Local anaesthetics: Theoretical aspects

Local anaesthetics are frequently used in both primary and secondary care. These agents transiently reduce the nervous conduction of nociceptive signals, reducing sensations of pain. In primary care, local anaesthetics are often used for minor surgical procedures. However, there are other uses for these agents. It is important to understand the issues encountered when using local anaesthetics in primary care. This review will cover clinical use, relevant pharmacology and adverse effects of the different local anaesthetic preparations.

Temperature and reaction rate

All other things being equal, physiological reaction rate increases roughly exponentially with temperature. Organisms that have adapted over evolutionary time to live at different temperatures can have enzyme variants that exhibit similar kinetics at the temperatures to which they have adapted to operate. Within species whose distribution covers a range of temperatures, there may be differential expression of enzyme variants with different kinetics across the distribution. Enzymes adapted to different optimum temperatures differ in their amino acid sequence and thermal stability. The Gibbs energy of activation tends to be slightly lower in enzyme variants adapted to lower temperatures, but the big change is a decrease in the enthalpy of activation, with a corresponding change in the entropy of activation, both associated with a more open, flexible structure. Despite evolutionary adjustments to individual enzymes involved in intermediary metabolism (ATP regeneration), many whole-organism processes operate faster in tropical ectotherms compared with temperate or polar ectotherms. Examples include locomotion (muscle power output), ATP regeneration (mitochondrial function), nervous conduction and growth.