What are drug interactions?

Interactions and Drug Metabolism

Medications and recreational drugs are metabolized in the body into pharmacologically active chemical components; nonpharmacologically active chemical moieties are then excreted from the body. Most medications are either metabolized by the kidney (renal metabolism) or by the liver (hepatic metabolism).

Within the liver and intestines exist multiple enzymes and pathways responsible for breaking down medications. Some of the enzymes that are most commonly involved in drug metabolism are the cytochrome P450 (CYP) enzymes. Of the CYP enzymes, CYP3A4 is most commonly involved in drug metabolism. It has been estimated that this enzyme is at least partly responsible for the metabolism of almost 50 percent of medications. The rate and amount of drug that can be metabolized depends on a number of factors, including the amount of enzyme present and the speed at which these enzymes are working.

When a person ingests multiple medications metabolized through the same pathway, the enzymes may not be able to metabolize all the medications simultaneously, leading to elevated, possibly toxic, levels of the drugs. For example, alprazolam (Xanax) is metabolized through CYP3A4. If a patient taking alprazolam is prescribed clarithromycin (Biaxin) for sinusitis and takes the two medications together, the clarithromycin, a CYP3A4 inhibitor, will effectively slow the breakdown of alprazolam, leading to increased sedation and central nervous system (CNS) depression. If the patient continues to take alprazolam, unaware that drug levels are building up in his or her system, dangerous consequences can occur.

Drug-Food Interactions

In addition to the medications that may interact with one another, drugs also can have interactions with food. Milk and other calcium- and magnesium-containing products can interact with certain medications, including fluoroquinolone antibiotics such as ciprofloxacin (Cipro) and levofloxacin (Levaquin). Divalent cations such as calcium and magnesium can bind the antibiotic, keeping it from being absorbed by the body. Citrus juices, especially grapefruit juice, are also known to strongly interact with various drugs.

Another example of drug and food interactions is the heightened CNS depressant effects of alcohol when combined with medications that already produce CNS depressant effects, such as benzodiazepines (alprazolam, or Xanax, and lorazepam, or Ativan) and morphine or morphine derivatives (such as the hydrocodone products Vicodin, Norco, and Loratab and the oxycodone products Percocet and Percodan).

CNS depressant medications and substances, such as alcohol, slow down certain brain processes. This can lead to decreased motor function and coordination, drowsiness, confusion, and respiratory depression. CNS effects are cumulative, which is why the addition of alcohol to the system of a person taking either chronic or recreational (and legal) CNS depressants can be so dangerous. These medications and the resulting sensations can have addictive properties, leading the user to purposely combine the two in an unsafe and potentially fatal manner.

Drug and Herbal Supplements Interactions

Herbal medications are often assumed to be more natural and, therefore, safer than pharmacologically produced medications. The use of these agents has continued to increase, although the exact number of people using supplements is hard to gauge because these agents are available without a prescription (over the counter).

Some of the most popular supplements have serious interactions with common medications. These supplements include St. John’s wort, Ginkgo biloba, ginseng, and garlic. St. John’s wort, which is used to treat many ailments, most commonly depression, is metabolized through CYP 3A4 and 2E1 and, therefore, can be unsafe when used with some anticoagulants, including warfarin, and with some medications used to treat human immunodeficiency virus (including protease inhibitors and non-nucleoside reverse transcriptase inhibitors). Ginkgo is commonly used for memory enhancement. There have been numerous reports of bleeding in patients taking ginkgo while also taking anticoagulants, and in patients with clotting disorders.

It is important that patients understand that herbal supplements, although generally safe, can dangerously interact with over-the-counter and prescription medications. Patients should alert their doctors, pharmacists, and other providers about what supplements they are taking to help prevent serious interactions.

Bibliography

"Drug Interactions: What You Should Know." FDA. US Food and Drug Administration, 25 Sept. 2013. Web. 27 Oct. 2015.

Izzo, Angelo, and Edzard Ernst. “Interactions between Herbal Medicines and Prescribed Drugs.” Drugs 61.15 (2001): 2163–75. Print.

"Medication Interaction: Food, Supplements, and Other Drugs." American Heart Association. American Heart Assn., 15 Oct. 2014. Web. 27 Oct. 2015.

Saito, Mitsuo, et al. “Undesirable Effects of Citrus Juice on the Pharmacokinetics of Drugs.” Drug Safety 28.8 (2005): 677–94. Print.

Wallace, Allison W., Jennifer M. Victory, and Guy W. Amsden. “Lack of Bioequivalence When Levofloxacin and Calcium-Fortified Orange Juice Are Coadministered to Healthy Volunteers.” Journal of Clinical Pharmacology 43 (2003): 539–44. Print.