DOSE-RESPONSE CURVE

By Dr. Maria Khurshid

 Dose
 Dose is the amount of drug administered to
produce a certain degree of response in a
patient.

 Dose of drug measured milligrams(mg) or

millimols(mmol)
 Response
 The change in activity of the cell or tissue
produce by the selected dose of the drug is
called the response
 The dose and response is closely related to
each other and this relationship is called as
Dose response relationship.

 A typical curve showing the dose response

relationship is called dose response curve
(DRC).
What is dose response curve?
 The DRC of drug is useful to predict potency,
efficacy & safety of drug.

 If the dose is plotted on x-axis and response

on y-axis.

 A dose response curve is obtained that is

mostly S- shaped in semilog plots.
Types of DRC
 There are two types of DRC

1. Graded dose response curve

2. Quantal dose response curve

% Responders
response

dose
dose
Graded Dose-Response Relations
 In graded dose response curve, the relation between many
graded doses and their respective responses is observed in
single individual.

 Pharmacologic effect (response) is proportional to dose i.e

the concentration of a drug increases, the pharmacologic
effect also increases until all receptors are occupied.
 For example: in blood pressure
smaller doses antihypertensive drugs little or no change
in blood pressure

Graded ↑ in drug concentrations response will be increase

by decreasing blood pressure by 5mmhg, 8mmhg, 10mmhg,
18mmhg
x axis: Dose or concentration
 y axis: Response

 Shape of log dose response curve is

sigmoidal
 INFORMATION OBTAINED FROM GRADED DOSE
RESPONSE CURVE

 Two important properties can be obtained

from GD response curve
I. Potency
II. Efficacy
Potency
 Is amount of drug necessary to produce an effect of given
magnitude

 Median effective concentration (EC50): the effective conc.

Of drug producing 50% of maximal response is usually
used to determine potency. Less EC50, more potent the
drug & vice versa

For example: 10mg of Morphine is equivalent 100mg of

Pethidine to produce analgesia, hence morphine is 10 times
more potent than pethidine.
Efficacy

 Efficacy is the magnitude of response a drug causes when it

interacts with receptor.

 It is dependent on the number of drug-receptor complexes

formed and its intrinsic activity.
 Quantal Dose-Response Relations
 Quantal dose relation is between the dose of drug and the
proportion of a population that responds to it.

 The response observed is binary i.e “either present-or

absent ” in single individual.
  For example, after the administration of a hypnotic drug, a
patient is either asleep or not.
 It is often characterized by stating the median effective dose
(ED50) which is a dose at which 50% of individuals exhibit
specified quantal effect.

 x axis: Drug Dose

 y axis :Percentage of population responding
Construction of dose-response curves for
quantal responses requires the use of
populations of subjects who are
characterized by interindividual variability
. A few subjects demonstrate an initial
response at a low dose, most subjects
demonstrate an initial response at an
intermediate dose, and a few subjects
demonstrate an initial response at a high
dose, resulting in a bell-shaped “Gaussian”
distribution of sensitivity.
Quantal dose-response curves are often
plotted in a cumulative manner, comparing
the dose of drug on the x-axis with the
cumulative percentage of subjects
responding to that dose on the y-axis 
GRADED DRC QUANTAL DRC
Individual person population
Relationship among dose Among dose and
and response responders
Information about Information about margin
potency and efficacy of safety, therapeutic
index, therapeutic
window
Response is graded Response is quantal
“either-or” and “all or
none”
Graph Graph
 INFORMATION OBTAINED FROM QUANTAL
DOSE RESPONSE CURVE
 It is useful in predicting safety of drug.

 ED50 OR TD50:In quantal dose-response curves,

the concentration or dose that causes a
specified(therapeutic or toxic) response in
50% of the population under study
 Therapeutic index: It is used to measure the relative safety of
the drug

TI=

if TI high or wide(DRcurve) →drug is safe

if TI low or narrow(DRcurve)→drugs are dangerous

Example: drugs with low TI are Lithium, Warfarin and digoxin.

 Important definition related to Dose
Response curve
• EC - Effective Concentration (e.g. EC50-median effective
concentration : the drug concentration producing 50% of a
maximal effect).

• ED - Effective Dose (e.g. ED50-median effective dose: the

drug dose producing 50% of a maximal effect in Graded D-R curve; or
alternatively the dose producing the desired effect in 50% of the
population in Quantal D-R curve.
• Example: administering a 1000 mg dose of acetaminophen (ED50)
orally will result in a plasma concentration of 15 ug/ml (EC50), which
produces effective pain relief in 50% of adult patients.
 Important definition related to Dose
Response curve
• TD - Toxic Dose (e.g. TD50: the dose producing a toxic effect in 50% of
the population).

• LD - Lethal Dose (e.g. LD50: the dose producing a lethal effect in 50% of
the population). LD values almost always refer to animal studies, since
lethal doses in humans are rarely known with any accuracy.
 SUMMARY

 A graded dose-response relationship is in an individual

 A quantal dose-response relationship in the population.

 Graded doses of a drug given to an individual usually result in a

greater magnitude of response as the dose increases.

 In a quantal dose-response relationship, the percentage of the

population affected increases as the dose is increased; the
relationship is quantal in that the effect is judged to be either
present or absent in a given individual."
THANK
YOU