True about tachyphylaxis: (PGI Dec 2006)

Ans: D (Indirect sympthomimetics involved) [Ref.KDT6th / 68; Goodman Gilman's 11th /31,162,170)Tachyphylaxis (Tachy-fast; Phylaxis-Protection)# It is the rapid development of tolerance when doses of a durg repeated in quick succession result in marked reduction in response.Tachyphalaxis is usually seen with indirectly acting drugsfi e.g. indirect acting sympathomimetics tyramine, ephedrine, amphetamine, nicotine etc.Mechanism of tachyphylaxis is incompletely understood but following suggestion have got importances:i. Temporary inaccessibility of receptor to agonists,ii. Fewer receptors synthesized and available on cell surface.iii. Agonists stimulation of GPCRs initiates regulatory process that are rapid, leading to tachyphylaxis or densitization. It is said that phosphorylation of GPCR (G protein coupled recepotrs) kinases plays a key role in triggering densensitization