The document discusses dose-response relationships, which relate the amount of a drug administered (dose) to its biological effect (response). It defines key terms like dose, response, dose-response curve, potency, efficacy, and therapeutic index. Dose-response curves can take different shapes depending on whether response is measured quantally or gradually, and can be used to determine a drug's potency, efficacy, and margin of safety between therapeutic and toxic doses.

1. Dose-Response Relationship
Efficacy and Toxicity evaluation,
Dose-response analysis,
Margin of safety

2. What is a dose response relationship?
What is a Dose Response Curve (DRC)?
The dose and response is closely related
to each other and this relationship is called
as Dose response relationship.

3. ❑ ‘Dose’ is the amount of drug to administered to produce a certain degree of
response in a patient.
❑ Dose- Response relationship has two components:
1. Dose-plasma concentration relationship
2. Plasma concentration-response relationship
❑ ‘Response’: The change in activity of the cell or tissue produce by the
selected dose of the drug is called the response.
Dose Response Curve (DRC):

4. Shape of the curve

5. Is there any relationship between
shape of curve and potency
Reason for steep curve

6. DRC is used to predict:
DRUG POTENCY
❑ The position of DRC on the axis is an
index of drug potency.
❑ A DRC positioned rightward indicates
lower potency. Drug A is more potent
than Drug B, since it produced intensity
of response as Drug B as much smaller
doses.
❑ The relative potency is determined by
comparing the dose of two agonists at
which they produces half maximum
response (EC50).
❑ Ex. 10mg of morphine is equivalent
100mg of pethidine to produce
analgesia, hence morphine is 10 times
more potent than pethidine

7. ❑ The upper limit of DRC is the index of drug efficacy and
refers to the maximal response that can be elicited by the
drug, Ex. morphine produce a degree of analgesia not
obtain with any dose of aspirin.
❑ Morphine is more efficacious than aspirin.
❑ Efficacy is a more decisive factor in the choice of the drug.
DRUG EFFICACY:
Log DRC for efficacy of Drug A and B

8. Types of Dose Response Curve:
Example: Consider a situation where a new compound is to be tested in
a clinical trial for its ability to reduce blood pressure. The outcome of
treatment can be plotted as response vs log. Dose, where response is
measured in one of two ways:
(i) As reduction in blood pressure in absolute terms. This will give a
graded dose-response curve.
(ii) As % of all individuals classified as responders, where responders
are defined as those individuals who have attained a preselected
drop in blood pressure. This will give a quantal dose-response
curve

10. Quantal (All or None) Dose Response Curve:

14. ❑ The slope of the upper part of the curve is
useful in assessing the relative safety of
drug.
❑ Ex: Most CNS depressants have steep
slope which indicates a narrow margin of
safety between the dose that produces
sedation and the dose that produces coma.
❑ The drug with more shallow slope of curve
produces little increase in response over a
wide dose range and has greater margin of
safety.
❑ Dose individualization is required for use of
such drug to avoid toxic effect.

15. Therapeutic Index:
❑ A statement of relative safety of a drug.
❑ The gap between the therapeutic effect DRC and the
adverse effect DRC defines Therapeutic Index of a
drug.
❑ Quantal dose effect curves permit an analysis of the
margin of safety (or selectivity in response) for a
specific drug. In animal studies, the therapeutic index
is defined as the ratio of the TD50 to ED50.
❑ Median Effective Dose (ED50): The dose at which
50% of individuals show the specified quantal effect.
❑ Median Toxic dose (TD50): The dose required to
produce a particular toxic effect in 50% of animals
❑ Median Lethal Dose (LD50): If the toxic effect in 50%
of animals is death

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