pharmacodynamics - mechanism of drug action and their receptor that is part of general pharmacology.

1. Pharmacodynamics -
Mechanism of drug action and their
Receptor
Presented by-
ARCHITA SRIVASTAVA
M.PHARM 1ST YEAR
Department of pharmacology

2. CONTENTS
 Principle of drug action
 Mechanism of drug action
 Receptor
Drug receptor interaction
Types of receptors
Working of receptors
Reference

3.  Drug do not impart new function to any system , organ
or cell , they only alter the pace of ongoing activity.
 Types of drug action -
• Stimulation
• Depression
• Irritation
• Replacement
• Cytotoxic action
Principles of Drug Action

4. Mechanism of Drug Action
 Receptor mediate  Non receptor mediate
 GPCR  By physical action
 Ligand gated ion channel  By chemical action
 Enzymatic receptor  By ion channel
 Nucleus receptor  By enzymes
 By transporters

5. Mechanism of Drug Action- Enzymes

6. Several substrates are translocated across membranes
by binding to specific transporters (carriers) which either facilitate
diffusion in the direction of the concentration gradient or pump
the metabolite/ion against the concentration gradient using
metabolic energy
Mechanism of Drug Action- Transporters

7. Receptor are macromolecules present either on the cell surface ,
cytoplasm or in the nucleus with which the drug binds and
interact to produce cellular response.
 Receptor are protein in nature.
Mechanism of Drug Action-Receptors

8. Agonist- An agent which activates a receptor to
produce an effect similar to that of the physiological
signal molecule
Inverse agonist- An agent which activates a receptor
to produce an effect in the opposite direction to that of
the agonist.
Antagonist- An agent which prevents the action of
an agonist on a receptor or the subsequent response, but
does not have any effect of its own.
Partial agonist- An agent which activates a receptor
to produce submaximal effect but antagonizes the
action of a full agonist.
Mechanism of Drug Action- Drug –Receptor
Interaction

9. Agonist- have both affinity and maximal intrinsic
activity (IA = 1), e.g. adrenaline.
Inverse agonist- have affinity but intrinsic activity with
a minus sign (IA between 0 and -1), e.g. DMCM (on
benzodiazepine receptor).
Antagonist- have affinity but no intrinsic activity
(IA = 0), e.g. propranolol.
Partial agonist- have affinity and submaximal intrinsic
activity (IA between 0 and 1), e.g. pentazocine (on µ
opioid receptor).
Mechanism of Drug Action- Drug –Receptor
Interaction

10. Occupation of a receptor by a drug molecule may or may not result in
activation of the receptor. By activation, we mean that the receptor is affected
by the bound molecule in such a way as to alter the receptor’s behaviour
towards the cell and elicit a tissue response. The molecular mechanisms
associated with receptor activation are
Mechanism of Drug Action- Drug-Receptor
Interaction

11. Mechanism of Drug Action-
1.G Protein Coupled Receptor
These are sometimes called metabotropic or seven-trans membrane domain
(7-TDM) receptors
 Structures comprise seven membrane-spanning α-helices, often linked as
dimeric structures
 The third intracellular loop interacts with the G protein
 The G protein is a membrane protein comprising three subunits (α, β, γ),
the α subunit possessing GTPase activity
 When the trimer binds to an agonist-occupied receptor, the α subunit binds
GTP, dissociates and is then free to activate an effector (e.g. a membrane
enzyme)

12. The α- subunits into four families:
Gs
Adenyl cyclase
activation
Increased
cAMP
Gi
Adenyl cyclase
inhibition
Decreased
cAMP
Gq
Phosholipase
C
Increased IP
&DAG
Go
Calcium
channel
inhibition

13. Mechanism of Drug Action-
Cytoplasmic Secondary messengers
Binding of an agonist to a receptor provides the first
message in receptor signal transduction to effectors to
affect cell physiology. The first messenger promotes the
cellular production or mobilization of a second
messenger, which initiates cellular signaling through a
specific biochemical pathway.
Cyclic AMP
Cyclic GMP
Ca2+
inositol Phosphate
Diacyl Glycerol
NO

14. Mechanism of Drug Action- GPCR
I .Adenyl cyclase cAMP pathway

15. MECHANISM OF ACTION – GPCR
II. Phospholypase C – IP3-DAG Pathway

16. MECHANISM OF ACTION – GPCR
III. CHANNEL REGULATION
The activated G- protein [Gs, Gi, Go] can also open or
inhibit ionic channel specific for Ca⁺⁺ and K⁺, without the
intervention of any second messenger like cAMP or IP3
and bring about hyperpolarization/depolarization
/changes in intracellular Ca⁺⁺ ion.
Direct channel regulation is mostly the function of the βγ
dimer of the dissociated G- protein

17. Mechanism of Drug Action-
2.Receptor with Ligand gated ion channel
• These are sometimes called ionotropic
receptors
• They are involved mainly in fast synaptic
transmission
• There are several structural families, the
commonest being heteromeric assemblies
of four or five subunits, with
transmembrane helices arranged around a
central aqueous channel
• Ligand binding and channel opening
occur on a millisecond timescale
• Examples include the nicotinic
acetylcholine, GABA type A (GABAA),
glutamate (NMDA) and ATP (P2X)
receptors

18. Mechanism of Drug Action-
3.Enzyme linked receptors
A) Intrinsic tyrosine protein kinase receptor
B) JAK- STAT Kinase binding receptor

19. Mechanism of Drug Action-
4.Receptors regulating gene expression

20. -

21. REFERANCE -
1. Tripathi K.D, ‘ Essential of Medicinal Pharmacology’’ ,
Jaypee brothers medical publishers , 2015 , seventh
edition , Page no 47-56
2. Rang & Dale’s ‘PHARMACOLOGY’ eighth edition
3. Shanbhag T.V ,etal , “Pharmacology – preparation
manual ” , Reed Elsevier India privet limited, 2014, 2nd
edition no 26-28