Drug interaction

A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interaction between drugs come to mind (drug-drug interaction). However, interactions may also exist between drugs & foods (drug-food interactions), as well as drugs & herbs (drug-herb interactions). These may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances.^[1]

Generally speaking, drug interactions are to be avoided, due to the possibility of poor or unexpected outcomes. However, drug interactions have been deliberately used, such as co-administering probenecid with penicillin prior to mass production of penicillin. Because penicillin was difficult to manufacture, it was worthwhile to find a way to reduce the amount required. Probenecid retards the excretion of penicillin, so a dose of penicillin persists longer when taken with it, and it allowed patients to take less penicillin over a course of therapy.

A contemporary example of a drug interaction used as an advantage is the co-administration of carbidopa with levodopa (available as Carbidopa/levodopa). Levodopa is used in the management of Parkinson's disease and must reach the brain in an un-metabolized state to be beneficial. When given by itself, levodopa is metabolized in the peripheral tissues outside the brain, which decreases the effectiveness of the drug and increases the risk of adverse effects. However, since carbidopa inhibits the peripheral metabolism of levodopa, the co-administration of carbidopa with levodopa allows more levodopa to reach the brain un-metabolized and also reduces the risk of side effects.

Drug interactions may be the result of various processes. These processes may include alterations in the pharmacokinetics of the drug, such as alterations in the Absorption, Distribution, Metabolism, and Excretion (ADME) of a drug. Alternatively, drug interactions may be the result of the pharmacodynamic properties of the drug, e.g. the co-administration of a receptor antagonist and an agonist for the same receptor.

Metabolic drug interactions

Many drug interactions are due to alterations in drug metabolism.^[2] Further, human drug-metabolizing enzymes are typically activated through engagement of nuclear receptors.^[2]

One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidases. This system may be affected by either enzyme induction or enzyme inhibition, as discussed in the examples below.

• Enzyme induction - drug A induces the body to produce more of an enzyme which metabolises drug B. This reduces the effective concentration of drug B, which may lead to loss of effectiveness of drug B. Drug A effectiveness is not altered.
• Enzyme inhibition - drug A inhibits the production of the enzyme metabolising drug B, thus an elevation of drug B occurs possibly leading to an overdose.
• Bioavailability - drug A influences the absorption of drug B.

The examples described above may have different outcomes depending on the nature of the drugs. For example, if Drug B is a prodrug, then enzyme activation is required for the drug to reach its active form. Hence, enzyme induction by Drug A would increase the effectiveness of the drug B by increasing its metabolism to its active form. Enzyme inhibition by Drug A would decrease the effectiveness of Drug B.

Additionally, Drug A and Drug B may affect each other's metabolism.

Epidemiology

Among US adults older than 55, 4% are taking medication and or supplements that put them at risk of a major drug interaction.^[3]

See also

• Classification of Pharmaco-Therapeutic Referrals
• List of drug interactions

References

1. ^ " National Prescribing Service, 2009. Available at http://nps.org.au/news_and_media/media_releases/repository/Forget_the_colour_shape_or_brand__its
2. ^ ^{a b} Elizabeth Lipp (2008-06-15). "Tackling Drug-Interaction Issues Early On". Genetic Engineering & Biotechnology News (Mary Ann Liebert, Inc.): pp. 14, 16, 18, 20. http://www.genengnews.com/articles/chitem.aspx?aid=2509. Retrieved 2008-07-06. "(subtitle) Researchers explore a number of strategies to better predict drug responses in the clinic" 
3. ^ "JAMA -- Abstract: Use of Prescription and Over-the-counter Medications and Dietary Supplements Among Older Adults in the United States, December 24/31, 2008, Qato et al. 300 (24): 2867". http://jama.ama-assn.org/cgi/content/short/300/24/2867. 

External links

• Drug Interactions: What You Should Know. U.S. Food and Drug Administration, Center for Drug Evaluation and Research
• Medfacts Pocket guide for Drug Interaction Published by Nephrology pharmacy associates NPA Second Edition
• Cytochome P450 table maintained by the Indiana University School of Medicine
• Free Drug Interaction Checker