Clinically significant interactions with anesthetic agents

Induction and maintenance of anesthesia require multiple medications where drug-drug interactions form the basis of clinical practice. Drug-drug interactions with anesthetic agents can take place by pharmacokinetic mechanisms leading to enhanced or reduced pharmacodynamic effects or by only pharmacodynamic mechanism that promotes anesthetic outcomes such as pain and sedative actions. Ketamine, midazolam, and alfentanil are metabolized by the CYP3A4 enzyme system and various drug-drug interactions with agents that are well-known CYP3A4 inhibitors have been reported to alter their pharmacokinetic disposition. Antibiotics erythromycin and clarithromycin were found to significantly reduce ketamine and midazolam disposition. Grapefruit juice was reported to significantly increase ketamine and midazolam bioavailability. Antifungal drugs such as ketoconazole and fluconazole were shown to significantly reduce alfentanil clearance and prolong its pharmacodynamic actions. Drug interactions with opioid anesthetics fentanyl and sufentanil may be less prone to due to their high extraction ratio. The opioidpropofol interactions have been described in various articles. Propofol interactions were also presented with midazolam and interestingly counteracted the effects of droperidol-induced prolonged QTc effects. Thiopental protein-binding displacement was shown to occur with a variety of agents, thereby increasing free drug concentrations. An enhanced pharmacodynamic effect with thiopental was found when combined with midazolam and other central nervous system depressants.