constipation).

• Chemical: neutralization e.g. (Sodium

bicarbonate in hyperacidity).
 Cont. II- General MOA of pharmacodynamics
effects of drugs

• By replacement: e.g. Vitamins and hormones.

• By chelation: e.g. BAL for mercury poisoning.
(Dimercaprol, also called British anti-Lewisite)

• By binding to the cell receptors: (Cell Receptor

Theory ).

• Interfere with cell division e.g. cytotoxic agents.

 Cell Receptors
■ Cell receptors:
 Chemically reactive proteins found on cell membrane
( extracellular ) or in cytoplasm or nucleus ( intracellular ).
 The drug can bind to its receptors and so initiate an effect
(response).

Ka Affinity Drug Efficiency

D+R D/R complex Response
Kd

Ka = Association constant Kd = Dissociation con.

 Types of receptor and signal transduction
1- ligand gated receptor:
 they are membrane receptors, located on the gate of ionic channels.
 drug/receptors complex will change cell membrane permeability to
ions.
• Very rapid (few milliseconds) (rapid onset and short duration).
• A.ch which binds to nicotinic receptors on neuromuscular junction,
opening of Na+ channels on skeletal muscles Na+ influx
generation of action potential (depolarization) contraction of
skeletal muscles.
Cont. Types of receptor and signal transduction
2- G-protein coupled receptor :
They are cell surface receptors which facilitate binding of guanosine triphosphate
to specific protein located on the cytoplasmic surface of plasma membrane,
known as (G protein) which regulate the activity of membrane enzyme adenylyl
cyclase (A.C.) resulting in change in the concentration of the intercellular cAMP
also called second messenger .
Duration :Seconds to minutes

B2-agonist Gs-protein activate AC increase cAmp.

Alpha agonist Gs-protein inhibt AC decrease cAmp.

 Cont. Types of receptor and signal transduction

3- Tyrosine kinase linked receptor :

They are polypeptide receptors,

consisting of an extracellular
ligand-binding domain
( to which insulin or growth hormone bind ).

It is connected to cytoplasmic

enzymatic domain containing
tyrosine kinase enzyme .

Duration :Minutes to hours.

 Cont. Types of receptor and signal transduction

4- receptors that regulate DNA transcription :

 they are stimulate the transcription of
genes in the nucleus leading
to protein synthesis.

Must be lipid soluble.

Like steroid hormones, thyroxine, Vit D .

 Characteristics of receptors

A) Long use of agonist may result in a decrease in number and sensitivity of

receptors (Down regulation)

B) Long use of antagonist like b2 on heart may result in an increase in number and
sensitivity of receptors (Up regulation)

C ) Receptor Desensitization decrease the response with constant number of

the receptors (recognition) . Occurs due to prolonged exposure (use) of the agonist.

D) Tachyphlaxis Rapid tolerance (sudden onset drug tolerance which is not dose
dependent).
E) Signal amplification
• A characteristic of G protein–linked & enzyme-linked receptors is their ability to
amplify signal intensity & duration.
• For example, a single agonist– receptor complex can interact with many G
proteins multiplying the original signal many fold.
• Systems that have signal amplification are said to have spare receptors.

Examples:
1) 95% - 99% of insulin receptors are “spare” this constitutes an immense
functional reserve.
2) 5% to 10% of the total β1- adrenoceptors in human heart are spare.
 Cell Receptor Theory of Clark & Gadduma
Cell

Drug Cell membrane

molecules Cell Receptors
Nucleus

Drug molecules

1 Drug affinity

2 Drug occupancy

3 Drug action

D/R complex

Drug effect
 Body Response According to given Dose

I- Graded response: E max

• The response is
increased
by increasing the dose till ED50

reach the maximal effect at

which most of receptors Potancy

are occupied.
• Importance:
Potency is how much drug
For determination of ED50 , is required to start its
Emax and Potency. effect
 Cont. Body Response According to given Dose
•II- Quantal response:
• The response start to appear only when the dose reach to certain limit or
quantity (it is called all or none response the effect either occurs or not),
responders or non responders e.g anticonvulsant drugs.
• Importance: For determination of LD50 or TD50
Therapeutic index (TI) = LD50 / ED50
 Types of molecules that binds to a receptor

•Agonist: The drug which has affinity, efficacy, rapid dissociation

constant (Kd), and produces an effect.

