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Drug Interactions: Prescription Drugs & OTC Medications

What facts should I know about drug interactions?

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 their side effects. The likelihood of drug interactions increases as the number of drugs being taken increases. Therefore, people who take many 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. 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, such as supplements. Drugs also may interact with laboratory tests, changing the proper results of the laboratory test.

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);
  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 can cause sedation are taken simultaneously, such as narcotics with 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 effectiveness 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 ways that 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 normally 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


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Change in drug metabolism and elimination

Most drugs are eliminated through the kidney in either an unchanged form or
metabolized 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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How often do drug interactions occur?

The prescribing information for most drugs contains a list of potential drug
interactions. Many of the listed interactions may be rare, minor, or only occur
under specific conditions and may not be important. Drug interactions that cause
important changes in the action of a drug are of greatest concern.

interactions are complex and often 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 their:

  • genes,
  • physiology,
  • age,
  • lifestyle (diet, exercise),
  • hydration,
  • 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

Nevertheless, important drug interactions occur frequently and they add
millions of dollars to the cost of health care. Moreover, many drugs have been
withdrawn from the market because of their potential to interact with other
drugs and cause serious health care problems.

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 increased
amounts of drug in the body and 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.

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How can drug interactions be avoided?

  1. Give healthcare professionals 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 professionals when medications are added or discontinued.
  3. Inform healthcare professionals about changes in lifestyle (for example, exercise,
    diet, alcohol intake.
  4. Ask your healthcare professionals 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 professionals to eliminate unnecessary medications.
    Always discuss potential drug interactions with our pharmacist.

This brief overview of drug interactions does not cover every possible
scenario. Individuals 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.


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