Tachyphylaxis (or desensitisation) described a rapidly decreasing response to a drug following administration of the initial doses. Drug concentrations soon after a single dose cause a greater effect than the same concentrations cause at a later time. This results in a clockwise hysteresis in the dose-response relationship.

As shown in the graphic, the response for a given plasma concentration is initially high, but decreases as tolerance rapidly develops.

Tachyphylaxis can be the consequence of receptor down-regulation, but also of other types of changes in the target tissue.


Well-known examples of tachyphylaxis are the following:

  • Nitroglycerine (nitrates) demonstrates tachyphylaxis, requiring drug-free intervals when administered transdermally to maintain efficacy.
  • Opioids (morphine) also demonstrate tachyphylaxis, but to maintain efficacy clinicians often increase the dose.

Tolerance is defined as a slow decrease in responsiveness to a drug (days/weeks).


Desensitization during prolonged treatment may occur with a number of drugs, eg with benzodiazepines or some anti-epileptics. Which mechanisms may lead to a reduced sensitivity of a receptor after long-term ligand exposure?