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).
Generally speaking, drug interactions are best avoided, due to the possibility of poor or unexpected outcomes. However, in some instances, drug interactions have been deliberately used to great effect, such as the co-administration of 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 of penicillin required for a course of therapy. Since probenecid reduces the excretion of penicillin from the body, a dose of penicillin will stay around the body for a longer period of time when taken with probenecid. Hence, probenecid allows individuals to take less penicillin over a course of therapy. In the present day, probenecid is generally no longer used for this purpose, since penicillin is now produced on a large-scale basis.
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. 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.
- Drug Interactions: What You Should Know. U.S. Food and Drug Administration, Center for Drug Evaluation and Research
- The Medical Letter's Adverse Drug Interactions Database
- Cytochome P450 table maintained by the Indiana University School of Medicine
- Free Drug Interaction Checker