Tolerance and Resistance to Drugs

ByShalini S. Lynch, PharmD, University of California San Francisco School of Pharmacy
Reviewed/Revised Jul 2022 | Modified Oct 2022

Tolerance is a person's diminished response to a drug, which occurs when the drug is used repeatedly and the body adapts to the continued presence of the drug. Resistance refers to the ability of microorganisms or cancer cells to withstand the effects of a drug usually effective against them.

(See also Overview of Response to Drugs.)


Receptors on Cells).

Tolerance is not the same as dependence or addiction.


Strains of microorganisms (bacteria or viruses) are said to develop resistance when they are no longer killed or inhibited by the antibiotics and antiviral drugs that are usually effective against them (or, in practice, when significantly higher than normal doses are required to have an effect). Similarly, cancer cells may develop resistance to chemotherapy drugs.

Resistance appears because of the mutations that take place spontaneously in any group of growing microorganisms or cells, whether exposed to drugs or not. Most such mutations change the microorganism's or cell's structure or biochemical pathways in a way that is harmful to the microorganism or cell. But some mutations change the parts of the microorganism or cell that are affected by drugs, decreasing the drug's ability to work (that is, causing resistance). Because such mutations are very rare, there are normally only a few such resistant microorganisms or cells in any group. However, if all or many of the “normal” microorganisms or cells are killed by a drug, a much higher proportion of the survivors are likely to be resistant. If the resistant survivors are not killed by the body's natural defenses, which is more likely when drugs are stopped too soon or not taken in the proper manner, they may reproduce and pass on the resistant trait to their descendants.

Prevention and Treatment

To prevent the development of resistance, doctors try to use antibiotics only when necessary (not for viral infections such as a cold) and have people take them for a full course of treatment. In the treatment of certain serious infections, such as HIV, doctors usually give two or more different drugs at the same time because it is very unlikely that a cell would spontaneously be resistant to two drugs at the same time. However, giving one drug for a short time followed by another can produce resistance to multiple drugs. Multi-drug resistance has become a problem with tuberculosis in particular.

Once tolerance or resistance has developed to a drug, doctors may increase the dose or use a different drug.

Drugs Mentioned In This Article
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