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

MEDC 603 Fall 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

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

MEDC 603 Fall 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.

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

MEDC 603 Fall 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

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

MEDC 603 Fall  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