1. IN THE NAME OF GOD

2. Principles of pharmacodynamics
Introduction
What is pharmacology
Principles of pharmacodynamics
Mechanism of Drug Actions
Drug-Receptor Interaction
Classification of Drugs
Dose-Response Relationships

3. The science that deals with:
What is Pharmacology?
Pharmakon = a drug or poison
Logos = discourse or study
The science that deals with:
The fate of drugs in the body
Pharmacokinetics
The actions of drugs on the body
Pharmacodynamics

4. Pharmacotherapeutics
Pharmacy
The science of preparation
of drugs
Pharmacotherapeutics
The treatment of diseases by drugs

5. Textbooks Basic & Clinical Pharmacology, 2004 Bertram G. Katzung
Goodman and Gilman’s The pharmacological basis of therapeutics, 2001
(J.G. Hardman and L.E. Limbard, eds.) New York: McGraw-Hill
(first published in 1941)

6. Principles of Pharmacodynamics

7. Why to study Pharmacodynamics?
Mechanisms of drug action
& the relationship between
drug concentration and effect
Why to study Pharmacodynamics?
Scientific basis for the
selection & use of drugs

8. Mechanism of Drug Action
Basic Concept
Interaction of a drug with its target tissue involves specific binding sites
Receptor
A macromolecular component of the cell to which the drug binds and leads to an effect on the cell
Nonspecific binding site
A biological component to which the drug binds but does not lead to any effect

9. Nature of Drug Receptors
Proteins
Transmembrane proteins
Receptors for neurotransmitters
Transport proteins
Na+/K+ ATPase digitalis glycosides
Ion channels benzodiazepines
Structural proteins
Tubulin colchicine
Enzymes
Cycloxygenase acetylsalicylic acid
ACE Captopril

10. Non-protein drug receptors
Lipids
Anesthetics
Nystatin, Amphotericin
Nucleotides
Antineoplastic drugs
Cyclophosphamide

11. Other Sites of Drug Action
Water
Osmotic Diuretics & Laxatives
Ions
Antacids
Changing urine pH
Chelators
Dimercaprol Hg+2 , As+2
Penicillamine Cu+2
EDTA Pb2

12. Drug-Receptor Interaction

13. Drug-Receptor InteractionK1
R + D R-D Effect
Affinity
The tendency of a drug to combine
with its receptor Kd
The concentration of drug that binds to 50% of the receptors
Affinity= the reciprocal of the Kd K2

14. Drug-Receptor InteractionK1
R + D R-D Effect
Intrinsic Activity
The ability of a drug to initiate a cellular effect K2

15. Receptor-Effector Coupling
Receptor conformational change
Coupling Efficiency

16. Drug-Receptor Binding

17. Concentration-Effect Relationship

18. Classification of drugs
Agonist
Full agonist
Partial agonist
Antagonist
Competitive antagonist
Non-competitive antagonist

19. Other Drug Antagonism Chemical antagonists Physiologic antagonism
Heparin & protamine
Physiologic antagonism
Glucocorticoids & Insulin

20. Dose-Response Relationship
Graded dose-response
Quantal dose-response

21. Graded Dose-Response Relationship

22. Sigmoidal D-R Curve

23. Graded Dose-Response Relations
Potency
Efficacy

24. Relative potency

25. Relative Efficacy

26. Agonists with different potency

27. Agonists with different efficacy

28. Competitive Antagonism

29. D-R Curve for Competitive Antagonists

30. Non-Competitive Antagonism

31. Quantal D-R Curve

32. Quantal D-R Curve

33. Quantal D-R Curve

34. Quantal-Dose Response
Median Effective Dose (ED50)
Median Toxic Dose (TD50)
Median Lethal Dose (LD50)
Therapeutic index
LD50/ED50 or TD50/ED50

35. Signaling Mechanisms & Drug Action

36. Transmembrane Signaling
Intracellular receptors
Enzyme-linked receptors
Ligand-gated ion channels
G-protein-coupled receptors

37. Intracellular Receptors
Steroid Receptor Superfamily
Glucocorticoids
Mineralocorticoids
Sex hormones
Vitamin D
Thyroid hormone
Retinoic Acid

40. Therapeutically important consequences
Slow onset of action
Persistence of effect following withdrawal of the drug

41. Enzyme-Linked Receptors
Receptor Tyrosine Kinases
Insulin
Epidermal growth factor (EGF)
Platelet-derived growth factor (PDGF)

42. Receptor Tyrosine Kinases

43. Enzyme-Linked Receptors
Receptor Guanylyl Cyclase
Atrial natriuretic factor (ANF)
cGMP (Natriuresis; Vasodilation)
Receptor Serine Kinase
Transforming growth factor-beta (TGF-b)
Cytokine Receptors

44. Cytokine Receptor

45. Ligand-gated Ion Channels
Acetylcholine nicotinic receptors
Neuromuscular blocking drugs (tubucurarine)
Ganglion blockers (Mecamylamine)
GABAA
Benzodiazepines (sedative-hypnotic)
Glutamate
Topiramate (anticonvulsant)

46. Ligand-gated Ion Channels

47. G Protein-Coupled Receptors