Whenever two or more drugs are taken concurrently, there is a chance that there will be an interaction among the drugs. The interaction may increase or decrease the effectiveness and/or the side effects of the drugs. It also may result in a new side effect, that is, a side effect not seen with the use of any one drug alone. The likelihood of drug interactions increases as the number of drugs being taken by a patient increases.

Therefore, people who take several medications are at the greatest risk for interactions. Drug interactions contribute to the cost of healthcare because of the medical care costs that are required to treat them. Interactions can also lead to pain and suffering that could be avoided. This month’s topic 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 in the body; (3) changes 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. 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 an alteration in blood flow to the intestine, metabolism (alteration of the drug) by the intestine, increased or decreased intestinal motility (movement) within the intestine, alterations in acidity in the stomach, and a change in the bacteria of 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 (e.g., 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 metabolism (alteration) 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 easier for the body to eliminate through the kidneys. (This process also converts drugs that are given in inactive forms into active forms that actually produce the desired effect.) Most drug metabolism takes place in the liver, but other organs also may play a role (e.g., the kidneys). 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.

What are the consequences of drug interactions?

Drug interactions may lead to an increase or decrease in the beneficial or the adverse effects of the given drugs. When a drug interaction increases the benefit of the administered drugs without increasing side effects, both drugs may be combined to increase the control of the condition that is being treated. For example, drugs that reduce blood pressure by different mechanisms may be combined because the blood pressure lowering effect achieved by both drugs may be better than with either drug alone. The absorption of some drugs is increased by food. Therefore, these drugs are taken with food in order to increase their concentration in the body and, ultimately, their effect. Conversely, when a drug’s absorption is reduced by food, the drug is taken on an empty stomach.

Drug interactions that are of greatest concern are those that reduce the desired effects or increase the adverse effects of the drugs. Drugs that reduce the absorption or increase the metabolism or elimination of other drugs tend to reduce the effects of the other drugs. This may lead to failure of therapy or warrant an increase in the dose of the affected drug. Conversely, drugs that increase absorption or reduce the elimination or metabolism of other drugs increase the concentration of the other drugs in the body and lead to more side effects. Sometimes, drugs interact because they produce similar side effects. Thus, when two drugs that produce similar side effects are combined, the frequency and severity of the side effect are increased.

How often do drug interactions occur?

Drug interactions are complex and chiefly unpredictable. A known interaction may not occur in every individual. This can be explained because there are several factors that affect the likelihood that a known interaction will occur. These factors include differences among individuals in physiology, age, lifestyle (diet, exercise), underlying diseases, drug doses, the duration of combined therapy, and the relative time of administration of the two substances. (Sometimes, interactions can be avoided if two drugs are taken at different times.) Nevertheless, significant drug interactions occur frequently and they add millions of dollars to the cost of healthcare. Moreover, many drugs have been withdrawn from the market because of their potential to interact with other drugs and cause serious healthcare problems.

How can drug interactions be avoided?

 
1. Give healthcare providers a complete list of all of the drugs that you are using or have used within the last few weeks. This should include over-the-counter medications, vitamins, food supplements, and herbal remedies.  
2. Inform healthcare providers when medications are added or discontinued.  
3. Inform healthcare providers about changes in lifestyle.  
4. Ask your healthcare provider about the most serious or frequent drug interactions with the medications that you are taking.  
5. Since the frequency of drug interactions increases with the number of medications, work with your healthcare providers to eliminate unnecessary medications.  
6. Use the MedicineNet drug interaction tool to screen for possible drug interactions. However, always consult your healthcare provider before you make any adjustments to your therapy.  
7. This brief overview of drug interactions does not cover every possible scenario. Viewers should not be afraid to use their drugs because of the potential for drug interactions. Rather, they should use the information that is available to them to minimize the risk of such interactions and to improve the success of their therapy.