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Dose-Response Relationships

Dose-Response Relationships . Lesson 6. Dose & Drug Effects. Pharmacodynamics what the drug does to the body Effects of drug depends on dose In general... as dose increases, effects increase to a maximum then effects decrease ~. Peak Effects as Function of Dose. max. Behavior.

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Dose-Response Relationships

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  1. Dose-Response Relationships Lesson 6

  2. Dose & Drug Effects • Pharmacodynamics • what the drug does to the body • Effects of drug depends on dose • In general... as dose increases, effects increase to a maximum then effects decrease ~

  3. Peak Effects as Function of Dose max Behavior min lo hi Drug amount (dose)

  4. Dose-response Relationship • Weight of individual important • Dose • amount of drug per body weight • mg/kg • milligrams/kilogram • Helps achieve equal blood concentrations • often not tightly controlled in humans ~

  5. Dose-response Relationship • Drug effects are variable • Probability statements • Group dose-response curves • % of population responding • Response magnitude • Different for each individual effect • i.e., temperature, respiration, euphoria, etc. ~

  6. Percentage Responding • Percentage of population affected • > threshold response • As function of drug dose • NOT magnitude of drug effects ~

  7. Response Magnitude • Average response magnitude • in population • percentage of maximum response • as function of drug dose ~

  8. Dose-Response Curve • How response changes as function of dose • S-shaped curves • Slope important • Gradual •  dose  small response change • Steep •  dose  large response change ~

  9. ED100 ED50 Dose-Response Curve: % Population 100 • ED50 = effective dose in 50% of population % population 50 0 0 X DRUG DOSE • LD50 = lethal dose in 50% of population ~

  10. B A Drug Response Curve: Magnitude • Effect magnitude information ~ 100 % Maximum Response 50 0 0 X DRUG DOSE

  11. Potency vs. Efficacy • Potency • relative term • drug A has same effect as drug B... but at lower dose • Maximum efficacy • maximum response magnitude • more drug  no effect if increased • but might increase side effects ~

  12. B A Maximum Efficacy 100 • B has greater max efficacy than A ~ % Maximum Response 50 0 0 X DRUG DOSE

  13. B A Potency 100 • A is more potent than B ~ % Maximum Response 50 0 0 X DRUG DOSE

  14. Predicting Drug Effects • Response magnitude • Dose-response Curve • represents mean from groups • Predict individual’s response to drug? • Variability • standard error of the mean ~

  15. Standard Error 100 • Gives idea of response range • Prediction represents probability ~ % Maximum Response 50 0 0 X DRUG DOSE

  16. Therapeutic Index • Margin of safety • % population responding • Compare effective dose (ED50) to • Lethal dose (LD50) • Or toxic dose (TD50) LD50 ED50 • TI: 10mg/10mg = 1 100mg/10mg = 10 1000mg/10mg = 100 ~

  17. TI = LD50/ ED50 ED LD • Relatively safe ~ 100 % Population 50 0 0 X DRUG DOSE

  18. TI = LD50/ ED50 ED LD • Less safe drug ~ 100 % Population 50 0 0 X DRUG DOSE

  19. Slope of curve important ~ 100 ED LD % Population 50 0 0 X DRUG DOSE

  20. TD50 side effect ED50 desired effect Therapeutic Index: Side Effects • Drug effects other than desired effects • Drugs have multiple effects! • TD50 : toxic dose • TI for side effects

  21. A B • Comparing different variables • same drug 100 % population 50 0 0 X DRUG DOSE • sex, age, etc. • or tolerance ~

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