Diphenhydramine hydrochloride

Donepezil: an unusual therapy for acute diphenhydramine overdose.[Pubmed:30898954]

BMJ Case Rep. 2019 Mar 20;12(3). pii: 12/3/e226836.

An elderly man presented with the history of Diphenhydramine hydrochloride overdose as a suicidal attempt. At presentation, he was in an acute confusional state with several anticholinergic features and had to be managed in intensive care unit. As an antidote for Diphenhydramine hydrochloride, donepezil was used instead of physostigmine due to the unavailability of physostigmine in Bangladesh. The patient improved within the next 24 hours; his level of consciousness improved and the anticholinergic features regressed.

Block of potassium currents in guinea pig ventricular myocytes and lengthening of cardiac repolarization in man by the histamine H1 receptor antagonist diphenhydramine.[Pubmed:9918600]

J Pharmacol Exp Ther. 1999 Feb;288(2):858-65.

Treatment with second generation histamine H1 receptor antagonists has been associated with lengthening of the Q-T interval and proarrhythmia. Similarly, lengthening of the Q-T interval has been reported in patients after overdosing with diphenhydramine (DPH), a first generation agent. Therefore, our study was designed 1) to assess effects of DPH on cardiac repolarization and 2) to characterize effects of the drug on major voltage-dependent cardiac K+ currents. First, we noticed that oral administration of DPH at usual dosages to healthy volunteers or to patients (prior to angioplasty) was associated with prolongation of the Q-Tc interval. Although this effect was modest in most individuals, Q-Tc was increased more than 20 ms in 7 of 20 patients. Second, we noticed that exposure of isolated guinea pig hearts to DPH 10(-5) M caused a lengthening of monophasic action potential duration. This effect was potentiated by the combined perfusion of other K+ channel blockers such as indapamide. Finally, experiments performed with the patch-clamp technique demonstrated unequivocal block of the rapid component of the delayed rectifier (IKr) by DPH; however, IC50 determined for block of IKr (3 x 10(-5) M) is approximately 40-fold greater than plasma concentrations of the drug measured at usual dosages (7 x 10(-7) M). Consequently, in agreement with the long-term clinical use of the drug, prolongation of cardiac repolarization should be minimal in most patients at usual dosages but may be observed with overdosing. Nevertheless, caution remains since excessive lengthening of cardiac repolarization may occur after administration of DPH with other drugs due to 1) concomitant block of other ionic currents or 2) pharmacokinetic interactions leading to toxic concentrations of DPH.

Diphenhydramine hydrochloride, a histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations.

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