Tachyphylaxis - AbsoluteAstronomy.com

Tachyphylaxis is a medical term describing a decrease in the response to a drug due to previous exposure to that drug. Increasing the dose of the drug may be able to restore the original response. In this context tachyphylaxis is a synonym for drug tolerance. This can sometimes be caused by depletion or marked reduction of the amount of neurotransmitter responsible for creating the drug's effect, or by the depletion of receptors available for the drug or neurotransmitter to bind to. This depletion is caused by the cell's reducing the number of receptors in response to their saturation.
Examples: Amphetamine

Amphetamine

Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

, ephedrine

Ephedrine

Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

, MDMA (indirectly acting drugs)

Tachyphylaxis is characterized by the rate sensitivity: The response of the system depends on the rate with which a stimulus is presented. To be specific, 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, in general, 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. The following schematic represents the activity:



         p

   A --------> B

Where p is the activation rate coefficient. It is customary that 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 offer particular use of such (mathematical) models in endocrinology, physiology and pharmacology.

Examples

Examples of tachyphylaxes are the following:

Calcitonin
Calcitonin
Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...

demonstrates tachyphylaxis in 2–3 days when being used to treat hypercalcemia of malignancy. This reaction is anticipated and calcitonin is given along with biphosphonates, which have their maximum effect in 2–3 days. (5)

Nitroglycerine demonstrates tachyphylaxis, requiring drug-free intervals when administered transdermally
Repeated doses of ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

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 released than the initial dose.
Nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...

may also show tachyphylaxis over the course of a day, although the mechanism of this action is unclear.
Hydralazine
Hydralazine
Hydralazine is a direct-acting smooth muscle relaxant used to treat hypertension by acting as a vasodilator primarily in arteries and arterioles...

displays tachyphylaxis if given as a monotherapy for antihypertensive treatment. It is administered with a beta-blocker with or without a diuretic.
Metoclopramide
Metoclopramide
Metoclopramide is an antiemetic and gastroprokinetic agent. It is commonly used to treat nausea and vomiting, to facilitate gastric emptying in people with gastroparesis, and as a treatment for the gastric stasis often associated with migraine headaches.-Medical uses:Metoclopramide is commonly...

is another example.
Dobutamine
Dobutamine
Dobutamine is a sympathomimetic drug used in the treatment of heart failure and cardiogenic shock. Its primary mechanism is direct stimulation of β1 receptors of the sympathetic nervous system. Dobutamine was developed by a laboratory led by Drs...

, a direct-acting beta agonist used in congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

, also demonstrates tachyphylaxis.
Desmopressin
Desmopressin
Desmopressin is a synthetic replacement for vasopressin, the hormone that reduces urine production. It may be taken nasally, intravenously, or as a tablet...

used in the treatment of type 1 von Willebrand disease
Von Willebrand disease
von Willebrand disease is the most common hereditary coagulation abnormality described in humans, although it can also be acquired as a result of other medical conditions. It arises from a qualitative or quantitative deficiency of von Willebrand factor , a multimeric protein that is required for...

is, in general, given every 12–24 hours in limited numbers due to its tachyphylactic properties.
Hormone replacement
Hormone replacement therapy (menopause)
Hormone replacement therapy is a system of medical treatment for surgically menopausal, perimenopausal and to a lesser extent postmenopausal women...

when used in menopausal women in the form of estrogen and progesterone implants is cited as having potential to lead to tachyphylaxis, but that citation is based on a single study done in 1990 and no followup research is available to support this interpretation.
Psychedelics such as LSD-25 and psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...

-containing mushrooms demonstrate very rapid tachyphylaxis. In other words, one may be unable to 'trip
Psychedelic experience
The term "psychedelic experience" is vague – characterized by polyvalence or ambiguity due to its nature – however in modern psychopharmacological science as well as philosophical, psychological, neurological, spiritual-religious and most other ideological discourses it is understood as an altered...

' two days in a row. Some people are able to 'trip' by taking up to three times the dosage, yet some users may not be able to negate tachyphylaxis at all until a period of days has gone by.
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, in general, leveling off after day 7. Whether this is caused directly by opioid receptors modified 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.

Examples

See also