Tachyphylaxis: Causes, Symptoms, Diagnosis and Treatment

The tachyphylaxis It is the phenomenon of tolerance to the action of a drug that occurs acutely and quickly. It is usually caused by prolonged exposure to the same pharmacological 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 given by a continuous stimulation to the biochemical receptors on which the drugs act. The continuous stimulation of receptors with agonists gives rise to this phenomenon.

Drugs that bind physiological receptors and simulate the regulatory effects of an endogenous signaling compound are referred to as agonists. 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, which 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 he receives 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; In tachyphylaxis, tolerance is rapid and acute, while pharmacological tolerance is a gradual process.

Desensitization may result in the recipient being temporarily inaccessible to the drug or the synthesis of receptors decreasing and, therefore, there will be fewer receptors available on the cell surface.

Causes

Structural modification of the receivers

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

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

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

Decrease in the number of receivers

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 into the membrane.

As there is a smaller number of surface receptors to be coupled with the agonists, the doses administered to achieve the necessary plasma concentrations are increasing, generating tachyphylaxis.

Increased metabolic degradation

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

When metabolized more rapidly, plasma concentrations decrease progressively and the rate of replacement when receiving equal doses can not compensate for this decrease.

Physiological adaptation

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

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

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

symptom

The symptoms of tachyphylaxis are basically limited to the absence of effect by the medication that is administered; therefore, it is common the persistence of the symptomatology that is tried to improve in spite of continuing the administration of the drug.

Symptoms compatible with withdrawal symptoms have been described despite continued administration of the drug, especially in patients receiving antidepressants and opiates.

Diagnosis

For the diagnosis of tachyphylaxis, the symptoms of drug tolerance 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.

Taquilaxia requires increases of the doses to reach the same effects that initially were 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 the initial functional tolerance to the drug.

Treatment

There is no treatment that prevents or regulates tachyphylaxis. The patient who presents this condition must be identified and weigh the possibility of increasing the doses until the desired effect or the change in the medication is achieved in order to avoid toxic doses.

In some cases the medication can be doubled or tripled, if the risk of toxicity does not exist with these 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 must 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 action of Drugs. (2012) P. 68
2. Freeman, B; Berger, J. Anesthesiology Core Review. Part One: Basic Exam. Mc Graw Hill. Chapter 43: Drug Tolerance and Tachyphylaxis. Retrieved 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). Retrieved from: cdn.doctorsonly.co.il