Predictors of onset and offset of drug effect

Abstract

Anaesthesiologists administer a wide variety of drugs, including benzodiazepines, opioids, intravenous anaesthetic agents, volatile anaesthetic agents, muscle relaxants, local anaesthetics, and other drugs, especially those influencing the cardiovascular system. Sometimes a drug is chosen because of its better effect and/or side-effect profile. However, many of the drugs within each group have similar effect and/or side-effect profiles and differ mainly in their pharmacokinetics. The choice of one drug over another may then need to be based on differences in their pharmacokinetic profiles. Traditional predictors of onset of drug effect, such as time to a specified effect, are dose-dependent. Traditional predictors of offset of drug effect, such as ‘terminal half-life’, often have little clinical relevance. Newer descriptors offer significant advantages. The time to peak effect-site concentration is an informative dose-independent descriptor of the onset of drug effect following an intravenous bolus dose. The relevant decrement time (for continuous measures of drug effect) and mean effect time (for binary measures of drug effect) build upon the context-sensitive half-time concept, by considering the time required for the concentrations to decrease from one clinically relevant level of drug effect to another.