Network pharmacology combined with Mendelian randomization analysis to identify the key targets of renin-angiotensin-aldosterone system inhibitors in the treatment of diabetic nephropathy.

Background: Diabetic Nephropathy (DN) is one of the microvascular complications of diabetes. The potential targets of renin-angiotensin-aldosterone system (RAAS) inhibitors for the treatment of DN need to be explored. Methods: The GSE96804 and GSE1009 datasets, 729 RAAS inhibitors-related targets and 6,039 DN-related genes were derived from the public database and overlapped with the differentially expressed genes (DN vs. normal) in GSE96804 to obtain the candidate targets. Next, key targets were screened via the Mendelian randomization analysis and expression analysis. The diagnostic nomogram was constructed and assessed in GSE96804. Additionally, enrichment analysis was conducted and a 'core active ingredient-key target-disease pathway' network was established. Finally, molecular docking was performed. Results: In total, 60 candidate targets were derived, in which CTSC and PDE5A were screened as the key targets and had a causal association with DN as the protective factors (P < 0.05, OR < 1). Further, a nomogram exhibited pretty prediction efficiency. It is indicated that Benadryl hydrochloride might play a role in the DN by affecting the pathways of 'cytokine cytokine receptor interaction', etc. targeting the CTSC. Moreover, PDE5A might be involved in 'ECM receptor interaction', etc. for the effect of NSAID, captopril, chlordiazepoxide on DN. Molecular docking analysis showed a good binding ability of benadryl hydrochloride and CTSC, NSAID and PDE5A. PTGS2, ITGA4, and ANPEP are causally associated with acute kidney injury. Conclusion: CTSC and PDE5A were identified as key targets for RAAS inhibitors in the treatment of DN, which might provide some clinical significance in helping to diagnose and treat DN. Among the targets of RAAS inhibitors, PTGS2, ITGA4 and ANPEP have a causal relationship with acute kidney injury, which is worthy of further clinical research.

Retrospective review of diphenhydramine vs diphenhydramine plus glucocorticoid for the treatment of allergic reaction in cats.

OBJECTIVES: The aims of the present study were to report the outcomes of treating allergic reactions in cats with diphenhydramine vs diphenhydramine plus glucocorticoid and to determine whether signs recurred or additional veterinary intervention was needed in the days after initial treatment. METHODS: This retrospective study evaluated 73 cats treated for allergic reaction with diphenhydramine alone or in combination with a glucocorticoid at a 24 h emergency and specialty referral veterinary hospital between 1 January 2012 and 31 March 2021. RESULTS: In total, 44 cats were treated with diphenhydramine alone, and 29 were treated with diphenhydramine plus dexamethasone sodium phosphate. The inciting cause was known or highly suspected in 50 patients. Vaccines were the most common (31 patients), followed by insect envenomation (17 cases). No cat in either group progressed to anaphylaxis. There was no difference in resolution of clinical signs between the groups. Follow-up contact was successfully made with 40/73 cat owners. All 40 cats were alive. Eight had persistent signs. There was no difference in the number of cats with persistent signs between groups. Five cats required additional treatment after the initial emergency visit. There was no difference between the two groups for persistent signs at follow-up. CONCLUSIONS AND RELEVANCE: There was no difference in measured outcomes between cats treated with diphenhydramine alone vs those treated with a glucocorticoid in addition to diphenhydramine in this population. The ideal treatment for allergic reactions is unknown. Based on currently available data in human and veterinary literature, glucocorticoids are not indicated to treat acute allergic reactions. The role of antihistamines as part of a symptomatic supportive treatment plan to shorten the duration of signs is unclear at this time and may be considered.

An unusual case of fatal hypothermia involving topical diphenhydramine.

