Gli aggiornamenti su Difenidramina cloridrato riguardano i campi di applicazione e le possibili controindicazioni.

Okuno T, Morimoto S, Nishikawa H, et al. Bitterness-Suppressing Effect of Umami Dipeptides and Their Constituent Amino Acids on Diphenhydramine: Evaluation by Gustatory Sensation and Taste Sensor Testing. Chem Pharm Bull (Tokyo). 2020;68(3):234–243. doi:10.1248/cpb.c19-00736

Abstract. 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.

Dahal A, Neupane R, Boddu SH, Renukuntla J, Khupse R, Dudley R. Percutaneous Absorption of Lorazepam, Diphenhydramine Hydrochloride, and Haloperidol from ABH Gel. Int J Pharm Compd. 2020 Mar-Apr;24(2):168-175. 

Abstract. The objective of this project was to study the percutaneous absorption of lorazepam, diphenhydramine hydrochloride, and haloperidol from a topical Pluronic lecithin organogel, also known as ABH gel, across the porcine ear skin and verify its suitability for topical application. ABH gel was prepared using lecithin in isopropyl palmitate solution (1:1) as an oil phase and 20% w/v Poloxamer 407 solution as an aqueous phase. The gel was characterized for pH, viscosity, drug content, and thermal behavior. A robust high-performance liquid chromatography method was developed and validated for simultaneous analysis of lorazepam, diphenhydramine hydrochloride, and haloperidol. The percutaneous absorption of lorazepam, diphenhydramine hydrochloride, and haloperidol from ABH gel was carried out using Franz cells across the Strat-M membrane and pig ear skin. The pH of ABH gel was found to be 5.66 ± 0.13. The retention time of diphenhydramine hydrochloride, haloperidol, and lorazepam was found to be 5.2 minutes, 7.8 minutes, and 18.9 minutes, respectively. The ABH gel was found to be stable for up to 30 days. Theoretical steady state plasma concentrations (CSS) of diphenhydramine hydrochloride, haloperidol, and lorazepam calculated from flux values were found to be 1.6 ng/mL, 0.13 ng/mL, and 2.30 ng/mL, respectively. The theoretical CSS of diphenhydramine hydrochloride, haloperidol, and lorazepam were much lower than required therapeutic concentrations for antiemetic activity to relieve chemotherapy-induced nausea and vomiting. From the percutaneous absorption data, it was evident that ABH gel failed to achieve required systemic levels of lorazepam, diphenhydramine hydrochloride, and haloperidol following topical application. Copyright© by International Journal of Pharmaceutical Compounding, Inc

Melnikova M, Wauer US, Mendus D, et al. Diphenhydramine increases the therapeutic window for platinum drugs by simultaneously sensitizing tumor cells and protecting normal cells . Mol Oncol. 2020;10.1002/1878-0261.12648. doi:10.1002/1878-0261.12648

Abstract. Platinum-based compounds remain a well-established chemotherapy for cancer treatment despite their adverse effects which substantially restrict the therapeutic windows of the drugs. Both the cell type-specific toxicity and the clinical responsiveness of tumors have been associated with mechanisms that alter drug entry and export. We sought to identify pharmacological agents that promote cisplatin (CP) efficacy by augmenting the levels of drug-induced DNA lesions in malignant cells and simultaneously protecting normal tissues from accumulating such damage and from functional loss. Formation and persistence of platination products in the DNA of individual nuclei were measured in drug-exposed cell lines, in primary human tumor cells and in tissue sections using an immunocytochemical method. Using a mouse model of CP-induced toxicity, the antihistaminic drug diphenhydramine (DIPH) and two methylated derivatives decreased DNA platination in normal tissues and also ameliorated nephrotoxicity, ototoxicity, and neurotoxicity. In addition, DIPH sensitized multiple cancer cell types, particularly ovarian cancer cells, to CP by increasing intracellular uptake, DNA platination, and/or apoptosis in cell lines and in patient-derived primary tumor cells. Mechanistically, DIPH diminished transport capacity of CP efflux pumps MRP2, MRP3, and MRP5 particularly in its C2+C6 bimethylated form. Overall, we demonstrate that DIPH reduces side effects of platinum-based chemotherapy and simultaneously inhibits key mechanisms of platinum resistance. We propose that measuring DNA platination after ex vivo exposure may predict the responsiveness of individual tumors to DIPH-like modulators. © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Kuruvilla M, Sexton M, Wiley Z, Langfitt T, Lynde GC, Wolf F. A Streamlined Approach to Optimize Perioperative Antibiotic Prophylaxis in the Setting of Penicillin Allergy Labels . J Allergy Clin Immunol Pract. 2019;S2213-2198(19)31050-5.

