Clinically significant interactions with benzodiazepines

Benzodiazepines are a class of lipophilic compounds used for a variety of indications including anxiety disorders, insomnia, epilepsy, musculoskeletal disorders, and as sedatives during surgery. The chemical nucleus of each benzodiazepine as well as their pharmacodynamic activity is identical. However, alterations to this basic structure lead to numerous benzodiazepines with different pharmacokinetic properties and lipid solubility resulting in agents with differing rates of elimination, concentrations, volumes of distribution, and potencies. In this chapter we will review the varied kinetics of available benzodiazepines and discuss the metabolic pathways leading to excretion of these medications. This review includes the enzymes (Phase I and Phase II) responsible for metabolism of the parent compound and their intermediates. We also review the pharmacologic and pharmacokinetic activity of the intermediate metabolites. Furthermore we will identify pharmacokinetic interactions of benzodiazepines including: drug-drug interactions, P-gylcoprotein interactions, protein-binding interactions, and food/herbal interactions. Other factors that may require alterations in benzodiazepine dosing such as weight, sex, age, smoking status, genetic polymorphisms, and pharmacokinetic interactions will similarly be discussed. Finally we will identify the clinical monitoring that is required for individuals being prescribed benzodiazepines including respiratory depression, sedation, and withdrawal. The goal of this chapter is to give the reader a background of the factors that should be considered when choosing or monitoring the available benzodiazepines in clinical practice.