Potentially hazardous drug interactions with psychotropics

Of the many interactions with psychotropic drugs, a minority are potentially hazardous. Most interactions are pharmacodynamic, resulting from augmented or antagonistic actions at a receptor or from different mechanisms in the same tissue. Most important pharmacokinetic interactions are due to effects on metabolism or renal excretion. The major enzymes involved in metabolism belong to the cytochrome P450 (CYP) system. Genetic variation in the CYP system produces people who are ‘poor’, ‘extensive’ or ‘ultra-rapid’ drug metabolisers. Hazardous interactions more often result from enzyme inhibition, but the probability of interaction depends on the initial level of enzyme activity and the availability of alternative metabolic routes for elimination of the drug. There is currently interest in interactions involving uridine diphosphate glucuronosyltransferases and the P-glycoprotein cell transport system, but their importance for psychotropics has yet to be defined. The most serious interactions with psychotropics result in profound sedation, central nervous system toxicity, large changes in blood pressure, ventricular arrhythmias, an increased risk of dangerous side-effects or a decreased therapeutic effect of one of the interacting drugs. Potentially hazardous drug interactions with psychotropics 441 Advances in Psychiatric Treatment (2005), vol. 11. http://apt.rcpsych.org/ before intravenous infusion can result in precipitation or inactivation. An example is the incompatibility of phenobarbital with chlorpromazine or opioid analgesics when mixed in the same syringe. Of the three mechanisms, pharmaceutical interactions are least likely to cause problems in clinical practice, and there are no potentially hazardous interactions of this type with psychotropic drugs. Pharmacodynamic interactions The most common interactions encountered in clinical practice are pharmacodynamic. They occur when drugs compete for the same receptor or produce antagonistic or synergistic effects on the same target organ or system. Many instances of antagonism are beneficial: for example, naloxone is a specific Table 1 Types and examples of drug interactions Interaction type Example