• Affinity: Tendency of drug to bind with its receptors.

• Efficiency: Ability of drug to produce an effect.

• Efficacy: Ability of drug to produce its maximal effect.

•Antagonist: The drug which blocks cell receptors and

prevent action of the agonist.
It has affinity, NO efficacy and slow Kd.
 Types of Agonists
Total
Partial
(complete)
Agonist
Agonist

Stimulate receptors Stimulate and

and produce block receptor
maximal effect and produce
(Emax) submaximal
i.e. have a high effect
efficacy, high affinity i.e. have a
and high Kd moderate efficacy,
high affinity and
* e.g. Adrenaline on Adrenal
slow Kd
receptor.

* Ach on Muscarinic * e.g. Oxyprenolol on

receptors. β receptors.
 What happen when 2 drugs are given together ?

1-Drug 2-Enhancement of
Antagonism: drug effect:

Decrease or A- Addition.
disappearance of
B- Potentiation.
effect of one of the two
drugs when given C- Synergism.
together.
 Drug Antagonism
Is a condition which occurs when two drugs are
given together and result in a decrease or
disappearance of the effect of one of them.

opposite actions of two drugs on the same

physiological system.
■ Significance: 1- To treat of drug toxicity.
2- To overcome side effects of drugs.
 Types of Drug Antagonism
A. Pharmacological antagonism:
Occurs when an antagonist prevent an agonist from
interacting with its receptors to produce an effect. This type of
antagonism can be either competitive or noncompetitive.

1)Competitive Antagonist:
(a) Competitive antagonists compete with agonists in a reversible
fashion for the same receptor site.
 Cont. Competitive antagonism
(b) When the antagonist is present, the log dose-response curve is
shifted to the right, indicating that a higher concentration of agonist is
necessary to achieve the same response as when the antagonist is
absent.

(c) In the presence of the antagonist, if enough agonist is given, the

Emax can be achieved, indicating that the action of the antagonist
has been overcome.
This results in a parallel shift of the dose-response curve, as shown.

Shift in the log dose-response

curve that occurs when an agonist
is administered in the presence of a
competitive antagonist.
 2) Non- Competitive Antagonism
(a) The non competitive antagonist binds irreversibly to the receptor
site
or to another site that inhibits the response of the agonist.
(b) No matter how much agonist is given, the action of the
antagonist cannot be overcome.
(c) This results in a nonparallel shift of the log dose-response curve
with a lower Emax.

Shift in the log dose-response curve

and lowering of the maximum effect
(Emax) that occurs when an agonist is
given in the presence of a
noncompetitive antagonist
 Cont. Types of Drug Antagonism
B. Physiologic antagonism:
The drugs act independently on two different receptors.

e.g. Adrenaline acting on the sympathetic nervous system

causing vasoconstriction to Blood vessels.

Histamine acting on H receptor that causes vasodilatation of

Blood vessels.
 Cont. Types of Drug Antagonism
C. Chemical antagonism:

Antagonism by neutralization:

e.g. in the neutralization of gastric hyperacidity by

(Antacids) the alkaline salts of sodium and potassium such
as acetates, citrates and bicarbonates.
 Cumulative Effect of Drugs

Definition:
• It occurs when a drug is rapidly absorbed and slowly
excreted and is given repeatedly it may accumulate to
a toxic level or cause death.

Examples of cumulative drugs:

1-Digoxin.
2-Strychnine.
3-Long acting sulpha drugs.
 cont. Cumulative Effect of Drugs

To avoid cumulative effect of drugs:

• Start therapy with initial therapeutic dose followed by

small maintenance dose.

• Give a period of rest during course of therapy.

• Give a diuretic to help excretion of the drug.

• Stop administration of the cumulative drug once toxic

symptoms appear.
 III. Adverse effects of drugs
It is an unpredictable abnormal response to the drug administered
to the body, while side effects are predictable.
Types of Adverse effects:
1) Hypersensitivity (allergic reaction).
The drug may act as antigen and become antigenic.
- It dose not occur on the first exposure and is not dose
dependent.
- It may be manifested as ( urticaria, rash, photosensitivity,
edema, asthma or anaphylactic shock )
- it can be resolved with anti-histamine and steroids.
 cont. III. Adverse effects of drugs
2) Idiosyncrasy (pharmacogenetics)
Abnormal reaction to drug due to genetic or enzyme
defect .
e.g.

