‫بسم هللا الرحمن الرحيم‬

‫‪Pharmacodynamics‬‬
 Pharmacodynamics
 Pharmacodynamics: the study of effects of
chemicals and drugs on living system and the
study of mechanisms of these effects.
 This describes the action of the drug on the
body, including receptor interactions, dose
response phenomena, and mechanisms of
therapeutic and toxic action.
 (it is about what the drug does to the body)

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 Binding of drug molecules to cells
 Most drugs produce their effects by binding
to protein molecules (enzymes e.g.
acetylcholinesterase, carrier molecules e.g.
choline carrier, ion channels e.g. voltage
sensitive K+, Ca++, Na+ channels and
receptors e.g. α & β adrenoceptors).

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 Binding of drug molecules to cells
 There is some exceptions such as:
1. Osmotic diuretics.
2. Neutralizing antacids.
3. Bisphosphonates (e.g: etidronate) used to
treat osteoporosis bind to calcium salts in the
bone matrix, rendering it toxic to osteoclasts.

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 Protein targets for drug binding
1. Enzymes e.g.
Acetylcholinesterase ,
xanthine oxidase,
carbonic anhydrase, dopa
decarboxylase, MAO and
COMT.
2. Carrier molecules
(transporters) e.g.
choline carrier (blocked
by hemicholinium), SSR
5 , NA uptake.
 Protein targets for drug binding
3. Ion channels: (pore-forming
proteins that help establish
and control the small voltage
gradient across the plasma
membrane of all living cells)
e.g. voltage sensitive K+,
Ca++, Na+ channels.
4. Receptors e.g. α & β
adrenoceptors, acetylcholine
muscarinic and nicotinic
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receptors.
 Types (families) of receptors
Type 1: Ion channel linked receptors:
• They are membrane (transmembrane)
receptors e.g. acetylcholine nicotinic
receptor, GABAA and glutamate receptors.
• They are coupled directly to ion channel,
• They are receptors on which fast
neurotransmitters act (response within
milliseconds).

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 Types of receptors
Type 2: G-protein coupled receptors:
 They are membrane (transmembrane)
receptors which are coupled to intracellular
effectors system via a G- protein e.g. Ach
muscarinic receptors, adrenergic receptors
(both α and β) and receptors of many
hormones.
 (Response occur within seconds).

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 Types of receptors
Type 3: Kinase linked receptors:
 They are membrane (transmembrane)
receptors which incorporate an intracellular
protein Kinase domain (usually tyrosine
Kinase) within their structure e.g. receptors
for insulin, growth hormone and various
cytokines.
 (Response occur within hours).

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 Types of receptors
Type 4: Receptors that regulate gene
transcription:
 known as nuclear receptors they are
cytosolic or intranuclear proteins. Ligand must
be highly lipophilic; targets are usually
transcription factors.
 They include receptors for steroids hormones,
thyroid hormones, and other agents such as
retinoic acid and Vitamin D.
 (Response occur within hours).
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 1) Lipophilic ligand (e.g.
testosterone) diffuses through 1
the plasma membrane.

2) Testosterone binds to its

3) Hormone-receptor complex 3
enters the nucleus binds to the
target transcription factor on
DNA. 4
4) Target mRNA is
transcribed, and target protein
is synthesized (biological
effect).
 Drugs & receptors
 Drug acting on a receptor may be agonist (full/
partial agonis) or antagonist.
 Agonist: is the drug which it when bind to its
receptor it initiate changes in the cell function
producing effects of various types.
 Antagonist: is a drug that binds to the receptor
without initiating such changes.

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 Drugs & receptors
 Agonist potency depend on affinity
(tendency to bind to receptor) and efficacy
(ability once bound to initiate changes that
lead to effect).
 Full agonist produces maximal effect, so it
has high efficacy.
 Partial agonist produces sub maximal
effect, so it has intermediate efficacy.
 Antagonist has affinity but zero efficacy.
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Potency & efficacy
 Drugs & receptors
 Occupation is governed by affinity while
activation is governed by efficacy.

