TACHYPHYLAXIS: CAUSES, SYMPTOMS, DIAGNOSIS AND TREATMENT - MEDICINE - 2024

The tachyphylaxis is the phenomenon of tolerance to drug action that occurs acutely and quickly. It is usually caused by prolonged exposure to the same drug stimulation, which is characterized by a rapid decrease in the effect of said drug.

Also known as desensitization, adaptation, lack of response or down regulation, tachyphylaxis is caused by a continuous stimulation of the biochemical receptors on which the drugs act. Continuous stimulation of the receptors with agonists gives rise to this phenomenon.

Agonists are drugs that bind to physiological receptors and simulate the regulatory effects of an endogenous signaling compound. For example, when a patient is allergic to a drug, desensitization therapy can be performed.

In this therapy, tiny doses of the drug are administered that are increased very slowly and continuously, until reaching the full doses required by the patient. In this way, knowledge of pharmacodynamics is used to desensitize the patient and ensure that they receive the necessary treatment.

It is important to differentiate the terms tolerance and tachyphylaxis. It can be said that tachyphylaxis is a type of pharmacological tolerance; tolerance is rapid and acute in tachyphylaxis, whereas drug tolerance is a gradual process.

Desensitization can result in the receptor being temporarily inaccessible to the drug or receptor synthesis decreases and thus fewer receptors will be available on the cell surface.

Causes

Structural modification of receptors

Receptors initiate the regulation of biochemical events and physiological functions and are subject to multiple homeostatic and regulatory controls.

As a homeostatic cellular protection response to excessive stimulation, a change in the receptor configuration occurs that causes the inability to form the agonist-receptor complex or, conversely, a strong binding with the agonist without opening the ion channel.

When there is phosphorylation of the receptors, their ability to activate the second messenger cascade is altered, although their structure still allows them to couple to the agonist molecule.

Decreased number of receptors

When there is a prolonged exposure to agonists, the organism interprets that there are many receptors on the cell surface and, by endocytosis, the receptors that are "in excess" pass to the interior of the membrane.

As there are fewer surface receptors to couple with the agonists, the doses administered to achieve the necessary plasma concentrations are increasing, generating tachyphylaxis.

Increased metabolic breakdown

Repeated exposure to the same dose of some drugs produces a gradually decreasing plasma concentration, as a consequence of increased metabolic breakdown of the drug in the body.

As it is metabolized faster, plasma concentrations progressively decrease and the rate of replacement when receiving equal doses cannot compensate for this decrease.

Physiological adaptation

Physiological adaptation is more a cause of tolerance than tachyphylaxis, as it is more gradual in some drugs.

However, the mechanism serves to explain some cases of tachyphylaxis, since some pharmacological effects may decrease as a result of a homeostatic response of the body.

An example of this is the hypotensive effect of thiazide diuretics, which is limited by the activation of the renin-angiotensin-aldosterone system.

Symptoms

The symptoms of tachyphylaxis are basically limited to the lack of effect from the medicine being administered; therefore, the persistence of symptoms that attempts to improve despite continuing drug administration is common.

Symptoms consistent with withdrawal symptoms have been described despite continued drug administration, especially in patients receiving antidepressants and opioids.

Diagnosis

For the diagnosis of tachyphylaxis, the symptoms of tolerance to the drug must be differentiated from the signs and symptoms of dependence, which although both coexist and have similar cellular mechanisms, do not refer to the same concept and the implications of both are very different.

Tachylaxis requires dose increases to achieve the same effects that were initially achieved with lower doses. However, in dependence there is a compulsive need for the individual to use the drug to function normally.

In cases of dependence, the brain adapts to high levels of the drug continuously and appears to function normally due to initial functional tolerance to the drug.

Treatment

There is no treatment that prevents or regulates tachyphylaxis. The patient with this condition should be individualized and the possibility of increasing the doses must be considered until the desired effect is achieved or the change in medication to avoid toxic doses.

In some cases the drug can be doubled or tripled, if the risk of toxicity does not exist with those doses and if the risk-benefit ratio allows it.

In other cases, the risk of intoxication does not allow a continuous increase in the dose of the drug, and the medication should be changed to a second-choice medication that can obtain the desired initial effect more slowly.

References

1. Goodman & Gilman. The pharmacological bases of therapeutics. MC Graw Hill. 12th Edition. Chapter 3. Pharmacodynamics: Molecular Mechanisms of Drug Action. (2012) P. 68
2. Freeman, B; Berger, J. Anesthesiology Core Review. Part One: Basic Exam. Mc Graw Hill. Chapter 43: Drug Tolerance and Tachyphylaxis. Recovered from: accessanesthesiology.mhmedical.com
3. Steven Targum. Identification and Treatment of Antidepressant Tachyphylaxis. US National Library of Medicine. National Institutes of Health. Innov Clin Neurosci. 2014 Mar-Apr; 11 (3-4): 24–28. Published online Mar-Apr 2014. Retrieved from: nlm.nih.gov
4. Gregory Katz, MD. Tachyphylaxis / Tolerance to Antidepressive Medications: A Review. Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011). Recovered from: cdn.doctorsonly.co.il