Diphenhydramine hydrochloride

32115530

Diphenhydramine, a sedating antihistamine, is an agonist of human bitter taste receptor 14 (hTAS2R14). Diphenhydramine hydrochloride (DPH) was used as a model bitter medicine to evaluate whether the umami dipeptides (Glu-Glu and Asp-Asp) and their constituent amino acids (Glu, Asp) could suppress its bitterness intensity, as measured by human gustatory sensation testing and using the artificial taste sensor. Various concentrated (0.001-5.0 mM) Glu-Glu, Asp-Asp, Glu and Asp significantly suppressed the taste sensor output of 0.5 mM DPH solution in a dose-dependent manner. The effect of umami dipeptides and their constituent amino acids was tending to be ranked as follows, Asp-Asp > Glu-Glu >> Gly-Gly, and Asp > Glu >> Gly (control) respectively. Whereas human bitterness intensity of 0.5 mM DPH solution with various concentrated (0.5, 1.0, 1.5 mM) Glu-Glu, Asp-Asp, Glu and Asp all significantly reduced bitterness intensity of 0.5 mM DPH solution even though no statistical difference was observed among four substances. The taste sensor outputs and the human gustatory sensation test results showed a significant correlation. A surface plasmon resonance study using hTAS2R14 protein and these substances suggested that the affinity of Glu-Glu, Asp-Asp, Glu and Asp for hTAS2R14 protein was greater than that of Gly-Gly or Gly. The results of docking-simulation studies involving DPH, Glu-Glu and Asp-Asp with hTAS2R14, suggested that DPH is able to bind to a space near the binding position of Glu-Glu and Asp-Asp. In conclusion, the umami dipeptides Glu-Glu and Asp-Asp, and their constituent amino acids, can all efficiently suppress the bitterness of DPH.

docking simulation; human bitterness-suppressing agent; surface plasmon resonance study; taste sensor; umami-peptide.

Bitterness-Suppressing Effect of Umami Dipeptides and Their Constituent Amino Acids on Diphenhydramine: Evaluation by Gustatory Sensation and Taste Sensor Testing

Takayoshi Okuno 1, Shiori Morimoto 1, Haruka Nishikawa 1, Tamami Haraguchi 1, Honami Kojima 1, Hirofumi Tsujino 2, Mitsuhiro Arisawa 2, Taku Yamashita 1, Junichi Nishikawa 1, Miyako Yoshida 1, Masaaki Habara 3, Hidekazu Ikezaki 3, Takahiro Uchida 1

2020;

32070459

A 62-year-old patient living in a rural community was referred to participate in a pharmacist-led home visit program because of concerns with the patient’s increasing falls and medication complexity. The patient reported experiencing an increasing number of falls over the past few months, resulting in a recent hospitalization and mild head trauma. The patient’s past medical history included diabetes mellitus type 2, hypertension, hyperlipidemia, gastroesophageal reflux disease, paroxysmal atrial fibrillation, unspecified back pain, and benign prostatic hyperplasia. During the comprehensive medication review, pharmacists determined the patient had inadvertently purchased an acetaminophen/ diphenhydramine combination medication, rather than his usual acetaminophen. According to the 2019 Beers criteria, use of acetaminophen/diphenhydramine for back pain without insomnia is not the best option and may contribute to falls. With an estimated four to eight tablets per day, the patient was taking 200-400 mg of diphenhydramine daily. Pharmacist recommendations included contacting the prescribing physician to obtain a prescription for acetaminophen. By asking the local pharmacy to dispense acetaminophen as a prescription, the risk of the patient inadvertently purchasing an inappropriate product is reduced. After removing the diphenhydramine from the patient’s regimen, the falls ceased. This case demonstrates the effects of inappropriate diphenhydramine use in an especially vulnerable population. It also highlights the critical role that rural community pharmacists can play in improving their patients’ health care.

Patient Fall Risk Caused by Unintended Diphenhydramine Use

Kimberly C McKeirnan, Kyle R Frazier, Andrew A Yabusaki

2020 Mar 19;