Anti-histaminergic (H1 antagonists) drugs could be prescribed at low doses for their sedative effects. Nevertheless, some reviews and articles reported a decrease of sedative effect that can occur as soon as 10 days. What could explain that antagonists H1 do not longer lead to sedation after fews days ?
Marie,
The warning label usually states not to operate a motor vehicle or heavy equipment until known how the medication effects you. The body adapts to the chemicals we put in it. Side effects often wane over time. Although I could find no evidence in the literature of receptor up-regulation, this is often a reason for decreased response of a medication.
These me may be helpful:
Church MK, Church DS. Pharmacology of Antihistamines. Indian Journal of Dermatology. 2013;58(3):219-224. doi:10.4103/0019-5154.110832.
Church MK, Maurer M, Simons FE, Bindslev-Jensen C, van Cauwenberge P, Bousquet J, et al. Risk of first-generation H (1)-antihistamines: A GA (2) LEN position paper. Allergy. 2010;65:459–66. [PubMed]
Regards,
Christopher
@Ivan Parra....
Tolerance in the understanding of response to drugs over time may have many causes,and receptor regulation(up or down) can be one of the causes,as can physical and/or psychological dependence.
Genetics also have an important part to play,as does inducible enzyme activity.
In short,tolerance is a general term,but not a specific cause.
.Thank you all for you answers...I willl read the articles..Nevertheless...I know tolerance mechanism with agonist ...but not with antagonists...that s why I do not understand...I do not see how it could be possible...
Diphenhydramine is specifically an inverse agonist, not an antagonist. So it works differently on the receptors than one would expect. it doesn't merely block the site from being activated, but forces the receptor site to provide the opposite effects it normally would.
Not certain why it becomes less effective as a sedative over time. It's one of the few meds for allergies that crosses the blood-brain barrier, which is why it is effective for sedating patients to begin with. But I can't provide more insight as to why it isn't effective after constant use.
Dear Dr Smith, thank you: I should rather say H1 inverse agonists instead of antagonists. The first article that you recommend mentionned: " Tolerance to sedation and psychomotor impairment, although suggested from some studies (14, 32–34), does not necessarily occur (15, 35)".
Dear Dr Flynn, I finally asked clinicians in my hospital : They did not observe any decrease of sedative effects.
So now: I am not certain either of the loss of this sedative effect over time...
But, still: It is very intersting: I could not see how inverse agonists would lead to tolerance mechanisms...Because both (neutral antagonist or inverse agonist) are suppose to induce at least upregulation, and not a desentitization, classically observed in oipoids/benzodiazepine tolerance.
Unless...we can admit that upregulation of a receptor that display constitutive activity may led to tolerance because the constitutive activity due to the upregulation maintains the activity of the receptor, requiring a higher dose to block it ....But to my knowledge such a mechanism has never been described to explain a loss of effect.
Best regards,
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