Pharmacodyn

amics

Dose-Response
Curves

Dr. Aung Kyaw Moe

Learning Outcomes
1. List types of dose-response curve
2. Describe graded and quantal dose-response curve
3. Compare the efficacy and potency of 2 drugs on the
basis of their dose-response curves
4. Describe the effect of antagonist on dose-response curve
of agonist
5. Understand half maximal effective concentration
(EC50), median effective dose (ED50), median lethal
dose (LD50), median toxic dose (TD50), therapeutic
index, therapeutic window

Graded
Continuous scale
Measured in a single biologic unit
Relates dose to intensity of effect

Quantal
All-or-none pharmacologic effect
Population studies
Relates dose to frequency of effect

Graded dose-response curve

A graph of the relationship between dose & magnitude of response
X-axis -- independent variable: Dose
Y-axis -- dependent variable : magnitude of response
Graded dose-response curve shows response on a continuous & gradual
scale and the intensity of the effect is proportional to the dose

doses - arithmetic scale

dose-response curve - hyperbolic

doses - logarithmic scale

dose-response curve - Sigmoid
Cover a broad concentration range

 Efficacy

Observation

- ability of a drug to elicit a response when it interacts with a receptor

- refers to the maximum response (Emax) achievable from a drug

Potency
- a measure of the amount of drug necessary to produce an effect of a given
magnitude
EC50 potency
- half maximal effective concentration (EC50) is used to determine potency
- EC50: concentration of drug producing an effect that is 50% of the maximum

O Non-competitive antagonist -

50%

drug efficacy
(change the slope & level of
maximum response,
cause downward shift of the
maximum)

O Reversible competitive

antagonist
- efficacy is unchanged,
- drug potency
(the curve is shifted to right)

Quantal dose-response curve

Performed on a population of subjects

Curve showing cumulative frequency distribution of responders vs. dose
Y- axis: number or % of individuals responding
Does not measure magnitude of drug effects
Specific effect/ degree of response is predefined, determine the % of
population affected

Purpose
To allow predictions about what proportion of a population of subjects will
respond to given doses of the drug

Problem:
- Many units (animals, humans, organs) required to create a quantal dose-effect curve

Differences:
-Graded: How much response can I get if I give this dose
-Quantal: How many subjects will give a response that I want to see if I give this dose

Median effective dose (ED50):

Dose required to produce
therapeutic effect in 50% of
the test subject population

Quantal dose-response:
- e.g. Selected response: at least 20% reduce in diastolic blood pressure
Dose of drug A Number (frequency) of
(mg/kg)
individuals giving the response

Cumulated number (frequency) of

individuals giving the response

10

20

30

11

20

Median effective dose

(ED50)
Median toxic dose
(TD50)
Median lethal dose
(LD50)

Dose required to produce therapeutic effect in 50% of the test

subject population
Dose required to produce toxic effect in 50% of the test subject
population
Dose required to cause death in 50% of the test subject
population

Therapeutic Index
Is the ratio of the dose that produces toxicity to the dose that
produces a clinically desired response
Drug with high therapeutic index has wide therapeutic window

Therapeutic window: the range of drug dosages which can treat

disease effectively with minimal or no signs of toxicity

Quantal relationships can be defined for both toxic and therapeutic drug effects to allow calculation of the therapeutic index (TI)
and the certain safety factor (CSF) of a drug. The TI and CSF are based on the difference between the toxic dose and the
therapeutic dose in a population of subjects. The TI is defined as the ratio between the median lethal dose (LD50) and the ED50. It
provides a general indication of the margin of safety of a drug, but the CSF is a more realistic estimate of drug safety (see Fig. 36). The CSF is defined as the ratio between the dose that is lethal in 1% of subjects (LD1) and the dose that produces a therapeutic
effect in 99% of subjects (ED99). When phenobarbital was tested in animals, for example, it was found to have a TI of 10 and a CSF
of 2. Because the dose that will kill 1% of animals is twice the dose that is required to produce the therapeutic effect in 99% of
animals, the drug has a good margin of safety.

The range between the minimum toxic dose and the

minimum therapeutic dose is called the therapeutic window
and is of greater practical value in choosing the dose for a
patient.

The clinically acceptable risk of

toxicity depends critically on the
severity of the disease being treated.