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Cough Update: Assessment of Antitussive potential of diphenhydramine on the citric acid aerosol-induced cough response

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eMediNexus    21 February 2021

The current study included 20 healthy volunteer subjects and assessed the effectiveness of 25 mg of diphenhydramine as an antitussive by determining its citric acid aerosol-induced cough response. Inclusion measures for participants was manifestation of a consistent, quantitatively definable response to a 5% citric acid challenge.

These participants were initially administered with either a placebo vehicle or 25 mg diphenhydramine in a 10 ml formulation. The enrolled subjects were challenged at 15, 30, 45, 60, 120, and 240 minutes, subsequent to drug ingestion. After a period of three days, these subjects were given the alternate treatment and re-challenged at the same time points. 

The results revealed that diphenhydramine was efficacious at the earliest time point evaluated, 15 minutes, and sustained effectiveness over the entire 4-hour duration of the test period. There was no significant alteration in mean cough counts from baseline for the placebo vehicle. It was observed that both the putative soothing effect of a liquid formulation or accommodation to the citric acid spray were responsible for all the early and regularly significant activity of diphenhydramine in suppressing the cough response. 

However, the early onset of activity of diphenhydramine may be attributed to its local anesthetic properties or is suggestive of the finding that the dose of diphenhydramine needed for potent antitussive activity is lower than that essential for efficacious antihistaminic activity. Although further studies are required to validate these outcomes by comparing various doses of diphenhydramine with positive controls, a 25 mg dose of diphenhydramine can be considered as an effective antitussive agent.

Source: Packman EW, Ciccone PE, Wilson J, Masurat T. Antitussive effects of diphenhydramine on the citric acid aerosol-induced cough response in humans. Int J Clin Pharmacol Ther Toxicol. 1991 Jun;29(6):218-22. PMID: 1869343.

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