- Tachyphylaxis is an acute decrease in response to repeated doses over a short time period
- The most common mechanism is the depletion of (neuro)transmitter stores before resynthesis can take place
- Drugs exhibiting tachyphylaxis:
- Ephedrine, an indirectly acting sympathomimetic amine owing to depletion of noradrenaline stores
- GTN
- Trimetaphan (a non-competitive nicotinic ACh receptor antagonist)
Tachyphylaxis, Desensitisation and Tolerance
Tachyphylaxis, Desensitisation and Tolerance
- Repeated doses of a drug may lead to a change in pharmacological response for the same dose (increase or decrease in response)
- Desensitisation is a chronic loss of response over a longer period
- Mechanisms include:
- Structural change in receptor morphology
- Absolute loss of receptor numbers
- Changes in downstream signalling pathways
- For example, the loss of β-adrenoreceptors from myocardial cell surfaces in the continued presence of adrenaline and dobutamine
- Tolerance is the phenomenon whereby larger doses of a substance are required to produce the same pharmacological effect
- Mechanisms include:
- Reduction of receptor density
- Reduction of receptor affinity
- Examples include:
- Chronic opioid use/abuse
- Nitrate infusion - vascular smooth muscle sulfhydryl groups become depleted
- This can be circumvented by a 'drug holiday' overnight to allow replenishment of the sulfhydryl groups