Tolerance is a person's diminished response to a medication or substance, which occurs when the medication or substance is used repeatedly and the body adapts to the continued presence of the medication or substance. Resistance refers to the ability of microorganisms or cancer cells to withstand the effects of a medication usually effective against them.
(See also Overview of Response to Drugs and Medications.)
Tolerance
A person may develop tolerance to a medication or substance when used repeatedly. For instance, when morphine or alcohol is used for a long time, larger and larger doses must be taken to produce the same effect. Usually, tolerance develops because metabolism of the medication or substance speeds up (often because the liver enzymes involved in metabolizing medications and substances become more active) and because the number of sites (cell receptors) that the medication or substance attaches to or the strength of the bond (affinity) between the receptor and medication or substance decreases (see A person may develop tolerance to a medication or substance when used repeatedly. For instance, when morphine or alcohol is used for a long time, larger and larger doses must be taken to produce the same effect. Usually, tolerance develops because metabolism of the medication or substance speeds up (often because the liver enzymes involved in metabolizing medications and substances become more active) and because the number of sites (cell receptors) that the medication or substance attaches to or the strength of the bond (affinity) between the receptor and medication or substance decreases (seeReceptors on Cells).
Tolerance is not the same as dependence or addiction.
Resistance
Strains of microorganisms (bacteria or viruses) are said to develop resistance when they are no longer killed or inhibited by the antibiotics and antiviral medications 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 medications 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 medications, decreasing the medication'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 medication, 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 medications 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 medications at the same time because it is very unlikely that a cell would spontaneously be resistant to two medications at the same time. However, giving one medication for a short time followed by another can produce resistance to multiple medications. Multidrug resistance has become a problem with tuberculosis in particular.
Once tolerance or resistance has developed to a medication, doctors may increase the dose or use a different medication.
