1. PHARMACODYNAMICPHARMACODYNAMIC
S (I)S (I)

2. AIMS AND OBJECTIVES
Pharmacodynamics can be defined as the
study of the pharmacological effects of drugs
and their mechanism of action.
The objectives of the analysis of drug action
are to understand the interactions between
drug and target cells, and to characterize the
full sequence and scope of action of each
drug.

3. Such a complete analysis provides the
basis for both the rational therapeutic
use of a drug, and the development of
new and better therapeutic agents.

4. RECEPTORS
Specialized target macromolecules
present on the CELL SURFACE or
INTRACELLULARLY.

5. They are the specific molecules in a
biological system with which drugs
interact to produce changes in the
function of the system.
RECEPTORS

6. Among the most important drug
receptors are the cellular proteins
whose normal function is to act as
receptors for endogenous regulatory
ligands i.e. Hormones,
Neurotransmitters.
RECEPTORS

7. Two functional domains with in the receptors:
1. Ligand binding domain
2. Effector domain
Drug + Receptor Drug Receptor
Complex
↓
Biological Effect
RECEPTORS

9. 1. LIGAND GATED ION
CHANNELS
The ligand gated trans membrane ion
channels that are responsible for the
regulation of flow of ions across cell
membrane.
Changes in membrane potential or ion
concentration with-in cell → Effects

10. EXAMPLES:
NICOTONIC receptors
GABA receptors
1. LIGAND GATED ION
CHANNELS

15. 2. G-PROTEIN COUPLED
RECEPTORS
Binding of the ligand to extra cellular
surface of the trans membrane receptor
activates Gs protein.
The α sub unit of Gs protein dissociates
and activates ADENYLYL CYCLASE.

16. This results in the production of
cAMP, the second messenger, that
regulates protein phosphorylation
and produces biological activity.
2. G-PROTEIN COUPLED
RECEPTORS

23. 3. ENZYME LINKED
RECEPTORS
 The receptor has two hetrodimers each
containing an α subunit and a ß
subunit.
 α subunit is extra cellular and
constitutes the recognition site.
 ß subunit spans the membrane and
contains a Tysosine kinase.

24.  When insulin binds to the α subunit,
Tyrosine Kinase activity in the ß subunit
is stimulated.
 This causes phosphorylation (activation)
of IRS.
 This phosphorylation triggers different
actions of insulin.
IRS: Insulin receptor substrate (1-6)
3. ENZYME LINKED
RECEPTORS

25. Though α ß dimeric form is capable of
binding insulin, it has lower affinity than
α α ß ß tetrameric form.
3. ENZYME LINKED
RECEPTORS

28. 4. INTRA CELLULAR
RECEPTOR
The receptor is entirely intra cellular.
The ligand (lipid soluble) crosses the
cell membrane and combines with the
receptor.

29. The activated receptor then enters the
nucleus where it binds to specific DNA
sequences → Effects.
The response is obtained after about 30
minutes and the duration of the response
(hours to days) is much greater than that
of other receptor families.
4. INTRA CELLULAR
RECEPTOR

30. DRUGS WHICH ACT
INDEPENDETLY OF
RECEPTORS
• ANTACIDS
• CHELATING AGENTS
• OSMOTICALLY ACTIVE DRUGS
Diuretics (Mannitol)
Cathartics (Methyl Cellulose)
• VOLATILE GENERAL ANAESTHETICS

31. OTHER CLASSES OF
PROTEINS THAT HAVE BEEN
CLEARLY IDENTIFIED AS
RECEPTORS
1. ENZYMES
Drugs inhibit the enzymes and
produce effects.
Dihydrofolate reductase is the
receptor for METHOTREXATE

32. 2. TRANSPORT PROTEINS
Na+
/ K+
ATPase
The membrane receptor for
cardioactive Digitalis Glycosides.
OTHER CLASSES OF
PROTEINS THAT HAVE BEEN
CLEARLY IDENTIFIED AS
RECEPTORS

33. 3. STRUCTURAL PROTEINS
Tubulin: The receptor for
Cholchicine, a drug used in the
treatment of GOUT.
OTHER CLASSES OF
PROTEINS THAT HAVE BEEN
CLEARLY IDENTIFIED AS
RECEPTORS

34. AGONIST
DRUGS RECEPTORS
Phenylephrine
Histamine
Acetylcholine
Morphine
α1
H1, H2
M, N
Opioid
A drug which activates the receptors and
elicits maximum response

35. ANTAGONIST
A drug which occupies the receptors, but
instead of activation the receptors are
blocked
DRUGS RECEPTORS
Atropine
Prazosin
Dimetane
Ranitidine
Naloxone
M
α1
H1
H2
OPIOID
Agonists as drugs; Antagonists as drugs

36. PARTIAL AGONIST
A partial agonist has EFFICACY greater than
zero, but less than the full agonist.
Partial agonist: Elicits sub maximal response
Full agonist: Elicits maximal response

37. The tendency of a drug to bind to the
receptors is governed by its AFFINITY, but
the tendency for it to activate the receptors,
after binding with the receptors, is denoted
by its EFFICACY.
PARTIAL AGONIST

38.  A partial agonist will produce sub maximal
response even if 100% of the receptors are
occupied.
 A partial agonist may act as an antagonist
of the full agonist.
PARTIAL AGONIST

40. Example:
The beta blockers: Pindolol, Acebutolol
ß1 andß2 receptors are partially activated, but
are unable to respond to the agonist
Epinephrine.
PARTIAL AGONIST

44. QUESTIONS

45. 1. Binding of GABA to its receptors
opens channels for: -
a) Cl-
b) Na+
c) K+
d) Ca+2
e) H+

46. 2. Binding of Acetylcholine to its
receptors opens channels for: -
a) Cl-
b) Na+
c) K+
d) Ca+2
e) H+

47. 3. A drug which produces its effects
by the stimulation of specific
receptors: -
a) Antacid
b) Mannitol
c) Methyl cellulose
d) Morphine
e) A chelating agent

48. 4. A drug which produces its effects
(antagonism) by the blockade of
specific receptors: -
a) Phenylephrine
b) Histamine
c) Atropine
d) Mannitol
e) Acetylcholine