Review of Drug Interactions: A Comprehensive Update

Abstract

Prescribing multiple medications predisposes to possibilities of occurrence of drug interactions. Various different terminology and ways exist to classify or arrange drug interactions. Drugs interact with other drugs, foods, beverages and herbs; outside or inside the body. Knowledge of In vitro interactions is essential to avoid loss of activity of drugs before administration. Although every theoretical drug interaction may not manifest in practice, drug interaction is a prominent cause of adverse or undesired events related to drug administration. Amongst the herbs, St. John’s wort has a potential of producing significant drug interactions due to its capacity to induce metabolism of number of drugs. In vivo interactions at pharmacokinetic level affect absorption, distribution, biotransformation or excretion of drugs. Induction or inhibition of cytochrome P450 (CYP450) enzymes forms a major basis of drug interactions. Induction of metabolism of a substrate drug leads to treatment failure. Inhibition of metabolism leads to serious interactions by aggravating toxicity of substrate drugs. As compared to induction, inhibition is a fairly rapid process, and number of precipitant drugs which inhibit the metabolism is much more than that of inducers. Role of drug transporters, especially P-glycoprotein (P-gp), in causation of drug interactions is being increasingly identified. P-gp affects absorption, distribution and excretion, and hence plays a major role in pharmacokinetic drug interactions. Additionally, P-gp works hand in hand with CYP450 enzymes. In pharmacodynamic interactions, the drugs synergise or antagonise the effect at the level of target of action. Clinically beneficial and reparative drug interactions are explored to obtain useful drug combinations. Extensive research has led to development of a large number of In vitro and In vivo methods to detect and predict drug interactions. Appropriate awareness and knowledge of possible drug interactions is crucial in prevention of drug interactions and their consequences.