The document discusses drug pharmacodynamics and mechanisms of action. It describes two main types of mechanisms - receptor-mediated and non-receptor mechanisms. Receptor-mediated mechanisms involve drug-receptor interactions that can result in various effects depending on whether the drug is an agonist, antagonist, partial agonist, or inverse agonist. Non-receptor mechanisms involve direct physical or chemical reactions between the drug and other molecules in the body. The document also discusses receptor types, models of drug-receptor interactions, factors that influence drug response, and potential adverse effects of drug interactions and reactions.

1. Pharmacodynamics
Mechanisms of drug action
 It is of two types:
A. Receptor mediated mechanism
Receptors- targets of drug action.
May present either on the cell surface or
inside the cell.
D + R → DR → Biological effect
Where; D=Drug, R=Receptor, DR=Drug Receptor Complex
B. Non-receptor mechanisms
 Simple physical or chemical reaction.
 E.g. Antacids: neutralization reaction.
General Pharmacology 1

2. Types of Receptors
 Regulatory proteins
 For endogenous regulatory ligands – particularly
hormones, growth factors, and neurotransmitters.
 E.g. Insulin receptors-insulin
 Enzymes
 Receptors that are inhibited by binding with a drug.
 E.g. Cyclooxygenase – Aspirin
 Transport proteins: Na+/K+ ATPase- Digoxin
 Structural proteins: Tubulin- colchicine
 Genetic materials: Rifampcin- RNA polymerase
 Ion channels: Na, Ca, K, channel blockers.
General Pharmacology 2

3. Models of D-R interaction…
 Lock & key
 Drug acts as key, receptor as lock, combination
yields response.
 Induced-fit models
 Dynamic & flexible interaction.
General Pharmacology 3

4. General Pharmacology 4
Implications of drug-receptor interaction
 Drugs can potentially alter rate of any function
in the body.
 Drugs cannot impart entirely new functions to
cells.
 Drugs do not create effects, only modify
ongoing ones.
 Drugs can allow for effects outside of normal
physiological range.

5. General Pharmacology 5
Three aspects of drug receptor function
1. Receptors determine the quantitative
relation between drug concentration and
response.
 This is based on receptor’s affinity to bind
and it’s abundance in target cells.
2. Receptors (as complex molecules) function
as regulatory proteins and components of
chemical signaling mechanisms that
provide targets for important drugs.
3. Receptors determine the therapeutic and
toxic effects of drugs in patients.

6. Dose response relationship
General Pharmacology 6
 Dose: amount of a drug required to produce
desired response in an individual.
 Dosage: the amount, frequency and duration
of therapy.
 Potency: measure of how much a drug is
required to elicit a given response. The lower
the dose, the more potent is the drug.
 Efficacy: the intrinsic ability of the drug to
produce an effect at the receptor.
 Maximal efficacy: largest effect that a drug
can produce.

7. Dose response relationship...
Drug response depends on:
 Affinity of drug for receptor.
 Intrinsic activity (degree to which a drug is
able to induce intrinsic effects).
General Pharmacology 7

8. Agonism and Antagonism
 Agonists facilitate
receptor response.
 Antagonists inhibit
receptor response.
(Direct Ant/agonists)
General Pharmacology 8

9. Types of drug-receptor interactions
 Agonist drugs: bind to and activate the receptor
which directly or indirectly brings about the
effect.
 Some agonists inhibit their binding molecules
to terminate the action of endogenous
agonists.
 E.g. slowing the destruction of endogenous
acetylcholine by using acetyl cholinesterase
inhibitors.
 Antagonist drugs: bind to a receptor to prevent
binding of other molecules, but lack intrinsic
activity.
Ge
neraE
l Ph.ag
rma
.coA
logytropine dec
Co
r
me
pile
a
d b
s
y:e
Birha
anu
c
Ge
e
tatylcholine effects.82

10. Types of drug-receptor interactions…
 Partial agonist drugs: acts as agonist or
antagonist depending on the circumstance, have
affinity but have lowered maximal efficacy.
 E.g. Pindolol can act as an antagonist if a “full
agonist” like Isoproterenol is present.
 Inverse agonist: is a ligand which produces an
effect opposite to that of the agonist by
occupying the same receptor.
 E.g. metoprolol in some tissues.
83
General Pharmacology

11.  Full agonist- A drug with high positive efficacy & produce the
system maximal response.
Partial agonist- maximal response to the ligand is below the system
maximal response.
 Antagonists- no efficacy or such a low level of efficacy with no
visible response.
 Inverse agonist- A ligand with negative efficacy can reduce the
basG
e
an
le
r
a
rlP
eh
a
sr
m
pa
oc
o
nl
o
sg
y
e.