PURPOSE: Diphenhydramine is an antihistamine drug widely used to alleviate symptoms caused by allergies and the common cold. Diphenhydramine-involved fatalities have been reported in the past but usually involving overdose by ingestion. We report a peculiar case of fatal hypothermia during non-winter season involving topical diphenhydramine. METHODS: A 23-year-old male with no known preexisting medical conditions was found dead in the bathroom of his apartment with a small amount of running water on his back. Postmortem examinations and toxicological analysis on blood and urine were performed. RESULTS: Color difference was apparent between the right and left cardiac blood. Wischnewski spots were observed in the gastric mucosa. Histological examination revealed no obvious findings that could attribute to serious cardiovascular events. Drug screening by gas chromatograph-tandem mass spectrometry (GC/MS/MS) detected diphenhydramine in blood and urine. Further quantification revealed the postmortem concentrations to be 0.44 µg/mL in blood and 2500 µg/mL in urine. CONCLUSIONS: The cause of death was determined to be hypothermia. Diphenhydramine-induced drowsiness and possible intrinsic cardiac factor may have led to prolonged impaired consciousness, preventing his ability to escape from the running cold water leading to hypothermia and death.

Adjuvant anticholinergic therapy for the prevention of akathisia in patients with primary headache in the emergency department: A systematic review.

OBJECTIVES: Adjunct therapy with anticholinergic agents has been proposed to reduce the incidence of extrapyramidal side effects such as akathisia following treatment with neuroleptics or metoclopramide. This systematic review assessed the effectiveness of anticholinergic agents to prevent neuroleptic or metoclopramide-induced akathisia in patients presenting to the emergency department (ED) with benign headache. METHODS: Eight electronic databases and the gray literature were searched to identify randomized controlled trials involving adult patients presenting to the ED with primary headache treated with neuroleptic or metoclopramide. Study selection, data extraction, and quality assessment were completed by two independent reviewers. Individual or pooled meta-analysis of dichotomous outcomes were calculated as relative risks (RRs) with 95% confidence intervals (CIs) using a random-effects model. Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 1032 studies were screened, of which two studies were included in the review. Both studies provided patients with diphenhydramine following treatment with neuroleptics or metoclopramide. Treatment with diphenhydramine did not reduce the incidence of akathisia compared to treatment with placebo (RR 0.83, 95% CI 0.43-1.61, I2  = 0%). The impact of diphenhydramine on pain relief, need for rescue medications, and relief of other extrapyramidal side effects was reported in one of the two studies, with no significant differences noted in any outcomes compared to patients treated with placebo. CONCLUSION: This review found insufficient evidence to recommend the use of diphenhydramine as an adjunct therapy to prevent akathisia in ED patients treated with neuroleptics or metoclopramide for primary headache. This finding relies on the results of two small randomized controlled trials with incomplete outcome reporting. Additional high-quality studies are needed to better understand the clinical efficacy of agents with anticholinergic properties in the ED management of patients with primary headaches.

[Treatment of sleep disturbances associated with chronic non-specific low back pain: results of prospective randomized multicenter open-label clinical trial]. / Lechenie narushenii sna, svyazannykh s ostrym nespetsificheskim bolevym sindromom v poyasnichno-kresttsovom otdele spiny: rezul'taty prospektivnogo mnogotsentrovogo randomizirovannogo otkrytogo sravnitel'nogo v parallel'nykh gruppakh klinicheskogo issledovaniya.

OBJECTIVE: A comparative study of the effectiveness and safety of novel combination naproxen sodium and diphenhydramine in subjects with low back pain along with transient insomnia. MATERIAL AND METHODS: It was an open label, randomized, comparative, parallel group and multi-center clinical study. Subjects were randomised into one of three treatment arms: naproxen sodium 440 mg/diphenhydramine 50 mg, naproxen sodium 550 mg, Paracetamol 1000 mg/diphenhydramine 50 mg. All the subjects were advised to apply study drug ones before sleep for 3 days. All subjects also received naproxen sodium 275 mg as background therapy. The primary end-point was wake time after sleep onset (WASO) measured by actigraphy. Other secondary sleep and pain end-points were also assessed. RESULTS: Efficacy analysis was performed for intent-to-treat population (n=235 subjects). naproxen sodium 440 mg/diphenhydramine 50 mg combination showed significant improvements in WASO vs. naproxen sodium 550 mg (-42 min p=0.0174), while differences vs. Paracetamol 1000 mg/diphenhydramine 50 mg (-30 min, p=0.0891) were not significant. According to the average pain intensity difference in the lumbosacral spine combination product naproxen sodium 440 mg/diphenhydramine 50 mg was significantly improved compared with naproxen sodium 550 mg (-9.42, p<0.001) and Paracetamol 1000 mg/diphenhydramine 50 (-7.15, p<0.05). CONCLUSION: Naproxen sodium 440 mg/diphenhydramine 50 mg combination demonstrated improvement in sleep maintenance (WASO) vs. naproxen sodium 550 mg and higher efficiency in average daily pain reduction compared with the comparison groups. The treatment was well tolerated There were no serious or unexpected adverse events reported in the study.

