Tachyphylaksia

Tachyphylaksia, also spelled tachyphylaxis, is a pharmacological phenomenon characterized by a rapid decline in responsiveness to a drug after repeated or continuous exposure. The decrease in effect can occur within minutes to hours and may require higher doses, alternative therapies, or drug-free intervals to restore responsiveness. Tachyphylaksia is distinct from tolerance, which develops more slowly and may persist longer after drug withdrawal.

The mechanisms are primarily pharmacodynamic. Receptor desensitization often involves receptor phosphorylation by G-protein-coupled receptor kinases, recruitment of beta-arrestins, and receptor internalization, diminishing signaling despite ongoing drug presence. Other mechanisms include depletion of mediators (for example, neurotransmitters or mediators released by cells), changes in downstream second messenger systems, or adaptive changes in ion channels and cellular excitability. In some cases tachyphylaksia results from functional depletion of a mediator rather than receptor changes.

Tachyphylaksia is reported with several drug classes, notably nitrate vasodilators (such as nitroglycerin) and certain decongestants and vasopressors that act through alpha-adrenergic pathways. It has also been observed with other rapid-acting agents used topically or systemically. The clinical significance depends on the therapeutic context, requiring monitoring and, if needed, drug scheduling strategies to minimize loss of effect.

Etymology and history: The term derives from Greek tachys ‘swift’ and phylaxis ‘guard’ and was introduced to describe rapid loss of drug response. In pharmacology, tachyphylaksia is an established concept alongside tolerance and dependence, and continues to be a focus of research on receptor signaling and adaptive responses.