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Tolerance and Resistance

By

Shalini S. Lynch

, PharmD, University of California San Francisco School of Pharmacy

Last full review/revision Jul 2019| Content last modified Jul 2019
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Tolerance is a decrease in response to a drug that is used repeatedly. Resistance is development of the ability to withstand the previously destructive effect of a drug by microorganisms or tumor cells.

Examples of drugs that result in tolerance include alcohol and opioids. One mechanism responsible for tolerance is accelerated metabolism, for example, by induction of hepatic enzymes such as the cytochrome P-450 system enzymes Drug Metabolism The liver is the principal site of drug metabolism (for review, see [1]). Although metabolism typically inactivates drugs, some drug metabolites are pharmacologically active—sometimes even more... read more . Generally, tolerance leads to increasing doses of a drug being required to produce the same effect. Other possible mechanisms are a decrease in binding affinity between a drug and receptor and a decrease in the number of receptors. The mechanisms responsible for drug tolerance are not always known.

Examples of resistance include the following:

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