Dose-Response Relationships Lesson 6

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

Behavior Drug amount (dose) min max lohi Peak Effects as Function of Dose

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

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

Percentage Responding n Percentage of population affected l > threshold response l As function of drug dose n NOT magnitude of drug effects ~

Response Magnitude n Average response magnitude u in population l percentage of maximum response l as function of drug dose ~

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

DRUG DOSE 0X Response Dose-Response Curve: Slope

DRUG DOSE 0X ED 50 % population n ED 50 = effective dose in 50% of population Dose-Response Curve: % Population ED 100 n LD 50 = lethal dose in 50% of population ~

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

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

DRUG DOSE 0X Maximum Efficacy n B has greater max efficacy than A ~ A B % Maximum Response

DRUG DOSE 0X Potency n A is more potent than B ~ A B % Maximum Response

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

DRUG DOSE 0X Standard Error n Gives idea of response range l Prediction represents probability ~ % Maximum Response

n Margin of safety l % population responding n Compare effective dose (ED 50 ) to l Lethal dose (LD 50 ) l Or toxic dose (TD 50 ) Therapeutic Index n TI: 10mg/10mg = 1 100mg/10mg = mg/10mg = 100 ~ LD 50 ED 50

DRUG DOSE 0X EDLD % Population TI = LD 50 / ED 50 n Relatively safe ~

DRUG DOSE 0X EDLD % Population TI = LD 50 / ED 50 n Less safe drug ~

DRUG DOSE 0X ED LD % Population n Slope of curve important ~

n Drug effects other than desired effects l Drugs have multiple effects! l TD 50 : toxic dose n TI for side effects Therapeutic Index: Side Effects TD 50 side effect ED 50 desired effect

n Comparing different variables u same drug DRUG DOSE 0X AB % population n sex, age, etc. n or tolerance ~