12. Graded dose–response relations
 As the concentration of a drug increases, its
pharmacologic effect also gradually increases
until all the receptors are occupied (the
maximum effect).
 It is used to determine affinity, potency,
efficacy and characteristics of antagonists.
General Pharmacology 12

13. Potency
 Is relative strength of response for a given dose.
 Effective concentration (EC50) is the concentration of an
agonist needed to elicit half of the maximum biological
response of the agonist.
 The potency of an agonist is inversely related to
its EC50 value.
 D-R curve shifts left with greater potency.
General Pharmacology 13

14. Efficacy
 Maximum possible effect
relative to other agents.
 Indicated by peak of D-R
curve.
General Pharmacology 14
 Partial agonist =
 Antagonist =
 Inverse agonist =
 Full agonist= 100%
50%
0%
-100%

15. Quantal(cumulative) dose response r/ship:
General Pharmacology 15
 Is between the dose of the drug and the
proportion of a population that responds to it.
 For any individual, the effect either occurs or it
does not (‘all’ or ‘none’).
 Are useful for determining doses to which most
of the population responds; ED50%, TD50%,
LD50%, TI(r/ship b/n dose & toxicity) & inter
subject variability in drug responses.
 They do not predict idiosyncratic reactions and
hypersensitivity.

16. General Pharmacology 16
Therapeutic index
 Median Lethal Dose (LD50): dose which would
be expected to kill one half of a study
population.
 Median Effective Dose (ED50): dose which
produces a desired response in 50% of the
test population.
 Therapeutic Index: gives a rough idea about the
potential effectiveness and safety of the drug in humans.
Therapeutic Index (TI) = LD50/ED50
The smaller the TI, the less safer the drug is.
 Margin of safety=LD1/ED99.

17. Therapeutic Index…
ED50
General Pharmacology 17
LD50

18. Factors modifying the dosage & action of drugs
1. Age
2. Sex
3. Body weight
4. Genetics
5. Drug tolerance
6. Drug intolerance
7. Disease states
General Pharmacology 18

19. Drug- Drug interactions
Consequences of Drug- Drug Interactions
1. Intensification of effects: increased therapeutic
or adverse effects.
Additive Drug Effects (Summation): 1 + 1 = 2.
 Most frequently seen when two drugs possess similar intrinsic
activity.
E.g. sedative-hypnotic type drugs (i.e., barbiturates, alcohol,
benzodiazepines (diazepam, etc.) administered in combination
will produce additive effects resulting in over-sedation.
Synergism - the effect of two drugs in combination is greater
than the sum of the drugs administered alone (1 + 1 > 2).
E.g. Aminoglycosides with penicillins.
Potentiation – one substance alone does not have effect
but when added to another chemical, it becomes
effective. (1 + 0 > 1).
General Pharmacology 19

20. 2. Reduction of effects – inhibit drug effects;
Either beneficial or detrimental.
Antagonism: it occurs when the effect of one drug
is diminished by another drug.(1+1<1).
Types of antagonism;
 Chemical antagonism or inactivation
 Physiological (functional) antagonism
 Pharmacologic or Receptor antagonism
 Pharmacokinetic/Dispositional antagonism
General Pharmacology 20

21. Basic mechanisms of Drug- Drug interactions
 Direct chemical or physical interaction - can occur
with drugs mixed together.
 Pharmacokinetic interaction – can alter all four
processes.
 Absorption – increase or decrease (e.g., PH, laxative,
changes in blood flow).
 Distribution – competition for protein binding or changes in
extra cellular PH.
 Metabolism - induction of drug metabolizing enzymes,
inhibition of metabolizing, and competition of metabolism.
 Excretion - altered renal excretion (e.g. filtration,
reabsorption, and secretion).
 Pharmacodynamic interaction
 Interactions at same receptor – almost always
inhibitory.
 Interactions resulting from actions at separate sites
(if drugs influence same physiologic process).
General Pharmacology 21

22. General Pharmacology 22
Drug- Food interactions
 Impact of Food on Drug Absorption
– Decreasing rate and/or extent of absorption
– Some foods can increase extent of drug
absorption.
 Impact of Food on Drug metabolism
– The grapefruit juice effect (can inhibit
metabolism of certain drugs  increased drug
levels).
 Impact of Food on Drug Toxicity
– MAOIs with tyramine
– Caffeine with theophylline
 Impact of Food on Drug Action
– Vitamin K with warfarin.

23. General Pharmacology 23
Adverse drug reactions (ADRs)
 Any undesired response to a drug.
 Can range in intensity from annoying to life
threatening.
Types of adverse drug reactions
 Side Effects: unavoidable secondary drug effect
produced at therapeutic drugs doses.
E.g. 1. Drowsiness that often accompanies the use of
antihistamines
2. Gastric bleeding that can be produced by low
therapeutic doses of aspirin.
 Toxicities: an adverse drug reaction caused by
excessive levels of drug.
E.g. Coma caused by overdose with morphine.
 Allergic reactions:
– Prior sensitization of the immune system.
– Re- exposure to that drug can bring on an allergic response.
E.g. Penicillin allergy

24. General Pharmacology 24
ADRs...
 Idiosyncratic effects: an unusual drug response
resulting from a genetic predisposition.
 Physical dependence: a state in which the body
has adapted to prolonged drug exposure in such a way
that if drug use is discontinued abstinence syndrome
will result.
 Develop during long-term use of certain drugs (e.g. Opoids,
barbiturates etc)
 Carcinogenic effects: ability of certain
mediations /chemicals to cause cancer.
Although a number of carcinogenic compounds have
been identified, very few of these are employed
therapeutically.
 Teratogenic Effects: drug- induced birth defect.