Abstract. Background: Patients with penicillin allergy labels often receive alternative antibiotics for perioperative prophylaxis, as opposed to first-line cephalosporins (cefazolin/cefuroxime). Provider misconceptions about the risk of cross-reactivity likely drive this prescribing behavior, which is problematic because of its association with increased risk of surgical-site infections. Objective: To develop, implement, and assess the safety of a streamlined approach to perioperative antibiotic selection for surgical patients with a penicillin allergy label, to reduce the use of second-line antibiotics....Conclusions: Using a streamlined algorithm, we were able to significantly reduce the use of second-line antibiotics in penicillin-allergic surgical patients without severe adverse reactions. Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. 

Li YY, Zeng YS, Chen JY, et al. Prophylactic diphenhydramine attenuates postoperative catheter-related bladder discomfort in patients undergoing gynecologic laparoscopic surgery: a randomized double-blind clinical study. J Anesth. 2020;34(2):232–237. doi:10.1007/s00540-019-02724-3

Abstract. Background: To evaluate the effectiveness of diphenhydramine, an antihistamine with anti-muscarinic properties, for prevention of postoperative catheter-related bladder discomfort (CRBD)....Conclusion: Prophylactic diphenhydramine 30 mg at induction of general anesthesia reduced the incidence and severity of postoperative bladder discomfort without significant side effects in patients receiving gynecologic laparoscopic surgery.

Fein MN, Fischer DA, O'Keefe AW, Sussman GL. CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria. Allergy Asthma Clin Immunol. 2019;15:61. Published 2019 Oct 1. doi:10.1186/s13223-019-0375-9

Abstract. Oral H1-antihistamines (AHs) are the most commonly used therapy to treat allergic rhinitis and chronic urticaria. Older, first-generation AHs (e.g. diphenhydramine, hydroxyzine) have significant and common side effects including sedation, impairment with decreased cognitive function, poor sleep quality, dry mouth, dizziness, and orthostatic hypotension. These drugs have also been found to result in death from accidents, intentional or unintentional overdoses, and sudden cardiac death. The unfavourable risk-benefit profile of first-generation AHs led to the development of newer, less-sedating second- and third-generation AHs, which first became available in Canada in the 1980s. High-quality trials have proven that newer generation AHs are superior in safety compared to older first-generation AHs. On average, they have improved potency and efficacy. Second- and third-generation AHs are the recommended first-line treatment for mild allergic rhinitis and acute and chronic urticaria. Despite this evidence, older first-generation AHs continue to be over-utilized because of their over-the-counter (OTC) status and long history of use. The Canadian Society of Allergy Clinical Immunology (CSACI) recommends that newer generation AHs should be preferred over first-generation AHs for the treatment of allergic rhino-conjunctivitis and urticaria. To promote this recommendation, education of health professionals and the public is necessary. Further, given the dangers of older first-generation AHs, we believe they should be used only as a last resort with eventual consideration given to having them only available behind the counter in pharmacies. © The Author(s) 2019.

