Desensitisation and tachyphylaxis

Desensitization refers to the common situation where the biological response to a drug diminishes when it is given continuously or repeatedly. It may be possible to restore the response by increasing the dose (or concentration) of the drug but, in some cases, the tissues may become completely refractory to its effect. The term tachyphylaxis is used to describe desensitization that occurs very rapidly, sometimes with the initial dose. The term tolerance is conventionally used to describe a more gradual loss of response to a drug that occurs over days or weeks. There is no clear distinction but the different scales imply that different mechanisms may be involved. Rapid development implies the depletion of chemicals that may be necessary for the pharmacological actions of the drug (e.g. a stored neurotransmitter released from a nerve terminal) or receptor phosphorylation. Slower development implies changes in receptor numbers or the development of counter-­‐regulatory physiological changes that offset the actions of the drug (e.g. accumulation of salt and water in response to vasodilator therapy) or reduction of target receptor numbers. The term refractoriness is often used to describe a state where there is lack of responsiveness to a drug. Drug resistance is a term normally reserved to describe the loss of effectiveness of an antimicrobial or cancer chemotherapy drug. In addition to these pharmacodynamic causes of diminished effectiveness, reduced response may be the consequence of a reduction in the plasma and tissue drug concentrations that result from the same drug dose, because of alterations in the way the drug is handled (its ‘pharmacokinetics’). Where desensitization to a drug arises because of established chemical, hormonal and physiological changes that offset the actions of the drug, discontinuation may mean that these changes themselves cause ‘rebound’ withdrawal effects (e.g. nitrates, opioids, benzodiazepines).

Professor Simon Maxwell