4 The role of the cytochrome P450 system in drug interactions in anaesthesia

The cytochrome P450 enzyme system is involved in the metabolism of many drugs used in anaesthesia, including benzodiazepines, opioids and most volatile anaesthetic agents. Most intravenous anaesthetic drugs are metabolized by the specific isoform, CYP3A, while the volatile agents are metabolized by CYP2E1. Many substances are inducers or inhibitors of cytochrome P450, including several commonly used drugs, and these may interact with anaesthetic drugs, giving rise to unpredictable pharmacokinetic and pharmacodynamic changes. Enzyme inhibition will result in reduced drug metabolism, with higher than expected blood concentrations and thus greater and more prolonged clinical effects. These can manifest as prolonged awakening times, and particularly with the opioids, prolonged and potentially life-threatening respiratory depression. In contrast, enzyme induction will result in lower than expected plasma concentrations and a reduction in pharmacological effect. This could increase the risk of intra-operative awareness and diminished analgesia after surgery. This article reviews the current knowledge with respect to drug interactions involving the cytochrome P450 enzyme system and drugs used in anaesthesia.