Drug-Drug Interactions
Drug-drug interactions are changes in a drug's effects caused by another drug taken during the same time period.
Drug-drug interactions usually involve prescription drugs but can involve nonprescription (over-the-counter) drugs (see Section 2, Chapter 18)--most commonly, aspirin, antacids, and decongestants. Although many people do not consider alcohol a drug, it affects body processes and interacts with many drugs. Doctors or pharmacists can answer questions about possible alcohol and drug interactions.
The effects of drugs given during the same time period are sometimes beneficial but more often are unwanted and harmful. Types of drug-drug interactions include duplication, opposition (antagonism), and alteration of what the body does to one or both drugs.
 See the sidebar How to Reduce the Risk of Drug-Drug Interactions.
Duplication: When two drugs with the same effect are taken, their therapeutic effects and their side effects may be intensified. Duplication may occur when a person inadvertently takes two drugs, usually over-the-counter drugs, that have the same active ingredient. For example, a person may take a cold remedy and a sleep aid, both of which contain diphenhydramine, or a cold remedy and a pain reliever, both of which contain acetaminophen.
More often, duplication occurs when doctors prescribe two similar but not identical drugs. Sometimes, doctors deliberately prescribe such drugs to treat a disorder more effectively. For example, doctors may prescribe two antihypertensive drugs for a person whose high blood pressure is difficult to control. With this approach, blood pressure can be effectively lowered with fewer side effects than if one drug is prescribed at a higher dose. When treating cancer, doctors sometimes give several drugs (combination chemotherapy) to produce a better effect with fewer side effects. However, problems, sometimes severe, can develop when doctors inadvertently prescribe similar drugs. For example, excessive sedation and dizziness can occur when two doctors prescribe a sleep aid or when one prescribes a sleep aid and the other prescribes another drug that has sedative effects.
Opposition (Antagonism): Two drugs with opposing actions can interact, thereby reducing the effectiveness of one or both. For example, nonsteroidal anti-inflammatory drugs, (NSAIDs (see Section 6, Chapter 78)), such as ibuprofen, which are taken to relieve pain, may cause the body to retain salt and fluid; diuretics, such as hydrochlorothiazide and furosemide, help rid the body of excess salt and fluid. If a person takes both types of drug, the NSAID may reduce the diuretic's effectiveness. Certain beta-blockers (such as propranolol), taken to control high blood pressure and heart disease, counteract beta-adrenergic stimulants, such as albuterol, taken to manage asthma. Both types of drugs target the same cell receptors--beta-2 receptors (see Section 2, Chapter 12); one type blocks them, and the other stimulates them.
Alteration: One drug may alter how the body absorbs, distributes, metabolizes, or excretes another drug. Some drugs affect the P-450 enzyme system in the liver (which inactivates many drugs) and may cause another drug to be inactivated more quickly or more slowly than usual. For example, by increasing the activity of P-450 enzymes, barbiturates such as phenobarbital cause the anticoagulant warfarin to be inactivated more quickly and thus to be less effective when taken during the same time period. Doctors may need to increase the dose of warfarin to compensate for this effect. If phenobarbital is later discontinued, the level of warfarin may increase dramatically, increasing the risk of bleeding. In such cases, doctors monitor the person closely and adjust the dose of warfarin as needed.
Chemicals in cigarette smoke can increase the activity of some liver enzymes. As a result, smoking decreases the effectiveness of some drugs, including propoxyphene (an analgesic) and theophylline (a drug that widens the airways called a bronchodilator).
The histamine-2 (H2) blocker cimetidine (used to treat ulcers, heartburn, and gastroesophageal reflux) and the antibiotics ciprofloxacin and erythromycin may slow liver enzyme activity, prolonging the action of theophylline.
Some drugs affect the rate at which the kidneys excrete another drug. For example, large doses of vitamin C supplements increase the urine's acidity and thus may change the rate of excretion and activity of certain drugs. For example, the rate of excretion may be decreased for acidic drugs such as aspirin but may be increased for basic drugs such as pseudoephedrine.
Prevention
The risk of a drug-drug interaction depends on the number of drugs used, the tendency of particular drugs to interact, and the amount of drug taken. Many drug-drug interactions are discovered during drug development and testing. They are listed in the prescribing information, in the patient information insert, or on the container for each drug. However, many interactions are not discovered until drugs are used by more people and for longer periods of time. Doctors, nurses, and pharmacists can help reduce the risk of serious problems by keeping informed about potential drug-drug interactions and adjusting drug therapy accordingly. Reference books and computer software programs can help people learn about drug-drug interactions. People can help reduce their risk of interactions by being actively involved in their health care.
People being cared for by several doctors are at highest risk of drug-drug interactions because each doctor may not know all of the drugs being taken. People can reduce this risk by keeping each doctor informed about all drugs being taken and by using one pharmacy to obtain all prescriptions.
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