1) Receptors are specific macromolecular proteins that interact with drugs to produce changes in biological systems. Receptors have drug-binding sites and biologically active sites, and determine quantitative drug effects. Receptors mediate actions of agonists and antagonists. 2) Agonists fully or partially activate receptors to produce responses resembling endogenous ligands. Full agonists have maximal efficacy while partial agonists have submaximal efficacy. Inverse agonists decrease constitutive receptor activity. 3) Some drugs act through non-receptor mediated mechanisms like interfering with ion passage through cell membranes, inhibiting enzymes or transport processes, or directly interacting with molecules outside cells.

1. BY
Prof Dr Samina Karim
1

2.  Pharmacodynamics
 Receptors
 Mechanism of drug action - non receptor
mediated
2

3. “What the drug does to the body”
Pharmacodynamics include mechanism of
drug action , pharmacological actions ,
adverse effects , and clinical uses of drugs
 Mechanism of action
a. Receptor mediated
b. Non receptor mediated
 Effect of drugs – can be local or systemic
 Drug-body interaction results in response,
stimulation or depression, irritation,
replacement, and cytotoxic action.
3

4. 4

5. For a few or minority of drugs
 pharmacodynamics properties are
determined by some physicochemical
properties
 Mechanism does not require highly
specific chemical structure.
5

6. 1--By Acting On Cell Membrane
a) Interference with selective passage
of ions across membrane.
Calcium entry through calcium
channels is blocked by calcium
channel blockers
b) Physicochemical interaction.
General and local anesthetic and
alcohol act on the lipid protein
water constituents of nerve cell
membranes

7. 2-- By acting on metabolic processes
within the cells
a) Enzyme inhibition.
physostigmine inhibits cholinesterase,
allopurinol inhibits xanthine oxidase.
b) Inhibition of transport processes that carry
substances across cells.
blockade of anion transport in renal tubules
by probenecid .
7

8. 2-- By acting on metabolic processes within the cells
c) Incorporation into large molecules.
5 – fluorouracil incorporated into
messenger – RNA in place of uracil
d) Altering metabolic processes unique to
microorganisms, e.g., inhibition of
folic acid synthesis by trimethoprim;
inhibition of synthesis of bacterial
cell wall by penicillin.
8

9. 3-- By Acting outside the cell
a) Direct chemical interaction
antacids NaHco3, chelating agent
deferoxamine
b) Osmosis
osmotic purgative MgSo4,
osmotic diuretic Mannitol
9

10. 10

11. “Receptors- are
specific
macromolecular
proteins in a
biological system
with which drugs
interact to
produce changes
in the function of
system.”
11

12. Concept of receptors
Originated from experimental work of
Ehrlich and Langley during late 19th and
early 20th centuries
Many drugs must bind to a receptor to
produce an effect. Effector may be part of
receptor or may be separate molecule.
Receptors communicate with their effectors
through coupling molecule .
 Drug (D) + receptor- effector ( R) drug
receptor effector complex  effect
 D+R  drug receptor complex 
effector molecule  effect
12

13.  D+R  D.R Complex  activation of
coupling molecule  effector molecule 
effect
 Inhibition of metabolism of endogenous
activator  increased activator action on
an effector molecule  increased effect
Receptors can exist in inactive non-functional
form Ri and can exist in activated form Ra .
Agonists have much higher affinity for Ra ,so
large percentage of the total pool resides in
the Ra –D fraction and a large effect is
produced .
13

14. Drug
Receptor
Protein undergoes
an alteration in
conformation
which produces or
which induces
changes in the
system
14

15. Characteristics of receptors
 Receptors are biologically important molecules
 Receptors must have a drug-binding site and a
biologically active site .
 Receptors largely determine the quantitative
relations b/w dose or concentration of drug and
pharmacological effects.
Receptor’s Affinity for binding a drug determines
the conc . of drug required to form a
significant no. of drug – receptor complexes
and total number of receptors may limit the
maximal effect a drug may produce.
15

