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1. Pharmacodynamics-I
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Lecturer, Lumbini Medical College & TH
11 December, 2018 (25 Mangsir, 2075),
Tuesday

2. By the end of the class, MBBS
Ist 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. Components of
Pharmacodynamics

6. Principles of Drug action
Stimulation:
Selective enhancement of the level of
activity of specialized cells
Acetylcholine on salivary glands
• Increases secretion of saliva

7. Principles of Drug action
Depression:
Selective diminution of the level of activity of
specialized cells
Salbutamol on uterine muscles
• Contraction of uterus decreased

8. Principles of Drug action
Irritation:
Non-selective, often noxious effect on less
specialized cells
• Capsaicin in herpetic neuralgia
Strong irritation  inflammation, necrosis,
morphological damage
• Local alcohol injection in refractory
neuralgia

9. Principles of Drug action
Replacement:
Use of natural metabolites, hormones, or
their congeners in deficiency states
• Iron supplementation in Iron deficiency
anaemia
• Insulin in Diabetes mellitus

10. Principles of Drug action
Cytotoxic Action:
Selective cytotoxic action on invading
microbes
• Penicillin, cephalosporins
Selective cytotoxic action on cancer cells
• Methotrexate, Cisplatin

11. Mechanism of Action of Drugs
By virtue of physical property:
Isaphgula Laxatives
Dimethicone Ulcer dressing
Para-amino benzoic acid Sunscreen
Activated charcoal Drug overdose
131I radioisotopes Hyperthyroidism

12. Mechanism of Action of Drugs
By virtue of chemical property:
Antacids Hyper-acidity
Potassium permanganate Antibacterial
Chelating agents Heavy metal
poisoning
Cholestyramine
Hypercholesterolemi
a

13. Mechanism of Action of Drugs
By interacting with protein molecules:
Colchicine
Vinca alkaloids
Taxanes
By interacting with nucleic acids:
Alkylating agents
Sulfonamides

14. 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
RIC
E

15. Drug Targets- Ion channels

16. Drug Targets- Ion channels
Ion channels-
Modify the intracellular ionic composition of
cells
Drugs can be used to modify their
conductance
Can be:
Ligand gated
G-protein gated
Receptors

17. Drug Targets- Ion channels
Drug Ion channel Use
Quinidine
Myocardial Na+
channels
Arrhythmia
Amiodarone
Myocardial K+
channels
Arrhythmia
Sulfonylurea
s
Pancreatic K+
channels
Insulin
Phenytoin
Neuronal Na+
channels
Epilepsy

18. Drug Targets- Transporters
(Carriers)

19. 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

20. 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

21. Drug Targets- Enzymes
Enzyme stimulation:
Thiamine, Pyridoxine: increase decarboxylase
activity
• Directly stimulated
• Metabolism of formaldehyde, formic acid
enhanced
Adrenaline: increases hepatic glycogen
phosphorylase
• Stimulated through beta receptors
• Increased glycogen breakdown

22. Drug Targets- Enzymes
Enzyme inhibition:
Nonselective inhibition
• Denature proteins
• Heavy metal salts, strong acids and alkalis
Selective inhibition
• Competitive (equilibrium, non-equilibrium
type)
• Non-competitive

23. 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

24. Drug Targets- Receptors
Has two sites
Ligand binding domain
• Recognition of physiological molecules/
drugs
Effector domain
• Undergoes functional conformational
changes

25. Drug Targets- Receptors
Site 1
Site
2

26. Drug Targets- Receptors
Types (Based on intracellular signalling
molecules)
G-protein Coupled receptors
Ion channel receptors
Transmembrane-enzyme linked receptors
Transmembrane JAK-STAT binding
receptors
Intracellular receptors (cytoplasmic/nuclear)

27. Drug Targets- Receptors
G-protein coupled receptors (GPCRs)
Examples: α, β receptors, muscarinic
receptors
Consists of 7 transmembrane helices
Linked to various effectors
Action seen in seconds
Coupled to G-protein ( α, β and γ)

28. Drug Targets- Receptors
G-protein coupled receptors (GPCRs)
Coupled to different transducer mechanisms
• Gs  cAMP, Gi  cAMP
• Gq  Phospholipase C, Go  Ca2+ channel
β and γ subunits:
• As chaperone
• Receptor operated K+ channels
• Voltage gated Ca2+ channels
• GPCR desensitization

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

30. Drug Targets- Receptors
Ion channel receptors
Examples: nicotinic ACh receptors, GABAA
receptors
Two types:
• G-protein gated
• Ligand gated
Encloses ion selective channels within their
molecules

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

32. Drug Targets- Receptors
Transmembrane enzyme-linked receptors
Examples: insulin, epidermal growth factors,
transforming growth factors
Extracellular and intracellular subunits
connected with single transmembrane helix
Intracellular subunit has enzymatic activity
• Tyrosine, serine/threonine
Response seen in minutes to hours

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

34. Drug Targets- Receptors
Transmembrane JAK-STAT binding receptors
Examples: cytokines, growth factors,
prolactin
Extracellular and intracellular subunits
connected with single transmembrane helix
Intracellular subunit has no enzymatic
activity
• On activation, binds to cytosolic protein
Janus Kinase (has enzymatic activity)

35. Drug Targets- Receptors
Agonist
binding site
Intracellular
subunit with NO
enzymatic
activity
t

36. Drug Targets- Receptors
Intracellular receptors
Examples: glucocorticoids, androgens,
thyroxine, vitamin D
Can be present in cytoplasm or within
nucleus
Ligand binding domain- carboxy terminus
Effector domain – N-terminus
Response generated by modification of

37. Drug Targets- Receptors
Ligand
binding
domain
Effector
domain

38. 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

39. Next class…
Tomorrow (10-11 am)
Topics:
Intracellular signaling mechanism, Dose
Response Curve, Therapeutic index,
Therapeutic Window
Any queries?
Thank you!