A Pilot Study of Transdermal Application of Diphenhydramine to the Nasal Ala in Patients with Allergic Rhinitis and Asthma.

BACKGROUND: To date, topical allergic rhinitis drugs must be applied intranasally. We studied the efficacy, safety, and impact on co-existing asthma symptoms of transdermal delivery of diphenhydramine through the nasal ala. METHODS: We enrolled outpatients with symptomatic allergic rhinitis and asthma who were on stable medication for at least 4 weeks. Patients applied diphenhydramine ointment, 0.07 g measured with weighing spoon (0.7 mg diphenhydramine), to the nasal ala twice a day for 2 weeks, followed by 2 weeks' washout. Effects were assessed with the Japanese Allergic Rhinitis Standard Quality of Life Questionnaire (JRQLQ) and Self-assessment of Allergic Rhinitis and Asthma (SACRA) and Asthma Control Test (ACT) questionnaires. RESULTS: Ten patients participated in the study. Two patients experienced acute exacerbation of asthma during the intervention phase, but no other adverse effects occurred. Self-assessments indicated efficacy in treating nasal symptoms in 5 patients. No significant changes in scores were seen, although mean total JRQLQ score showed a numerical improvement (from 34.3 [21.0] to 14.4 [8.8]; P = 0.0547). Asthma symptoms improved subjectively in 2 patients. CONCLUSIONS: The efficacy of transdermal application of diphenhydramine on the nasal ala for treating allergic rhinitis was not conclusive, but appears to be effective in certain patients.

Anaphylaxis due to First-Time Intravenous Infusion of N-Acetylcysteine in a Dog.

A 4-year-old female spayed Pomeranian was referred to the emergency service for intermittent trouble breathing and an enlarged liver found on ultrasound. A severe mixed hepatopathy was found on bloodwork, and ultrasound-guided liver aspirates showed marked hepatocellular vacuolar changes and rare neutrophils. An intravenous (IV) loading dose of n-acetylcysteine (NAC) was given for the first time in this patient, and immediately after the infusion the patient collapsed, became hypotensive, hypothermic, tachycardic, and developed gallbladder wall edema. Treatment for anaphylaxis was immediately initiated with IV fluids, an epinephrine bolus and then continuous rate infusion, diphenhydramine, and famotidine. Clinical signs resolved within an hour of treatment with no recurrence. The hepatic enzymopathy improved, and the patient was ultimately diagnosed with a steroid hepatopathy based on laparoscopic liver biopsies. Anaphylaxis caused by first-time administration of IV NAC in a dog has not previously been reported, though it is known to occur in humans. Based on this report, it would be clinically wise to give careful consideration before prescribing NAC in cases where it is not a specific antidote or if other options are available, and to closely monitor the patient during and immediately after administration.

Effect of Honey on Cough Symptoms in Children with Upper Respiratory Tract Infection: A Randomised Controlled Trial.

