Differences in genetic (inherited) makeup among individuals affect what the body does to a medication and what the medication does to the body. The study of genetic differences in the response to medications 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) medications slowly. As a result, a medication may accumulate in the body, causing toxicity. Other people metabolize medications so quickly that after they take a usual dose, drug levels in the blood never become high enough for the medication to be effective.
In some people in the United States, N-acetyltransferase, a liver enzyme that metabolizes certain medications, works slowly. Such people are called slow acetylators. Medications, 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 medications rapidly (fast acetylators).
Other people have low levels of pseudocholinesterase, a blood enzyme that inactivates medications 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.
Some people of African or Black American ancestry 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 medications (such as chloroquine and primaquine, which are used to treat malaria) destroy red blood cells and causehemolytic anemia.
Some 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 calledmalignant hyperthermia may develop. It causes a very high fever. Muscles stiffen, the heart races, and blood pressure falls.