Sabins D, Diep T, McCartan P, Patel S, Zhao F. Stability and Compatibility of Diphenhydramine Hydrochloride in Intravenous Admixtures: A New Look at an Old Drug. Hosp Pharm. 2019;54(5):330–334. doi:10.1177/0018578718802586

Abstract. Purpose: Intravenous (IV) admixtures of diphenhydramine are widely used in hospitalized patients to prevent or treat hypersensitivity reactions. However, there is limited data to support the admixture preparation in this manner. This study was designed to investigate the stability and compatibility of diphenhydramine in IV admixtures with a goal to establish a 14-day beyond-use dating with storage under refrigeration. Methods: The commercially available 50 mg/mL diphenhydramine hydrochloride injection vials were used to prepare the 0.2 and 1.0 mg/mL IV admixtures in 0.9% sodium chloride injection and 5% dextrose injection in 50 mL polyvinyl chloride (PVC) bags. The IV bags were sealed and stored under refrigeration (2°C-8°C) for the stability study. At each predetermined time point, samples were taken for visual inspection, pH measurement, and analysis by a stability-indicating high-performance liquid chromatography (HPLC) method. Results: The freshly prepared IV admixtures appeared clear, colorless, and particulate-free with pH readings of 4.44 to 4.60. The initial drug concentrations of all samples were confirmed by HPLC to be within 101.8% to 103.6% of the label claims. Over the 14 days of the study period, there was no significant change in the appearance or pH values for all stability samples. The HPLC results also confirmed that there was no more than ±2% change of the initial drug concentration in any stability samples. Conclusion: Diphenhydramine hydrochloride IV admixtures of 0.2 and 1.0 mg/mL are compatible with 0.9% sodium chloride injection and 5% dextrose injection in PVC bags. These IV admixtures are stable chemically and physically for up to 14 days when stored under refrigeration (2°C-8°C).

Pan W, Cao Z, Liu D, Jiao Y. Protective Effect of Diphenhydramine against Traumatic Brain Injury in Rats via Modulation of Oxidative Stress and Inflammation. Pharmacology. 2020;105(1-2):47–53. doi:10.1159/000502767

Abstract. Background: Traumatic brain injury (TBI) is considered a major burden across the globe affecting both individuals and their families. Therefore, the present study was conducted to determine the protective effect of diphenhydramine (DPM) against TBI in experimental rats....Results: Results of the study suggest that DPM causes reduction in CE and prevents neuronal degeneration. It also causes reduction in inflammation and oxidative stress in a dose-dependent manner. The level of Bax was found to be elevated, together with reduction in the Bcl-2 level in the DPM-treated group. Conclusion: DPM exerts a neuroprotective effect after TBI via the attenuation of oxidative stress, inflammation, and mitochondrial apoptosis pathways. © 2019 S. Karger AG, Basel.

Nguyen T, Polyakova B, Cerenzio J, Ramilo JR. Diphenhydramine Use in End-Stage Kidney Disease . Am J Ther. 2019;10.1097/MJT.0000000000001057. doi:10.1097/MJT.0000000000001057

Abstract. Background: Diphenhydramine is commonly used in patients with kidney disease and end-stage kidney disease (ESKD) for sleep, allergic reactions, itching, and dialysis treatment related complications, and misuse associated with diphenhydramine is also reported. Diphenhydramine's pharmacokinetics property is reviewed and discussed....Results: There is lack of studies available for diphenhydramine, kidney disease, and dialysis. There were case reports of diphenhydramine abuse and toxicity due to overdose. Diphenhydramine is highly bound to protein that limits its ability to dialyze, and therefore, it may predispose to side effects. Information on diphenhydramine used in the dialysis population is scarce, and dosing toxicity is unknown. Conclusions: The data available for use of diphenhydramine in ESKD and dialysis are limited. Clinicians should use caution with the use of diphenhydramine in this population. Copyright © 2019 Wolters Kluwer Health, Inc.