Relation Between

Drug Dose
&
Clinical Response
 Dose response curve
‘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.
o The dose and response is closely related to each other and this relationship
is called as Dose response relationship.
o There is direct relationship between dose intensity of response of the
curve. i.e. the intensity of response increases with the increase in dose.
 A typical curve showing the dose response relationship is called
dose response curve (DRC).

Fig. Dose response curve

 Slope of Dose response curve (DRC)

 Steep slope–moderate increase in dose

markedly increase the response (dose needs
individualization)

 Flat slope–little increase in response

occurs in wide range of doses (standard
dose can be given to most patients)

 Example: Hydralazine and

Hydrochlorothiazide DRC in Hypertension
 Dose-Effect Endpoints

Graded The graded dose-effect is measured on a continuous scale and

the intensity of the effect is proportional to the dose, such as
measuring the change in blood pressure after administering an
antihypertensive agent. Graded dose-effect relationships can be
measured in a single biologic unit that is exposed to a range of
doses. A graded dose-effect study relates the dose to the
intensity of the effect.

Quantal Conversely a quantal effect is an all-or-none effect such as alive

or dead, asleep or awake, pain-free or in pain. Quantal dose-
effect studies are performed in populations of subjects who are
treated with a range of doses, and dose is related to the
frequency of the all-or-none effect, such as the % of subjects
who survived.
Graded Dose-Effect Curve
The DRC is useful to predict potency, efficacy & safety of drug.

1)Potency: The amount of drug required to produce a certain response.

Relative potency is more meaningful than absolute potency

Relative potency: comparing the dose of two agonists at which they elicit half
maximal response (EC50)
E.g: 10mg of Morphine is equivalent to 100mg of Pethidine to produce
analgesia, hence morphine is 10 times more potent than Pethidine.

 Potency for therapeutic effect should increase over the potency for adverse
effects
 Potency of a drug is important to choose a dose
Fig. log dose response curve for potency of drug A & B
 2) Efficacy:
Maximal response that can be elicited by the drug
E.g: morphine produce analgesia not obtain with any dose of aspirin.
 Morphine is more efficacious than aspirin.
 Efficacy is an important factor in the choice of a drug
 Depending upon type of drug, both higher & lower efficacious drug is
clinically prefered.

Fig. Log dose response curve for efficacy of drug A & B

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

Fig. log dose response curve for safety of drug A & drug B
Therapeutic Index:
It is the ratio of the dose of drug that causes adverse effects at an
incidence/severity not compatible with the targeted indication to the dose that
leads to the desired pharmacological effect.

 Therapeutic index is general index of the drug’s safety & some patients may
display extreme sensitivity to certain drugs, eg. aspirin produces severe
hypersensitivity reaction in some patient at the therapeutic doses.

Therapeutic window:
It is the range of drug dosages which can treat disease effectively without
having toxic effects.
MTC = Minimum Toxic Concentration
MEC = Minimum Effective concentration

Fig. Therapeutic Index & Therapeutic Window

 Combined effects/response of drugs
If two/more drugs given simultaneously, they may be either indifferent to each
other or exhibit synergism/antagonism.
Synergism: Action of one drug is facilitated or increased by the other
• In a synergetic pair both drugs can have action in same direction or one may
be inactive and enhancing the effect of other
• Synergism is two types
- Additive
- Supraadditive/potentiation
Additive: Effect of two drugs in same direction and simply adds up
 Effects of drugs A+B= effect of drug A+ effect of drug B
 Side effects do not add up
Supraadditive: Effect of combination is greater than the individual effects.

Effects of drug A+B > effect of drug A+ effect of drug B

When one component given alone produces no effect, butenhances the effect
of the other.

Antagonism:
• One drug decreases or abolishes the action of the other
Effects of A+B < effect of drug A+ effect of drug B
• One drug is inactive and decreases the effect of the other. Three Types-
1. Physical
2. Chemical
3. Physiological antagonism
4. Receptor antagonism:
 Risk-benefit ratio

Judgment between estimated harm and the expected advantages.

• Estimated harms:
o Adverse effects
o Cost
o Inconvenience

• Expected Benefits:
 Relief of symptoms
 Cure
 Reduction in complications/mortality
 Improvement in quality of life
Thank you!!!!