BACKGROUND AND OBJECTIVE: Cough from URTI is common, leads to discomfort, sleep loss and stress in caregivers, leading to use of ineffective and potentially harmful over-the-counter medications. Honey is cost-effective and safe for children above one year of age. It is readily available and is a potentially valuable demulcent for treatment of childhood cough. The study aimed to determine the effect of honey on cough frequency and severity among children with URTI in outpatient setting. METHODS: A single-blind randomised control trial involving children presenting with cough from URTI attending the GOPC of FMC Keffi. Eighty-four children presenting with cough from URTI were recruited, randomised into two groups of 42 and administered Honey (intervention) and Diphenhydramine (control) in three consecutive bedtime doses. Socio-demographic and clinical data including cough frequency, severity and impact on children and caregivers was collected using Paediatric Cough Questionnaire and Kingston Caregiver Stress Scale tool. Data was analysed using SPSS version 25. A p<0.05 was considered statistically significant. RESULTS: Majority (56.0%) of the participants were males, with a mean age +SD of 4±1.47 years. Median cough frequency score for intervention and control groups pre and post intervention decreased (5.00 and 0.00 vs 5.00 and 3.00, p<0.001). Median cough severity score decreased (4.00 and 0.00 vs 4.00 and 3.00, p<0.001), Post intervention pooled caregivers' burden significantly reduced, (5.00 and 11.00 for intervention and control respectively) and sleep pattern improved among children and caregivers (0.00, 2.00 p<0.001; and 0.00, 2.00 p<0.001, for children and caregivers respectively. CONCLUSION: Night-time honey doses given to children with cough from URTI significantly reduces symptoms and improves children and caregivers sleep compared to Diphenhydramine DPH.

CONTEXTE ET OBJECTIF: La toux due à l'URTI est courante, entraîne une gêne, une perte de sommeil et du stress chez les soignants, conduisant à l'utilisation de médicaments en vente libre inefficaces et potentiellement nocifs. Le miel est rentable et sans danger pour les enfants de plus d'un an. Il est facilement disponible et est un adoucissant potentiellement précieux pour le traitement de la toux infantile. L'étude visait à déterminer l'effet du miel sur la fréquence et la gravité de la toux chez les enfants atteints d'URTI en ambulatoire. MÉTHODES: UNE Essai contrôlé randomisé en simple aveugle impliquant des enfants présentant une toux de l'URTI et participant au GOPC de FMC Keffi. Quatre-vingt-quatre enfants présentant une toux due à l'URTI ont été recrutés, randomisés en deux groupes de 42 et administrés du miel (intervention) et de la diphenhydramine (contrôle) en trois doses consécutives au coucher. Les données sociodémographiques et cliniques, y compris la fréquence, la gravité et l'impact de la toux sur les enfants et les soignants, ont été recueillies à l'aide du questionnaire Pediatric Cough Questionnaire et de l'outil Kingston Caregiver Stress Scale. Les données ont été analysées à l'aide de la version 25 de SPSS. Un p <0,001 était considéré comme statistiquement significatif. RÉSULTATS: La majorité (56,0%) des participants étaient des hommes, avec un âge moyen de 4 ± 1,47 ans. Le score moyen de fréquence de toux pour l'intervention et le contrôle avant et après l'intervention a diminué (5,00 et 0,00 vs 5,00 et 3,00, p <0,001). Le score moyen de gravité de la toux a diminué (4,00 et 0,00 vs 4,00 et 3,00, p <0,001), le fardeau des soignants regroupés après l'intervention a été significativement réduit et le rythme de sommeil s'est amélioré chez les enfants et les soignants. CONCLUSION: Les doses nocturnes de miel administrées aux enfants avec toux par URTI réduisent considérablement les symptômes et améliorent le sommeil des enfants et des soignants par rapport au DPH. Mots clés: Fardeau du soignant; Enfant; Toux; Démulcents; Diphenhydramine; Miel ; Sommeil; Infections des voies respiratoires supérieures.

Diphenhydramine: Time to Move on?

Diphenhydramine is one of the most widely available, longest-used antihistamine medications but has many side effects including sedation and risk of toxicity in overdose including cardiac toxicity. It is frequently inappropriately used when newer, more favorable antihistamine medications are available. Second-generation antihistamines are also widely available and affordable, with many of the same desired effects as diphenhydramine and fewer, if any, of the undesirable side effects. Because of the negative side effects and wide availability of alternative antihistamine medications, it is definitively time to move on from diphenhydramine.

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial.

Importance: Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. Objective: To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. Design, Setting, and Participants: In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Interventions: Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. Main Outcomes and Measures: The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. Results: A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Conclusions and Relevance: Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. Trial Registration: ClinicalTrials.gov Identifier: NCT02061293.

