Pharmacodynamics, Receptors and their types, G protein coupled receptors, Ion channels, Enzyme linked receptors, Intracellular receptors

1. PHARMACODYNAMICS
By
Dr. Faraza Javaid

3. Pharmacon = Drug , Dynamics = Action/Power
“What a drug does to the body”
Pharmacodynamics describes the
actions of a drug on the body.

4. Action
How and Where the effect is produced is called as
Action.
Effect
The type of response producing by drug.

5. Site of Drug Action
1. Extra cellular
2. Intracellular

6. Types of Drug Action
EFFECT (Type of responses):
1.Stimulation
2.Inhibition/Depression
3.Replacement
4.Irritation
5.Cytotoxic

7. Mechanism of Action of Drugs
Drug act either by receptor or by non receptor or by
targeting specific genetic changes.
Majority of drugs acts by (HOW)
Receptor mediated Non receptor mediated

8. Receptor Mediated Action
 Drug produce their effect through interacting
with some chemical compartment of living
organism c/s Receptor.
 Receptors are macromolecules
 Most are proteins
 Present either on the cell surface, cytoplasm or
in the nucleus

9. Receptors
Receptor is a macromolecule in the membrane or
inside the cell that specifically (chemically) bind a
ligand (drug).
Unoccupied receptors does not influence
intracellular processes.
Drug + Receptor Drug receptor complex Response

10. Signal Transduction
Signal transduction (also known as cell signaling) is the
transmission of molecular signals from a cell's
exterior to its interior.
Signals received by cells must be transmitted
effectively into the cell to ensure an appropriate
response.
Drugs act as signals, and receptors act as signal
detectors.
“Second messenger” or effector molecules are part of the
cascade of events that translates agonist binding into a
cellular response.

11. Receptor Functions
1. Recognization of specific ligand molecule
(Ligand binding domain)
2. Transduction of signal into response (Effector
domain)
Ligand binding
domain
Transduction of
signal into response

12. Drug Receptor Interaction
1. Selectivity:- Degree of complimentary co relation
between drug and receptor.
Ex:- Adrenaline Selectivity for α, ß Receptor
2. Affinity:- Ability of drug to get bound to the
receptor.
3. Intrinsic activity (IA) or Efficacy:- Ability of drug
to produce a pharmacological response after
making the drug receptor complex.

13. Drug Classification
(on the basis of affinity & efficacy)

14. Response No response

15. Receptor Families
Four types of receptors families:
1. Ligand-gated ion channels
2. G-protein coupled receptor
3. Enzyme Linked receptors
4. Intracellular/ Receptor regulating gene expression
(transcription factors/ Steroid )

16. Ligand-Gated Ion Channels
Ion channels are pore-forming membrane proteins whose
function is establishing a resting membrane potential,
shaping action potentials and other electrical signals by
gating the flow of ions across the cell membrane,
controlling the flow of ions across membranes, and
regulating cell volume.
Functions:
Neurotransmission
Muscle contraction

20. G-Protein Coupled Receptor
G proteins, also known as guanine nucleotide-
binding proteins, involved in transmitting signals
and function as molecular switches.
Produce effects by:
 Adenylyl Cyclase
 Phospholipase C

21. There are many kinds of
G proteins (for example,
Gs, Gi, and Gq), but all
types are composed of
three protein subunits.
The α subunit binds
guanosine triphosphate
(GTP), and the β and γ
subunits anchor the G
protein in the cell
membrane.

23. GTP
GDP
 GDP
GTP

ATP
cAMP
Cell response
AT
Protein
kinase
ADP
P
Inactive
protein
Active
protein
hormone
Adenylate cyclase
Signaling System
AC
RS
Inhibitor
Ri



25. Varieties of G-protein
G-protein Receptor for Signaling pathway/
Effector
Gs ß adrenergic,
5HT,
AC— cAMP
Gi α2 adrenergic, Ach, AC— cAMP,
Open K+
Gq Ach Phospholipase-C, IP3
Go Neurotransmitters
in brain
Not yet clear

26. Enzyme Linked Receptors
A group of transmembrane proteins that contain
either intrinsic enzyme activity on their
intracellular domain or associate directly with an
intracellular enzyme.
1. Receptor tyrosine kinases
2. Tyrosine-kinase-associated receptors
3. Receptor serine/threonine kinases
4. Histidine-kinase-associated receptors
5. Receptor tyrosine phosphatases
6. Receptor guanylyl cyclase

27. Basic Receptor Structure
1. Ligand-binding domain
Extracellular to allow easy access for ligands.
Bind to same receptor to produce particular
cellular responses.
2. Transmembrane domain
Contains a series of hydrophobic amino acids.

28. 3. Cytosolic
"active" enzyme
domain
The intracellular
domain of receptor
itself is an enzyme
or interacts directly
with an enzyme.

30. Intracellular/ Receptor
The fourth family of receptors differs considerably from
the other three in that the receptor is entirely intracellular,
and, therefore, the ligand (for example, steroid hormones)
must have sufficient lipid solubility to diffuse into the cell to
interact with the receptor.
The primary targets of activated intracellular receptors are
transcription factors in the cell nucleus that regulate gene
expression. The activation or inactivation of transcription
factors alters the transcription of DNA into RNA and
subsequently translation of RNA into proteins.
Other targets of intracellular ligands are structural
proteins, enzymes, RNA, and ribosomes.

32. Characteristics of Receptor Families
Ligand
gated
G-protein
coupled
Enzymatic Nuclear
Location Membrane Membrane Membrane Intracellular
Effector Ion channel Ion Channel
or enzyme
Enzyme Gene
coupling Direct G-protein Direct Via DNA
Example Nicotinic Muscarinic Insulin Steroid ,
hormone

34. Characteristics of Signal Transduction
Signal transduction has two important features:
1)The ability to amplify small signals and
2)Mechanisms to protect the cell from excessive
stimulation
 Desensitization or down regulation of receptor
 Tachyphylaxis

35. THANK YOU