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Genetic Makeup and Response to Drugs


Shalini S. Lynch

, PharmD, University of California San Francisco School of Pharmacy

Last full review/revision Aug 2019| Content last modified Aug 2019
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Differences in genetic (inherited) makeup among individuals affect what the body does to a drug and what the drug does to the body. The study of genetic differences in the response to drugs is called pharmacogenetics. In some cases, the level of an enzyme that metabolizes medications can be measured before starting the therapy. This should be considered before prescribing.

Because of their genetic makeup, some people process (metabolize) drugs slowly. As a result, a drug may accumulate in the body, causing toxicity. Other people metabolize drugs so quickly that after they take a usual dose, drug levels in the blood never become high enough for the drug to be effective.

In about half of the people in the United States, N-acetyltransferase, a liver enzyme that metabolizes certain drugs, works slowly. Such people are called slow acetylators. Drugs, such as isoniazid (which is used to treat tuberculosis), that are metabolized by this enzyme tend to reach higher blood levels and remain in the body longer in slow acetylators than they do in people in whom this enzyme metabolizes drugs rapidly (fast acetylators).

About 1 of 1,500 people have low levels of pseudocholinesterase, a blood enzyme that inactivates drugs such as succinylcholine, which is sometimes given to temporarily relax muscles during surgical procedures. If succinylcholine is not rapidly inactivated, muscle relaxation may be prolonged, and people may not be able to breathe on their own as soon after surgery as is usual. They may need a ventilator for an extended time.

About 10% of black men and fewer black women have a deficiency of glucose-6-phosphate dehydrogenase (G6PD), an enzyme that protects red blood cells from certain toxic chemicals. For example, in people with G6PD deficiency, some drugs (such as chloroquine and primaquine, which are used to treat malaria) destroy red blood cells and cause hemolytic anemia.

About 1 of 20,000 people have a genetic defect that makes muscles overly sensitive to certain inhaled anesthetics such as halothane, isoflurane, and sevoflurane. When such people are given one of these anesthetics with a muscle relaxant (usually succinylcholine), a life-threatening disorder called malignant hyperthermia may develop. It causes a very high fever. Muscles stiffen, the heart races, and blood pressure falls.

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Tolerance and Resistance to Drugs
Tolerance is the body’s diminished response to a drug. It occurs when certain drugs are used repeatedly, and the body adapts to their presence. People are most likely to develop tolerance to which of the following drugs when that drug is taken repeatedly over time?
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