The doughnut and the hole: a new pharmacological concept for anaesthetists

Abstract

It is time for anaesthetists to revisit a long acknowledged but little considered concept in clinical pharmacology. In our daily practice, we regularly think about the law of mass action, about reversible reactions and about diffusion gradients. We accept that passive diffusion along concentration gradients is a common cause of the pharmacological effects we utilize in every anaesthetic. Thus it is easy to conceive of recovery from neuromuscular block induced by the depolarizing agent, succinylcholine, occurring as the concentration of the drug reduces in the plasma following metabolism by plasma cholinesterase. The drug moves passively from the higher concentration at the postsynaptic nicotinic receptor back in to the plasma and recovery occurs. We also accept that if a further bolus dose of such a drug is given, neuromuscular block recurs: the balance of concentration of the drug would be shifted in the opposite direction.