1. MEDC 603 Fall 20071 Measuring Drug Action  Dose – Response Curves Response  fraction bound (fb) = Fraction bound [D] 1.0 0.0 0.5 [D] = K D R + D R:D Response KDKD KAKA

2. MEDC 603 Fall 20072 Measuring Drug Action  Dose – Response Curves D in system ‘R:D’ Response IC 50 or EC 50 or LD 50 Agonist: An agent that facilitates or enhances the normal action of a receptor. Antagonist: An agent that prevents the normal action of a receptor. 50% Or Log [agonist] O 90% IC 90 or EC 90 or LD 90 Inhibition Concentration Effective Concentration Lethal Dose

3. MEDC 603 Fall 20073 Measuring Drug Action  Dose – Response Curves Drug 1 Drug 2

4. MEDC 603 Fall 20074 Measuring Drug Action  Efficacy and Potency …… Potency corresponds to the strength of a drug, while Efficacy corresponds to the effectiveness of a drug. …… e.g., if 1 mg of drug A relieves pain as effectively as 10 mg of drug B, drug A is twice as potent as drug B …… the diuretic furosemide eliminates much more salt and water through urine than does the diuretic chlorothiazide. Thus, furosemide has greater efficacy than chlorothiazide.

5. MEDC 603 Fall 20075 Measuring Drug Action  Efficacy / Potency / Toxicity Desired Response (%) Toxicity (%) 100 50 0 100 50 0 Log [Drug] Blue lines …. Drug 1 Red lines …. Drug 2 Solid lines …. Desired response Dotted lines …. Toxicity response

6. MEDC 603 Fall 20076 Measuring Drug Action  How are these drug-response profiles generated? e.g., anticoagulants and inhibition of pro-coagulant enzymes T S S T S S Anticoagulant Color Development = Activity of Enzyme Time (s) [A] =0 [A] = max Inhibition of Enz: Log [anticoagulant] K I or IC 50

7. MEDC 603 Fall 20077  Cellular/Pharmacological assays Cell Viability Assay Drug Mouse Tail Flick Assay Drug Heat!  How are these drug-response profiles generated? Measuring Drug Action

8. MEDC 603 Fall 20078  High Throughput Screening Assays 96-well microtiter plate  Simultaneous …. 96- or 384-well microtiter plates …. robotic analysis  Chromogenic substrates …. develop color  Yes or No answer ….. fixed concentration of drug  Quantitative …. may also give you K I values!!  How are these drug-response profiles generated? Measuring Drug Action