Быстрая толерантность к лекарствам: тахифилаксия и механизмы развития.

Rapid and short term onset of drug tolerance
Tachyphylaxis (Greek ταχύς, tachys, "rapid", and φύλαξις, phylaxis, "protection") is a medical term describing an acute, sudden decrease in response to a drug after its administration; i. e. a rapid and short term onset of drug tolerance. It can occur after an initial dose or after a series of small doses. Increasing the dose of the drug may be able to restore the original response.

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.

Psychedelics such as LSD, and psilocybin containing mushrooms demonstrate very rapid tachyphylaxis.

In a patient fully withdrawn from opioids, going back to an intermittent schedule or maintenance dosing protocol, a fraction of the old tolerance level will rapidly develop, usually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 therapy is resumed and, in general, leveling off after day 7. Whether this is caused directly by opioid receptors modified in the past or affecting 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.

Inhalation of an agonist for the beta 2 adrenergic receptor, such as salbutamol (albuterol in the US), is the most common treatment for asthma. Polymorphisms of the beta 2 receptor play a role in tachyphylaxis. Expression of the Gly 16 allele (glycine at position 16) results in greater receptor downregulation by endogenous catecholamines at baseline compared to Arg 16. This results in a greater single use bronchodilator response in individuals homozygous for Arg 16 compared to Gly 16 homozygotes. However, with regular beta 2 agonist use, asthmatic Arg 16 individuals experience a significant decline in bronchodilator response. This decline does not occur in Gly 16 individuals. It has been proposed that the tachyphylactic effect of regular exposure to exogenous beta 2 agonists is more apparent in Arg 16 individuals because their receptors have not been downregulated prior to agonist administration.

Nicotine may also show tachyphylaxis over the course of a day, although the mechanism of this action is unclear.

Acute tachyphylaxis which does not carry into the next day has been observed in children taking methylphenidate, and inspired the development of OROS methylphenidate.

Use of intranasal decongestants (such as oxymetazoline) for more than three days leads to tachyphylaxis of response and rebound congestion, caused by alpha adrenoceptor downregulation and desensitization. The mechanism may specifically include receptor internalisation and resistance to endogenous vasoconstrictors causing worsening in symptoms post use of medication. Oxymetazoline induced tachyphylaxis and rebound congestion are reversed by intranasal fluticasone.