Drug Interactions

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Drug interactions overview

Whenever two or more drugs are being taken, there is a chance that there will be an interaction among the drugs. The interaction may increase or decrease the effectiveness of the drugs or the side effects of the drugs. The likelihood of drug interactions increases as the number of drugs being taken increases. Therefore, people who take several drugs are at the greatest risk for interactions. Drug interactions contribute to the cost of healthcare because of the costs of medical care that are required to treat problems caused by changes in effectiveness or side effects. Interactions also can lead to psychological suffering that can be avoided. This review discusses the issue of drug interactions and several ways to avoid them.

What are drug interactions?

A drug interaction can be defined as an interaction between a drug and another substance that prevents the drug from performing as expected. This definition applies to interactions of drugs with other drugs (drug-drug interactions), as well as drugs with food (drug-food interactions) and other substances.

How do drug interactions occur?

There are several mechanisms by which drugs interact with other drugs, food, and other substances. An interaction can result when there is an increase or decrease in:

  1. the absorption of a drug into the body;

  2. distribution of the drug within the body;

  3. alterations made to the drug by the body (metabolism); and

  4. elimination of the drug from the body.

Most of the important drug interactions result from a change in the absorption, metabolism, or elimination of a drug. Drug interactions also may occur when two drugs that have similar (additive) effects or opposite (canceling) effects on the body are administered together. For example, there may be major sedation when two drugs that have sedation as side effects are given, for example, narcotics and antihistamines. Another source of drug interactions occurs when one drug alters the concentration of a substance that is normally present in the body. The alteration of this substance reduces or enhances the effect of another drug that is being taken. The drug interaction between warfarin (Coumadin) and vitamin K-containing products is a good example of this type of interaction. Warfarin acts by reducing the concentration of the active form of vitamin K in the body. Therefore, when vitamin K is taken, it reduces the effect of warfarin.

Change in absorption

Most drugs are absorbed into the blood and then travel to their site of action. Most drug interactions that are due to altered absorption occur in the intestine. There are various potential mechanisms through which the absorption of drugs can be reduced. These mechanisms include:

  1. an alteration in blood flow to the intestine;

  2. change in drug metabolism (breakdown) by the intestine;

  3. increased or decreased intestinal motility (movement);

  4. alterations in stomach acidity, and

  5. a change in the bacteria that reside in the intestine.

Drug absorption also can be affected if the drug's ability to dissolve (solubility) is changed by another drug or if a substance (for example, food) binds to the drug and prevents its absorption.

Change in drug metabolism and elimination

Most drugs are eliminated through the kidney in either an unchanged form or as a by-product that results from the alteration (metabolism) of the drug by the liver. Therefore, the kidney and the liver are very important sites of potential drug interactions. Some drugs are able to reduce or increase the metabolism of other drugs by the liver or their elimination by the kidney.

Metabolism of drugs is the process through which the body converts (alters or modifies) drugs into forms that are more or less active (for example, by converting drugs that are given in inactive forms into their active forms that actually produce the desired effect) or that are easier for the body to eliminate through the kidneys. Most drug metabolism takes place in the liver, but other organs also may play a role (for example, the kidneys, intestine, etc.). The cytochrome P450 enzymes are a group of enzymes in the liver that are responsible for the metabolism of most drugs. They are, therefore, often involved in drug interactions. Drugs and certain types of food may increase or decrease the activity of these enzymes and therefore affect the concentration of drugs that are metabolized by these enzymes. An increase in the activity of these enzymes leads to a decrease in the concentration and effect of an administered drug. Conversely, a decrease in enzyme activity leads to an increase in drug concentration and effect.




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