Tachyphylaxis is a phenomenon common in chronic illnesses such as atopic dermatitis. It is a major setback to ongoing therapy, and often requires its sufferers to move from one medication class to another. The rate at which the list of effective drugs increases is negligible compared to the rate of therapy failure caused by Tachyphylaxis. It has become imperative to recognise and prevent tachyphylaxis before it sets in.
What is Tachyphylaxis?
Tachyphylaxis is defined as an acute, rapid decline in the pharmacological efficacy of a drug after its administration (1). It is a form of drug tolerance that occurs suddenly. In some rare cases, tachphylaxis occurs after the first dose of medication. Administering a steady dose of a medication over an extended period may cause this desensitization known as Tachyphylaxis, even if the dosage regimen is within acceptable limits.
Mechanism of Tachyphylaxis
The onset of tachyphylaxis seems to be heavily dependent on dose frequency and total time of administration. In the case of the latter, the longer a drug is administered, the higher the possibility of tachyphylaxis. However, as earlier mentioned, there are cases of tachyphylaxis developed after the initial dose.
According to one study which monitored the onset of tachyphylaxis in rats, desensitzation was delayed when the dose frequencies were kept short. It was noted that when the analgesic was allowed to wear off and pain sensation returned, tachyphylaxis occurred faster. It was stated that it is more common to become desensitized to a once-daily regimen than to a three times daily regimen (2). These findings point to the central nervous activity of tachyphylaxis.
Scientists have proposed the possible mechanisms of tachyphylaxis to be receptor saturation and exhaustion of neurotransmitters (3). This claim is plausible when we consider the fact that withholding therapy for a few days or weeks will restore effectiveness.
Is Tachyphylaxis related to Tolerance?
Proponents consider Tachyphylaxis to be a form of tolerance. However, there are some stark differences between the course of action of Tachyphylaxis and that of Tolerance.
Tolerance is defined as a phenomenon where a larger dose is required to produce an equal pharmacological outcome (4). In Tolerance, increasing the dose is enough to maintain pharmacological effectiveness. However, in tachyphylaxis, an increase in dose may or may not have an effect on therapeutic results.
Tolerance, often termed “Acquired Tolerance”, is characterised by physiologic and behavioural tolerance, in which the homeostatic nature of an individual learns to counterbalance the effects of the drug.
Tolerance is not easily resolved with withholding the medication, unlike tachyphylaxis. Tachyphylaxis generally occurs quicker and is more easily resolved than acquired tolerance.
Causes of Tachyphylaxis
Tachyphylaxis may be idiopathic. The following conditions, however, may be a reason for or adjunct to the onset of tachyphylaxis
- Non compliance by patient: tachyphylaxis seems to be worsened by sparse drug administration. This may be caused by a patient who misses too many doses.
- Short duration of use: this outcome is caused by a faulty prescription or an instance where a doctor prescribes a drug for a shorter period than recommended. The recommended dosage of the medication are not sufficient to produce a positive pharmacological output. Instead, it causes a desensitization of the receptors required to facilitate the desired effect.
- Presence of comorbidities: complications of the gastrointestinal tract or impairments to absorption may result in reduced dosage levels of a medication. This on its own may cause a reduction in pharmacological outcomes of therapy, which may be mistaken for tachyphylaxis.
Diagnosis of Tachyphylaxis
The approach taken to identify tachyphylaxis often involves enquiring into the patient’s drug compliance levels. The physician may be concerned about the following:
- How you took the first dose of the medication
- How many hours interval you leave between doses
- How your condition improved or worsened during and after administration.
In many drug therpaies, the first dose is twice the regular dose. This provides a form of “jump-start”. If this is neglected, the progression of therapy may be negatively affected. If this is the case, restarting the modulation will fix the issue.
If the underlying condition continues to worsen even after restarting therapy, it is an indication that Tachyphylaxis, not drug compliance, may be present.
Types of tachyphylaxis
Desensitization is classified based on the medication it affects.
- Nasal decongestants:The continuous administration of nasal decongestants like oxymetazoline, may cause a rebound decongestion due to tachyphylaxis. Nasal decongestants provide vasoconstriction but also downregulate the alpha adrenergic system. This triggers desensitization which may worsen initial symptoms
- Beta 2 Agonists: medications like Salbutamol are commonly used in the treatment of asthma. Asthma treatments are classified as Preventers and Controllers. Salbutamol is considered a short acting controller used when an asthma attack has begun. Aside from its short duration of action, salbutamol may not be recommended for continuous use because of the risk of tachyphylaxis and desensitization.
- Psychedelics: Psilocybin-containing mushrooms and Lysergic Derivative Acid (LSD-25) are prone to sudden tachyphylaxis. These substances are favoured for their psychoactive properties. When tachyphylaxis sets in, these effects may not be experienced, even with double or triple the regular dose. A period of at least 2 days may be necessary to regain sensitivity.
How does Tachyphylaxis relate to Topical Steroid Withdrawal (TSW)
The possibility of tachyphylaxis to Topical steroids is new. More research and evidence is required to validate a link between the two.
Topical Steroid Withdrawal (TSW) is a skin condition that occurs when a topical corticosteroid is abruptly discontinued. One study (5) postulated that tachyphylaxis may be one of the leading causes of TSW in atopic dermatitis. The study notes that tachyphylaxis leading to TSW was more prominent in atopic dermatitis than in pruritus, despite the fact that they are both managed with steroids.
According to the study’s findings, the reduced sensitivity to topical steroids after prolonged administration may produce symptoms similar to steroid withdrawal, even while steroids are still in use. Thus, a patient may begin to experience Topical Steroid Withdrawal while still using the steroid because desensitization has occurred.