1. UNIT I: Introduction to Pharmacology Chapter 2 Drug-Receptor Interactions and Pharmacodynamics

2. I. OVERVIEW Chapter 2: Drug-Receptor Interactions and Pharmacodynamics Dose Effect Absorption Distribution Metabolism Elimination Drug interactions Tissue/organ sensitivity (target status) What is pharmacodynamics? Effect site Concentration Pharmacokinetics Pharmacodynamics

4. Chapter 2: Drug-Receptor Interactions and Pharmacodynamics

17. a. Occupation theory D + R  DR  RESPONSE :response is proportional to the fraction of occupied receptors :maximal response occurs when all the receptors are occupied Chapter 2: Drug-Receptor Interactions and Pharmacodynamics

22. Chapter 2: Drug-Receptor Interactions and Pharmacodynamics

27. Chapter 2: Drug-Receptor Interactions and Pharmacodynamics k 1 k 2 Drug Receptor Effect Drug-Receptor Complex Ligand-binding domain Effector domain Drug(Ligand)  Receptor interaction Langley (1878) Effect D+R DR k 1 k 2

35. Agonists differing in potency and maximum efficacy Chapter 2: Drug-Receptor Interactions and Pharmacodynamics

36. PARTIAL AGONISTS - EFFICACY Even though drugs may occupy the same # of receptors, the magnitude of their effects may differ. Chapter 2: Drug-Receptor Interactions and Pharmacodynamics [D] (concentration units) % Maximal Effect 0.01 0.10 1.00 10.00 100.00 1000.00 0.0 0.2 0.4 0.6 0.8 1.0 Partial agonist Full Agonist Partial agonist

42. AGONIST VS ANTAGONIST Chapter 2: Drug-Receptor Interactions and Pharmacodynamics

43. Chapter 2: Drug-Receptor Interactions and Pharmacodynamics

44. What happen when you increase agonist concentration even higher Chapter 2: Drug-Receptor Interactions and Pharmacodynamics

45. How do non competitive antagonist affect receptor function Chapter 2: Drug-Receptor Interactions and Pharmacodynamics

46. Chapter 2: Drug-Receptor Interactions and Pharmacodynamics

48. Chapter 2: Drug-Receptor Interactions and Pharmacodynamics Endpoints to monitor drug effects Farnesyltransferase inhibitors for cancer LEVEL ENDPOINT Molecular Farnesyltransferase inhibition Cellular Proliferation rate, Apoptosis Tumor Response (Change in tumor size) Organism Survival, Quality of life

51. Chapter 2: Drug-Receptor Interactions and Pharmacodynamics Determinants of Drug Activity 1. Potency: the amount of drug to produce an effect of a given magnitude 2. Efficacy: the maximal response (effect) produced by drug Biologic effect Log dose potency efficacy 0 50 100 Biologic effect(%) Log dose (mg) 1 10 100 Morphine Codeine Aspirin

59. Chapter 2: Drug-Receptor Interactions and Pharmacodynamics Quiz on Monday (Chap 1 & 2)