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 Drug Antagonism
 Drug antagonism can be defined as a decrease
or complete abolition of the effect of one drug
in the presence of another.
 Types of drug antagonism:
1. Chemical (pharmaceutical) antagonism:
 Occur when two substances combine in
solution, so that the effect of the active drug is
lost e.g. dimercaprol (chelating agent) and lead.

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 Drug Antagonism
2. Pharmacokinetic antagonism:
 The antagonist effectively reduces the
concentration of the active drug at its site of
action e.g. warfarin and phenobarbitone (the
last is enzyme inducer that increase the
metabolism of the other).

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 Drug Antagonism
3. Antagonism by receptor block
(Competitive antagonism):
i. Reversible Competitive
antagonism:
e.g. atropine + Ach, it is
surmountable antagonism
characterize by parallel shift of the
log dose – response curve; there is
no reduction on the maximal
response.
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 Drug Antagonism
ii. Irreversible competitive
antagonism:
 The antagonist dissociate very slowly, or
not at all from the receptors (occur with
drugs that have reactive group which
form covalent bond with receptors) e.g.
(noradrenaline with phenoxybenzamine
) (5HT & methysergide), this type of
drug antagonism is characterize by non
surmountable, reduced maximal
response and non parallel shift in the
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log-dose response curve.
 Drug Antagonism
4. Noncompetitive antagonism:
 The antagonist blocks the chain of events (at
some point) that leads to the production of a
response by the agonist. e.g. Verapamil
block Ca++ influx so it decrease the
contraction induced by noradrenaline in
smooth muscles, so it decrease its slope and
maximal response.

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 Drug Antagonism
5. Physiological antagonism:
 Interaction of two drugs whose opposing
action in the body tend to cancel each other
e.g. NA and Ach on the vascular smooth
muscles, NA and histamine on bronchioles ,
histamine and omeprazole on the gastric
parietal cells.

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 Pharmacology – terminology
 Desensitization and tachyphylaxis:
 Gradual decrease of the response of a drug
when given continuously or repeatedly that
develops in few minutes.
 Tolerance: is more gradual decrease in
response of a drug when given continuously or
repeatedly (days or weeks).
 Refractoriness: loss of therapeutic efficacy.
 Resistance: loss of effectiveness of
25 antimicrobial.
 Pharmacology – terminology
 Idiosyncratic reaction: is abnormal and usually
harmful drug effect that occurs in small
proportion of individuals e.g. chloramphenicol
causes aplastic anemia in approximately 1 in
50,000 patients.
 Teratogenesis: production of developmental
malformations of the fetus e.g. the absence of
limbs after thalidomide, Teratogenesis usually
occurs during the first trimester.
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 Thalidomide phocomelia

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 Pharmacology – terminology
 Therapeutic index: the therapeutic index
also known as therapeutic ratio or range is
comparison of the amount of a therapeutic
agent that causes the therapeutic effect to the
amount that causes toxic effects.
 A commonly used measure of therapeutic
index is the toxic dose of a drug for 50% of
the population (TD50) divided by the
minimum effective dose for 50 % of the
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population (ED50).
 Therapeutic index
 Therapeutic index
= TD50
ED50
 Drugs with lower
therapeutic index such as
digoxin, dimercaprol,
theophylline, lithium
and warfarin require
drug monitoring.
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Therapeutic index (TI) (Small vs. large)
With smaller TI, you need to consider benefits over risks of
giving a drug. Larger TI are safer for use.

Small therapeutic Large therapeutic Index

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 Study Questions
 The following pair of drugs is an example of
noncompetitive antagonism:
A. Dimercaprol – lead.
B. Phenobarbitone – warfarin
C. Atropine – acetylcholine
D. Phenoxybenzamine – noradrenaline
E. Noradrenaline – verapamil

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