Crosstolerance And Crossdependence

The term acquired tolerance is applied to tolerance developing to the actions of the same drug that has been administered repeatedly. However, if a second drug has actions similar to those of the first, an individual who becomes tolerant to the first drug is usually also tolerant to the second drug, even on the first occasion when the latter is used. This phenomenon is called cross-tolerance, and it may be partial or complete—it may extend to all the effects of the second drug, or only to some of them. The adaptive changes in the nervous system that give rise to acquired tolerance are believed by most researchers (though not all) to be responsible also for the development of physical dependence. Thus, an adaptive change in cell function, opposite in direction to the effect of the drug, will offset the latter when the drug is present (tolerance), but will give rise to a withdrawal sign or symptom when the drug is removed. The term neuroadaptive state has been proposed to designate all the physiological changes underlying the development of tolerance and physical dependence. If the second drug, to which cross-tolerance is present, is given during withdrawal from the first, it can prevent or suppress the withdrawal effect; this is known as cross-dependence. A related concept is that of transfer of dependence, from a first drug on which a person has become dependent to a second drug with similar effects, that has been given therapeutically to relieve the withdrawal signs produced by the first.


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Harold Kalant

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