Therapeutic Index

When the dose of a drug is increased progressively, the desired response in the patient usually rises to a maximum beyond which further increases in dose elicit no greater benefit but induce only unwanted effects. This is because a drug does not have a single dose-response curve, but a different curve for each action, wanted as well as unwanted. New and unwanted actions are recruited if dose is increased after the maximum therapeutic effect has been achieved.

A sympathomimetic bronchodilator might exhibit one dose-response relation for decreasing airways resistance (wanted) and another for increase in heart rate (unwanted). Clearly the usefulness of any drug is intimately related to the extent to which such dose-response relations can be separated. Ehrlich (p. 201) introduced the concept of the therapeutic index or ratio as the maximum tolerated dose divided by the minimum curative dose but, since such single doses cannot be determined accurately, the index is never calculated in this way in man. More realistically, a dose that has some unwanted effect in 50% of humans, e.g. a specified increase in heart rate (in the case of an adrenoceptor agonist bronchodilator) can be related to that which is therapeutic in 50% (ED50), e.g. a specified decrease in airways resistance (in practice such information is not available for many drugs). Nevertheless the therapeutic index does embody a concept that is fundamental in comparing the usefulness of one drug with another, namely, safety in relation to efficacy. The concept is expressed diagrammatically in Figure 7.1.

Does Response Curve Ed50

Dose

Fig. 7.1 Dose-response curves for two hypothetical drugs. Drug X:the dose that brings about the maximum wanted effect is less than the lowest dose that produces the unwanted effect.The ratio ED50 (unwanted effect)/ED50 (wanted effect) indicates that drug X has a large therapeutic index: it is thus highly selective in its wanted action. DrugY causes unwanted effects at doses well below those which produce its maximum benefit-The ratio ED50 (unwanted effect)/ED50 (wanted effect) indicates that the drug has a small therapeutic index: it is thus nonselective.

Dose

Fig. 7.1 Dose-response curves for two hypothetical drugs. Drug X:the dose that brings about the maximum wanted effect is less than the lowest dose that produces the unwanted effect.The ratio ED50 (unwanted effect)/ED50 (wanted effect) indicates that drug X has a large therapeutic index: it is thus highly selective in its wanted action. DrugY causes unwanted effects at doses well below those which produce its maximum benefit-The ratio ED50 (unwanted effect)/ED50 (wanted effect) indicates that the drug has a small therapeutic index: it is thus nonselective.

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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Responses

  • Asfaha
    Does response curve ED50?
    6 years ago

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