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 ~

Behavior

Drug amount (dose)

min

max

lo hi

Peak Effects as Function of Dose

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 ~

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. ~

Percentage Responding

Percentage of population affected > threshold response As function of drug dose

NOT magnitude of drug effects ~

Response Magnitude

Average response magnitude in population

percentage of maximum response as function of drug dose ~

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 ~

100

50

0

DRUG DOSE0 X

ED50

% population

ED50 = effective dose in 50% of population

Dose-Response Curve: % Population

ED100

LD50 = lethal dose in 50% of population ~

Effect magnitude information ~

% MaximumResponse

0

DRUG DOSE0 X

100

Drug Response Curve: Magnitude

A

B

50

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 ~

DRUG DOSE0 X

Maximum Efficacy

B has greater max efficacy than A ~

A

B

% MaximumResponse

0

100

50

DRUG DOSE0 X

Potency

A is more potent than B ~

A

B

% MaximumResponse

0

100

50

Predicting Drug Effects

Response magnitude Dose-response Curve

represents mean from groups Predict individual’s response to

drug? Variability standard error of the mean ~

DRUG DOSE0 X

Standard Error

Gives idea of response range Prediction represents probability ~

% MaximumResponse

0

100

50

Margin of safety % population responding

Compare effective dose (ED50) to

Lethal dose (LD50)

Or toxic dose (TD50)

Therapeutic Index

TI: 10mg/10mg = 1

100mg/10mg = 10

1000mg/10mg = 100 ~

LD50

ED50

100

50

0

DRUG DOSE0 X

ED LD

% Population

TI = LD50/ ED50

Relatively safe ~

100

50

0

DRUG DOSE0 X

ED LD

% Population

TI = LD50/ ED50

Less safe drug ~

100

50

0

DRUG DOSE0 X

ED

LD

% Population

Slope of curve important ~

Drug effects other than desired effects Drugs have multiple effects! TD50 : toxic dose

TI for side effects

Therapeutic Index: Side Effects

TD50 side effect

ED50 desired effect

Comparing different variables same drug

100

50

0

DRUG DOSE0 X

A B

% population

sex, age, etc.

or tolerance ~