Efficacy of Combination Haloperidol, Lorazepam, and Diphenhydramine vs. Combination Haloperidol and Lorazepam in the Treatment of Acute Agitation: A Multicenter Retrospective Cohort Study.

BACKGROUND: Antipsychotic and sedative combinations are commonly used for treating agitation in the emergency department despite limited evidence regarding their comparative safety and efficacy. OBJECTIVES: To compare the efficacy and safety of combination haloperidol, lorazepam, and diphenhydramine (B52) to combination haloperidol and lorazepam (52) in treating acute agitation. METHODS: This multicenter, retrospective cohort study included adult patients ≥ 18 years of age who received either B52 or 52 at a Banner Health facility between August 2017 and September 2020. Patients were excluded if they had a pre-existing movement disorder or were withdrawing from alcohol. The primary outcome was administration of additional agitation medication(s) within 2 h of B52 or 52. Secondary outcomes included incidence of extrapyramidal symptoms, length of stay, and additional safety measures. RESULTS: There was no difference in administration frequency of additional agitation medication(s) (B52: n = 28 [14%] vs. 52: n = 40 [20%]; p = 0.11). Patients who received 52 were more likely to require an antimuscarinic medication within 2 days (15 vs. 6 patients, p = 0.04). Of the patients who received an antimuscarinic medication, none had documented extrapyramidal symptoms. The 52 group had shorter length of stay (13.8 vs. 17 h; p = 0.03), lower incidence of hypotension (7 vs. 32 patients; p < 0.001), and oxygen desaturation (0 vs. 6 patients; p = 0.01), and fewer physical restraints (53 vs. 86 patients; p = 0.001) compared with the B52 group. CONCLUSIONS: Both the B52 and 52 combinations infrequently required repeat agitation medication; however, the B52 combination resulted in more oxygen desaturation, hypotension, physical restraint use, and longer length of stay.

Efficacy of lipid emulsion therapy in treating cardiotoxicity from diphenhydramine ingestion: a review and analysis of case reports.

INTRODUCTION: Lipid emulsion therapy (LET) has been most thoroughly studied to reverse local anesthetic systemic toxicity (LAST). Case reports suggest that LET can successfully rescue cardiovascular collapse from bupropion, amitriptyline, and propranolol. The efficacy of LET against refractory hypotension and dysrhythmias from diphenhydramine, a commonly ingested lipophilic cardiotoxic agent, is less well described. OBJECTIVE: Summarize the evidence that LET rescues cardiac ion channel blockade (QRS, QTc widening) or hypotension attributable to diphenhydramine overdose. METHODS: We searched MEDLINE, EMBASE, and Google Scholar for English-language full-length case reports of diphenhydramine (DPH) intoxication in patients 17 years of age or older. We extracted data with a PRISMA-compliant protocol, dividing the case reports into two groups, one that received LET and one that did not. We performed a pooled analysis to compare the change in mean arterial pressure (MAP), QRS duration, and QTc duration between the two groups. RESULTS: We identified 23 reports (25 patients). Lipid emulsion therapy (LET) was used in 6 cases because the patient suffered from hypotension refractory to traditional resuscitation. Those who received LET and those who did not were comparable in age, gender, amount ingested, and frequency of seizures. The mean arterial pressure (MAP) decreased by 4.5 ± 11.5 mm Hg in those who did not receive LET compared to an increase in MAP 37 ± 17.5 mm Hg in those who did receive LET. The QRS narrowed by 29 ± 33.9 ms (no LET group) vs 68 ± 49.5 ms (LET group) and QTc by 168.5 ± 126.75 ms (no LET group) vs 134 ± 88 ms (LET group). All values are expressed as median ± interquartile range. One out of the 6 patients who received LET died after withdrawal of care. In the group that did not receive LET 4 out of 19 died and 3 had no outcome reported. DISCUSSION: LET may improve MAP in patients with hypotension refractory to vasopressors due to diphenhydramine toxicity. We found no significant effect of LET on QRS or QTc duration. These results are limited by a small sample size, reporting bias of case reports, incomplete data, and heterogeneity. CONCLUSION: An analysis of pooled case reports suggests that LET may rescue hypotension when other methods have failed in patients with hypotension attributable to diphenhydramine overdose.

