PHARMACODYNAMICS
Mechanism of action
Dr. Irfan Ahmad Khan
Assistant Professor
Deputy Co-ordinator, ADRMC, JNMC
At the end of the talk you should be able
to understand:
• What is Pharmacodynamics?
• What is the Site of Action of the drugs?
• How drugs interacts with receptors?
• How Receptors produces intracellular and
extracellular action?
• In Greek
Pharmacon = Drug Dynamics = Action/Power
It covers all aspects relating to
“What a drug does to the body”
Mechanism of action
Absorption
• Action: How and Where the
effect is produced is called
as Action
• Effect: The type of response
produced by drug
Types of Drug Action
EFFECT (Type of responses):-
1.Stimulation
2.Inhibition/Depressio
n 3.Replacement
4.Irritation 5.Cytotoxic
Physical/ Chemical Methods
• All drugs action are not mediated by receptors.
Some of drugs may act through chemical action
or physical action or other modes.
• Bulk laxatives (ispaghula)—physical mass
• Mannitol, mag. sulfate—osmotic activity
• Antacids—neutralization of gastric HCl
ENZYMES
ION CHANNELS
• Proteins which act as ion selective channels
participate in transmembrane signaling and regulate
intracellular ionic composition
• Sulfonylurea hypoglycaemics inhibit pancreatic ATPsensitive K+ channels.
• Nifedipine blocks L-type of voltage sensitive Ca2+
channel
TRANSPORTERS
•
Substrates are translocated by binding to specific
transporters (carriers)
•
Desipramine and cocaine block neuronal reuptake
of noradrenaline by interacting with NE transporter
(NET)
•
Hemicholinium blocks choline uptake into
cholinergic neurones and depletes ACh.
Receptor Mediated action
• Receptors macromolecules, Mostly proteins
• Present either on cell surface, cytoplasm or in nucleus
• Recognize signal molecule and initiate response to it
• It usually, has no function of its own
D
Actio
n
Extracellular
Environment
Intracellular Environment
Drug(D) +Receptor®
Drug receptor complex
Response
Drug receptor interaction:1. Selectivity:- Degree of complimentary co-relation
between drug and receptor. Ex:- Adrenaline
selectivity for α, ß Receptor
2. Af fin ity:- Ability of drug to get bound to the
receptor.
3. Intrinsic activity (IA) or Ef ficacy:- Ability of drug
to produce a pharmacological response after
making the drug receptor complex.
Drug classification
(on the basis of af finity & efficacy)
Response
No response
• Partial agonist : These drug have full
affinity to receptor but with low intrinsic activity
(IA=0 to 1).
• These are only partly as effective as agonist
Ex: Pentazocine
• Inverse agonist: These have full af fin ity
towards the receptor but intrinsic activity is
zero to -1 i.e., produ ces effect is j u s t
opposite to that of agonist.
• Ex : - ß- C ar b ol i n e i s i n v e rs e agon i s t for
Benzodiazepine receptors.
D
A
Opposit
e action
t
o
Agonist
Typ
e
Affinit
y
Intrinsi
c
Activit
y
Inverse
Agonist
+1
D
D
Partia
l Effe
ct
Competitiv
e Antagon
ist
Agonis
t
+
1
+
1
Ra
Antagonis
t
+
1
0
Ra = Ri
Ri
0 to
+1
Ra > Ri
βAgonist
βAntagonist
βCarboline
Pentazocin
(μ)
0 to -1
Partial
Agonist
+1
Receptor families
Four types of receptors families
1. Ligand-gated ion channels (inotropic
receptors)
2. G-protein coupled receptor (Metabotropic
receptors)
3. Enzymatic receptors (tyrosine kinase)
4. Receptor regulating gene expression
(transcription factors/ Steroid )
Characteristics of receptor
families
Ligand
G-protein
Enzymatic
gated
Nuclear
coupled
Location Membrane
Membrane
Membrane
Intracellular
Effector
Ion Channel
or enzyme
Enzyme
Gene
Coupling Direct
G-protein
Direct
Via DNA
Example
Muscarinic
Insulin
Steroid
hormone
Ion channel
Nicotinic
Varieties of G-protein
G-protein
Receptor for
Signaling pathway/
Effector
AC— cAMP
Gs
ß adrenegic, H2,
Glucagon
Gi
α2 adrenergic, M2,
Opioid
Gq
α1, H1, M1
Phospholipase-C,
IP3’ cytoplasmic Ca2+
Go
M2, D2
Ca2+ channel
inhibition
Adenylyl cyclase activation, Ca2+
channel opening
AC—
cAMP,
Open K+
0