16. Characteristics of Receptors
 Responsible for Selectivity of response
mol. size , shape and charge of drug determine
whether and with what affinity it will bind to a
particular receptor and produce response.
 Receptors mediate the action of
pharmacological agonists and antagonists
16

17.  Regulatory proteins – mediate the action of
endogenous chemicals e.g. Hormones,
Neurotransmitter, Autacoids.
 Enzymes – may be inhibited or less
commonly activated e.g. dihydrofolate
reductase acts as a receptor for
methotrexate.
 Transport proteins – e.g. Na+ /K+ ATPase the
membrane receptor for digitalis glycosides .
17

18.  Structural proteins – e.g. tubulin, receptor
for colchicine.
 Orphan receptors – their ligands are
presently unknown they may prove to be
useful targets for future drug development.
18

19. “Binding of drug with a Receptor”
19
“After binding of a drug with a
receptor-- activation of receptor effector
system occurs”
Efficacy
Ability of a drug to produce physiological or
pharmacological response when it interacts
with receptor.

20. Agonist
“Drug which binds to a receptor and
produce a biological response that
resembles the response to endogenous
ligand .”
e.g.
a) Phenylephrine.
b) Salbutamol /albuterol.
c) Adrenaline /epinephrine.
20

21.  Full agonist
 Partial agonist
 Inverse agonist
21

22. Agonist
Agonist has both affinity and efficacy
(maximal intrinsic activity).
“Agonist binds to a receptor and produce
a biological response that resembles the
response to endogenous ligand .”
Agonists cause a shift of almost all of the
receptor pool to the Ra- D pool.
These are also known as full agonist.
Examples—epinephrine , albuterol,
morphine.
22

23. Partial agonists have affinity and
submaximal intrinsic activity, bind to
the same receptors and activate
them in the same way as full
agonists but do not evoke a great
response even with high conc.
 Partial agonist may act either as an
agonist (in the absence of full
agonist ) or as an antagonist ( in the
presence of full agonist ).
23

24. • Have efficacy greater than zero
Less than that of full agonist
• Partial agonists produce concentration
effect curves that resemble those
observed with full agonist in the
presence of antagonist
• Example: Pindolol, Acebutolol -- ISA
24

25. Inverse agonists have a higher affinity
for inactive Ri state than for Ra and
decrease or abolish any constitutive
activity.
Such drugs produce effects that are
opposite of the effects produced by
conventional agonist at that receptor.
25

26. EXAMPLE
GABAa receptor-effector in the nervous system ,
activated by GABA and causes inhibition of
postsynaptic cells producing sedation.
Conventional agonist benzodiazepine also
facilitates this receptor effecter and produces
GABA like inhibition - sedation, muscle relaxation
and acts as anxiolytic.
Substances called ß – carbolines also bind and
activate this receptor, cause anxiety and agitation,
the inverse of sedation . Inverse agonists have been
found for ß receptors, histamine receptors.
26

27. 27
The set of properties that characterize the
effects of drug on the body is called
a) Distribution
b) Permeation
c) Pharmacodynamics
d) Pharmacokinetis
e) Protonation

28. In the absence of other drugs, pindolol causes
an increase in heart rate by activating beta
adrenoceptors. In the prescence of highly
effective beta stimulants, however, pindolol
causes a dose-dependent, reversible
decrease in heart rate. Therefore, pindolol
should be classified as
a)A chemical antagonist
b)An reversible antagonist
c)A partial agonist
d)A physiologic Antagonist
e)A spare receptor
28

29. Which one of the following is a type of
protein receptor
a) Hormones
b) Complex polysaccharides
c) Nucleic acid
d) Penicillin
29

30. 1) a) Define receptor? Discuss characteristics
of receptor.
2) b) Discuss different types of agonists
3) Discuss non-receptor mediated mechanism
of drug action.
30

31. 31