Drug Target and Metabolism
After entering the
bloodstream, the drug is carried throughout the body to find its way
into both the intended target and unintended tissue. Drug dosages are usually calculated with the knowledge that a certain amount of the drug will be metabolized before it reaches its target. A drug such as lidocaine, given intravenously to treat a
patient who has had a heart attack, enters the heart muscle as well as fat and muscle tissue where it has no therapeutic effect. Drugs stored in fat tissue eventually reenter the
bloodstream and reach the target site. Some drugs, such as amiodarone (used for the treatment of abnormalities in the heart rhythm), are extremely soluble in fat. Even if drug administration has stopped for weeks, the drug continues to leak out of the fat and into the bloodstream, where it travels to the heart and continues to exert an effect. This is not always desirable in drugs that have toxic effects on patients, since the toxic action may continue for many months.
A drug exerts its effects for a finite period of time. Eventually some drugs are metabolized, changing either into molecules that exert much weaker effects or into others that have no effect. Metabolism of a drug involves the actions of enzymes on drug molecules, either breaking the molecules apart, or adding new chemical groups to prevent the drug from acting in the intended way. The liver contains enzymes that metabolize many different kinds of drugs as they pass through the organ, and the lungs can also metabolize drugs. Patients with diseases that affect the liver or lungs may have trouble metabolizing drugs. As a result, a drug dosage that normally has a beneficial therapeutic effect may have a toxic effect because there is more of the drug at the target site than anticipated. Once the drug molecule has been changed into an inactive form it is usually removed from the bloodstream by the kidneys and passes out of the body in the urine.
Some drugs are not altered by metabolism. The effects of these drugs are ended when they are removed from the bloodstream by the kidneys and excreted in the urine. A patient who has poor kidney function because of renal disease may suffer from the toxic effect of a drug that depends on kidney excretion to terminate its effects, unless smaller amounts of the drug than usual are given to the patient. Drugs can also be removed from the body unaltered by the lungs; anesthetic drugs are usually not metabolized but are removed in the expired air. The rate of breathing governs the time course of drug removal. A patient who has depressed respiration after surgery might not wake up from anesthesia as quickly as a patient with a normal rate of breathing.