The document discusses pharmacodynamics and drug targets. It defines pharmacodynamics as the study of the biochemical, cellular, and physiological effects of drugs and their mechanisms of action. It outlines the main drug targets as ion channels, transporters, enzymes, and receptors. Receptors are described as the macromolecules that recognize signal molecules/drugs and initiate a response, and are further classified based on their intracellular signaling molecules.

1. Pharmacodynamics
Dr. Pravin Prasad
MBBS, MD Clinical Pharmacology
Assistant Professor, Department of Clinical Pharmacology
Maharajgunj Medical Campus, TU
14 February 2020 (2 Falgun 2076), Friday

2. By the end of this class, BSc MLT IInd year
students will be able to:
• Explain the term pharmacodynamics and its components
• List the common drug targets involved in drug action with examples
• Appraise the different types of:
• Drug enzyme interaction
• Drug receptor interaction

3. Introduction

4. Introduction
• Pharmacodynamics is the study of the biochemical cellular
and physiological effects of drugs and their mechanisms of
action
• Pharmacodynamics:
• What drugs do?
• Effects
• How drugs do it?
• Mechanism

5. Principles of Drug action
• Stimulation
• Increased secretion of saliva due to acetylcholine
• Depression
• Relaxation of uterine muscle by salbutamol
• Irritation
• Local injection of alcohol in refractory neuralgia
• Replacement
• Insulin in diabetes milletus
• Cytotoxic action
• Antimicrobials

6. Mechanism of Drug action
• By virtue of physical property
• Sunscreen
• By virtue of chemical property
• Antacids
• By interacting with protein molecules
• Colchicine
• By interacting with nucleic acids
• Sulfonamides

7. • By interacting with macromolecular
functional proteins:
• Ion channels
• Transporters (Carriers)
• Enzymes
• Receptors
• Drug targets
• Cellular macromolecule or
macromolecular complex with which the
drug interacts to elicit a cellular or
systemic response.
Mechanism of Action of Drugs
RICE

8. Drug Targets- Ion channels

9. Drug Targets- Ion channels
• Ion channels-
• Modify the intracellular ionic composition of cells
• Drugs can be used to modify their conductance
Drug Ion channel Use
Quinidine
Myocardial Na+
channels
Arrhythmia
Amiodarone Myocardial K+ channels Arrhythmia
Ethosuximide T type Ca2+ channels Epilepsy

10. Drug Targets- Transporters (Carriers)

11. Drug Targets- Transporters
Carrier Transports Blockers
Norepinephrine
transporters
Noradrenaline
(Norepinephrine)
Desipramine,
Cocaine
Gamma butyric
acid transporter
(GAT1)
GABA Tiagabine
Na+ - K+ - 2Cl- co-
transporter
Na+, K+, Cl- Furosemide
Serotonin
Transporter
Serotonin Fluoxetine

12. Drug Targets- Enzymes
• Enzymes:
• Optimises the rate of chemical reaction in our body
• Can be stimulated or inhibited using drugs
• Increase in activity can also occur by enzyme induction
• Enzyme stimulation:
• Thiamine, Pyridoxine: increase decarboxylase activity
• Metabolism of formaldehyde, formic acid enhanced
• Enzyme inhibition:
• Nonselective inhibition: Heavy metal salts, strong acids and alkalis
• Selective inhibition
• Competitive (equilibrium, non-equilibrium type)
• Non-competitive

13. Drug Targets- Receptors
• Receptors:
• Are the macromolecule or binding site located on the surface or inside
the effector cell
• that serves to recognise the signal molecule/drug, and
• initiate a response to it,
• but itself has no other function
• Has two sites
• Ligand binding domain
• Recognition of physiological molecules/ drugs
• Effector domain
• Undergoes functional conformational changes

14. Drug Targets- Receptors
Site 1
Site 2

15. Drug Targets- Receptors
• Types (Based on intracellular signalling molecules)
• G-protein Coupled receptors
• α, β receptors, muscarinic receptors
• Ion channel receptors
• nicotinic ACh receptors, GABAA receptors
• Transmembrane-enzyme linked receptors
• insulin, epidermal growth factors, transforming growth factors
• Transmembrane JAK-STAT binding receptors
• cytokines, growth factors, prolactin
• Intracellular receptors (cytoplasmic/nuclear)
• glucocorticoids, androgens, thyroxine, vitamin D

16. Drug Targets- Receptors
β
Gα
Gγ
cAMP
Phospholipase C Ca2+ channels
K+, Ca2+ channels

17. Drug Targets- Receptors
Agonist
binding Site
α
Na+, K+, Ca2+, Cl-

18. Drug Targets- Receptors
Agonist
binding site
Intracellular
subunit having
enzymatic activity
t

19. Drug Targets- Receptors
Ligand binding
domain
Effector
domain

20. Conclusion
• Pharmacodynamics:
• What drug does, How it does and modification of drug action by another drug
• Five principles of drug action
• Drug Targets: mainly proteins (RICE)
• Other drug targets do exists