Drug interactions result from a number of underlying pharmacokinetic and pharmacodynamic mechanisms
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DRUG REACTIONS AND INTERACTIONS
Drug interactions result from a number of underlying pharmacokinetic and pharmacodynamic mechanisms Adis Medical Writers
Published online: 17 May 2013 Springer International Publishing Switzerland 2013
Abstract In order to predict and prevent drug interactions in clinical practice, it is essential that healthcare professionals have a good knowledge of the main mechanisms underlying drug–drug and drug–food interactions. Although many theoretical interactions are not clinically significant, the potential for clinically relevant drug interactions is increasing as the population ages, the use of polypharmacy becomes even more common and new drugs are developed.
polypharmacy and multi-morbidity are associated with higher rates of hospital admissions due to adverse drug interactions [1, 4, 5]. Although some interactions may occur prior to drug administration (e.g. when drugs are mixed inappropriately in syringes or infusion fluids before administration [6]), most interactions occur after administration [1]. This articles summarizes the principal pharmacokinetic and pharmacodynamic mechanisms involved in drug–drug and drug–food interactions, as reviewed by Brewer and Williams [1].
Risk of interactions is increasing
Pharmacokinetic interactions change drug exposure
Drug–drug and drug–food interactions represent a significant risk in the prescribing of medications [1]. Although many theoretical drug interactions are not clinically relevant, the potential number of interactions increases as more drugs are introduced to the market. The effects (both desired and undesired) of a drug are related to the concentration at its sites of action. The level of drug exposure is affected by the drug’s pharmacokinetics (absorption, distribution, enzyme metabolism, protein transport and/or excretion), which can be influenced by concomitantly administered food or drugs [2]. The pharmacodynamic effect of a drug may also be altered if coprescribed with another drug or food substance that acts on the same receptor or physiological system [3]. Older age,
Pharmacokinetic interactions, which result in a change in exposure to the active drug, account for the majority of commonly encountered drug interactions [1]. These interactions can involve changes in drug absorption, distribution and hepatic metabolism, expression or activity of drug transporter proteins, and/or drug elimination (Table 1). The principal mechanism underlying most clinically relevant pharmacokinetic drug interactions is impairment of drug elimination due to interference with hepatic metabolism, renal excretion or transcellular transport [1]. Cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 isoenzymes play a major role in drug metabolism, with CYP3A4 being responsible for metabolizing the greatest number of drugs [7, 8]. Potential drug-drug interactions involving these enzymes (Table 1) result from relatively specific CYP isoenzyme induction or inhibition [9]. Table 2 lists examples of common substrates, inducers and inhibitors
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