Therapeutic Window Phenomenon

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Chapter: Essential pharmacology : Pharmacodynamics Mechanism Of Drug Action; Receptor Pharmacology

This is an unusual feature seen with certain drugs: optimal therapeutic effect is exerted only over a narrow range of plasma drug concentrations or drug doses; both below and above this range, beneficial effects are suboptimal, i.e., the effect declines if the doses are increased beyond a certain level.


THERAPEUTIC  WINDOW  PHENOMENON

 

This is an unusual feature seen with certain drugs: optimal therapeutic effect is exerted only over a narrow range of plasma drug concentrations or drug doses; both below and above this range, beneficial effects are suboptimal, i.e., the effect declines if the doses are increased beyond a certain level. Examples are:

 

§ Tricyclics (imipramine etc.) exert maximal antidepressant effect when their plasma concentration is maintained between 50–150 ng/ml.

 

§ Clonidine lowers BP over a plasma concentration range of 0.2–2.0 ng/ml; BP may rise at concentrations above 2 ng/ml.

 

§ Glipizide exerts poorer glycaemia control at doses > 25 mg/day.

 

The pharmacological basis of this phenomenon is not well understood, but may be due to dual or complex actions of the drug—different facets of which become prominent at different concentrations.

 

The log doseresponse curve (DRC) can be characterized by its shape (slope and maxima) and position on the dose axis.

 

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