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Genetic Makeup and Response to Drugs


Shalini S. Lynch

, PharmD, University of California San Francisco School of Pharmacy

Reviewed/Revised Jul 2022 | Modified Sep 2022
Topic Resources

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 Overview of Response to Drugs Everyone responds to drugs differently. The way a person responds to a drug is affected by many factors, including Genetic makeup Age Body size Use of other drugs and dietary supplements (such... read more 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 Drug Metabolism Drug metabolism is the chemical alteration of a drug by the body. (See also Introduction to Administration and Kinetics of Drugs.) Some drugs are chemically altered by the body (metabolized)... read more ) 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 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 Malignant Hyperthermia Malignant hyperthermia is a rare, life-threatening rise in body temperature that occurs in susceptible people who are given certain muscle-relaxing drugs plus an anesthetic gas for surgery.... read more may develop. It causes a very high fever. Muscles stiffen, the heart races, and blood pressure falls.

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