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Tachyphylaxis is a medical term describing 'A rapid decrease in the response to a drug after repeated doses over a short period of time'. Increasing the dose of the drug will not increase the pharmacological response. Tachyphylaxis may develop with an initial dose. The cause of this phenomenon is depletion of the neurotransmitter that is involved in the action of the drug. The drug causing tachyphylaxis acts indirectly by causing release of the stored neurotransmitter from the nerve terminal. After a few doses the neurotransmitter stores are depleted and no more response is obtained.

Examples: Amphetamine, ephedrine (indirectly acting drugs)

Tachyphylaxis is a phenomenon which is characterized by the rate sensitivity: the response of the system depends on the rate with which a stimulus is presented. Specifically, a high intensity prolonged stimulus or often repeated stimulus may bring about a diminished response also known as desensitization.

In biological sciences, molecular interactions are the physical bases of the operation of the system. The control of the operation, generally, involves interaction of a stimulus molecule with a receptor / enzyme subsystem by, typically, binding to the macromolecule A and causing an activation or an inhibition of the subsystem by forming an activated form of the macromolecule B. Schematically,

          p    A --------> B 

Where p is the activation rate coefficient. Customarily, p is called a rate constant, but, since the p stands for measure of the intensity of the stimulus causing the activation, p may be variable (non-constant).

The above scheme is only the necessary condition for the rate sensitivity phenomenon and other pathways of deactivation of B may be considered, with the subsequent return to the inactive form of the receptor/enzyme A. Examples^[1][2][3] offer particular use of such (mathematical) models in endocrinology, physiology and pharmacology.

Contents 1 Examples 2 References 3 See also 4 External links

[edit] Examples

Examples of tachyphylaxes are the following:

• Nitroglycerine demonstrates tachyphylaxis, requiring drug-free intervals when administered transdermally
• Repeated doses of ephedrine may display tachyphylaxis, since it is an indirectly acting sympathomimetic amine which will deplete noradrenaline from the nerve terminal. Thus repeated doses result in less noradrenaline being released than the initial dose.
• Nicotine may also show tachyphylaxis over the course of a day, although the mechanism of this action is unclear.
• Hydralazine displays tachyphylaxis if given as a monotherapy for antihypertensive treatment. It is administered with a beta-blocker with or without a diuretic.
• Metoclopramide is another example.
• Dobutamine, a direct-acting beta agonist used in congestive heart failure, also demonstrate tachyphylaxis.
• Desmopressin used in the treatment of type 1 von Willebrand disease is generally given every 12-24 hours in limited numbers due to its tachyphylactic properties.
• Hormone replacement when used in menopausal women in the form of oestrogen and progesterone implants is cited as potentially leading to tachyphylaxis, but that citation is based on a single study done in 1990^[4] and no followup research is available to support this interpretation.
• Psychedelics such as LSD-25 and psilocybin containing mushrooms demonstrate very rapid tachyphylaxis. In other words, one may be unable to 'trip' two days in a row. Some people are able to 'trip' by taking up to three times the dosage, some users may not be able to negate tachyphylaxis at all until a period of days has gone by.^{[citation needed]}
• In a patient fully withdrawn from centrally-acting analgesics, viz. opioids, going back to an intermittent schedule or maintenance dosing protocol, a fraction of the old tolerance level will rapidly develop, usually starting two days after opioid therapy is resumed and generally levelling off after day 7. Whether this is caused directly by opioid receptors modifed in the past or effecting a change in some metabolic set-point is unclear. Increasing the dose will usually restore efficacy; relatively rapid opioid rotation may also be of use if the increase in tolerance continues.

[edit] References

[edit] See also

• Desensitization (medicine)
• Physiological tolerance
• Physical dependence
• Mithridatism

See Lehne, R. 2007, PHARMACOLOGY FOR NURSING CARE, Saunders/Elsevier, St. Louis, p.79 for more info.

[edit] External links

• MeSH Tachyphylaxis

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