- Patients with G-6-PD ( glucose 6 phosphate

dehydrogenase ) which protect RBCs from oxidizing
agents, methemoglobinemia.
 cont. III. Adverse effects of drugs
 Predictable adverse effects:

1- side effect undesirable normal action of the drug.

e.g. atropine as antispasmodic induce dry mouth.

2- secondary effect long use of oral broad spectrum

antibiotics may lead to secondary infection by candida.

3- overdose exaggerated normal action of drug either by

single large dose or accumulation of several small doses.
 cont. III. Adverse effects of drugs
4- supersenstivity exaggerated action to normal dose of a drug
may be due to decrease clearance of drug or upregulation of
receptor .

5- tolerance failure of response to the usual dose of a drug, so

dose is increased.
Types of tolerance
A- congenital
- Racial negroes are resistant to mydriatic effect of ephedrine .
- Species rabbits are resistant to atropine due to atropinase
enzyme in liver and plasma of rabbits which rapidly detoxifies
atropine .
- Individual variations .
 cont. III. Adverse effects of drugs
B- Acquired
Due to repeated administration of certain drugs
E.g. morphine, ethyl alcohol , barbiturates, caffeine,
nitrites…etc.
• After a period of administration, the therapeutic dose
of the drug becomes ineffective.

• Rate of tolerance development varies from drug to

another.

• It is reversible so cessation of the drug will lead to loss

of tolerance .
 cont. III. Adverse effects of drugs
- Causes of acquired tolerance :
• failure of oral absorption .
• Increase biotransformation .
• Increase excretion .
• Down regulation of receptors .

- Special types of tolerance :

Cross tolerance: which develops to one drug by the
administration of another one related, e.g.: tolerance between
alcohol and volatile anesthetics or antibiotics from the same group
Bacterial resistance to chemotherapeutic agents.
 cont. III. Adverse effects of drugs
6- Drug dependency
• Emotional or psychological dependence on drug.
• Addiction (Tissue require the drug to function normally, When
drug stopped, severe withdrawal reaction occur)
• Like morphine, heroin, tobacco smoking and xanthines.

7- Induction of disease
• Aspirin on empty stomach induces ulcers.

8- Carcinogenicity
• - Tobacco smoking induces bronchogenic carcinoma.
 cont. III. Adverse effects of drugs
9- Teratogenicity :
- Drug induce foetal abnormalities especially in first
trimester like aspirin.

10- Cytotoxic effects:

- Drug may produce cell damage.
- E.g.
 8th cranial nerve damage by streptomycin.
 Nephrotoxicity by sulphonamides.
 cont. III. Adverse effects of drugs
11- drug interactions
A) Pharmacokinetic interactions:
■ Absorption:
• Atropine inhibits gastric motility and delay absorption of
drugs taken at the same time.
• Gastric acid pH affects absorption of some drugs, e.g. aspirin.
• Gut content, e.g. milk inhibits absorption of oral tetracycline.
■ Distribution:
e.g. Aspirin displaces oral hypoglycemic from their binding sites
and increase their effect.
 cont. III. Adverse effects of drugs
■ Metabolism:
• Hepatic microsomal enzymes inducers increase drugs
metabolism
• Hepatic microsomal enzymes inhibitors decrease drugs
metabolism thus increase its effect.

■ Excretion:
• Probenecid inhibits renal excretion of penicillin.
• Alkalization of urine increases aspirin excretion.
B) Pharmadynamics interaction:
• Additive effect (Addition or summation): Occur when
2 drugs have the same effect are given together and the
resultant effect equal the sum of both effects when 2 drugs are
given individually i.e

E AB = E A + E B i.e. 1 +1 = 2

• Synergism:
Occur when 2 drugs have the same effect are given together
and the resultant effect is greater than the sum of both effects
when drugs are given individually
E AB > E A + EB i.e. 1+1 >2
 cont. III. Adverse effects of drugs
• Potentiation:
Occurs when one drug has no effect but it increases
the effect of a second active drug i.e.
E AB > E A + E B i.e. O+ 1 >1
Reference
• Karen Whalen; Richard Finkel; Thomas A Panavelil (2015). Lippincott's
illustrated reviews. Pharmacology. 6th edition North American.
Wolters Kluwer. Lippincott Williams & Wilkins