TRC: Tachyphylaxis

Tachyphylaxis

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?

Extra info: Strong ligand binding or prolonged stimulation of receptors may cause some types of receptors to dissociate from post-receptor processes, to ‘fall apart’ in subunits, to be ‘withdrawn’ from the cell surface and/or to be recycled less rapidly.

Option explanation:

Decrease in receptor degradation and increase in receptor recycling

Decrease in receptor sensitivity and increase in receptor expression

Increase in receptor degradation and decrease in receptor recycling

Increase in receptor sensitivity and decrease in receptor expression

Tachyphylaxis

Tachyphylaxis

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