Nedocromil sodium and diphenhydramine HCl ameliorate exercise-induced arterial hypoxemia in highly trained athletes.

INTRODUCTION: Exercise-induced arterial hypoxemia (EIAH) has been observed in highly trained endurance athletes during near maximal exercise, which may be influenced by a histamine-mediated inflammatory response at the pulmonary capillary-alveolar membrane. In order to test this hypothesis, we examined whether the mast cell stabilizer nedocromil sodium (NS) and H1 -receptor antagonist diphenhydramine HCL (DH) would ameliorate EIAH and mitigate the drop in arterial oxyhemoglobin saturation (Sa O2 ) during intensive exercise. METHODS: Seven highly trained male cross country runners (age, 21 ± 2 years; V̇O2max , 74.7 ± 3.5 ml·kg-1 ·min-1 ) participated in the study. All subjects completed a maximal exercise treadmill test to exhaustion, followed by three 5-min constant-load exercise bouts at 70%, 80%, and 90% V̇O2max . Prior to testing, subjects received either placebo (PL), NS, or DH. RESULTS: Compared to PL, there was a significant treatment effect on Sa O2 (p < 0.001) for both NS and DH during both constant-load exercise and at V̇O2max . Post hoc tests revealed Sa O2  values, compared to PL, were significantly higher at V̇O2max and during DH trials and higher with NS at constant-load intensities except at 70% (p = 0.13). CONCLUSION: The findings provide further evidence that histamine contributes directly or indirectly to the development of EIAH during intense exercise in highly trained athletes.

Prophylactic administration of diphenhydramine/paracetamol reduced emergence agitation and postoperative pain following maxillofacial surgeries: a randomized controlled trial.

BACKGROUND: Emergence agitation after maxillofacial surgeries is an anxious and problematic complication for the surgeon and anesthesiologist that may lead to self-extubation, haemorrhage, and surgical destruction. In this study, we investigated the effects of preemptive administration of diphenhydramine on emergence agitation and quality of recovery after maxillofacial surgery in adult patients. METHODS: Eighty-five patients undergoing maxillofacial surgery were randomized into two groups. The diphenhydramine group (Group D, n = 40) received diphenhydramine premedication 0.5 mg/kg before anesthesia induction, while the control group (Group C, n = 40) received volume-matched normal saline as a placebo. Before incision, all patients receive 0.1 mg/kg morphine sulfate slowly intravenously within 5 min. Continuous infusion of remifentanil 0.2 µg/kg/h and inhalation of isoflurane was maintained during the anesthesia period. Paracetamol 1 g was infused 15 min before extubation. We evaluated the incidence of agitation during the extubation period after general anesthesia, hemodynamic parameters, and recovery characteristics during the postoperative period. RESULTS: During extubation time, the incidence of emergence agitation was lower in Group D than in Group C (16% vs. 49%, P = 0.041). The time from isoflurane discontinuation to extubation (7.7 min in Group D vs. 6.8 min in Group C, P = 0.082) was not different. Grade of cough during emergence, the severity of pain, analgesic requirements, and hemodynamic changes were lower in group D compared with Group C. CONCLUSIONS: Preemptive administration of diphenhydramine provided smooth emergence from anesthesia. It also improved the quality of recovery after maxillofacial surgery. TRIAL REGISTRATION NUMBER: This study was registered at http://irct.ir (registration number IRCT20130304012695N3).

Assessment of receptor affinities of ophthalmic and systemic agents in dry eye disease.

PURPOSE OF REVIEW: To explore our current understanding of receptor profiles acted upon by medications used to treat dry eye disease (DED). RECENT FINDINGS: Research into histaminic and muscarinic receptor affinities for drugs targeting the ocular surface has not kept up with bench research pertaining to the receptor profile of the ocular surface. These insights are necessary for better evaluation of medications used in DED and other allergic disorders. SUMMARY: At the H1 receptor, Ketotifen (pKa = 9.2), pyrilamine (pKa = 9.0), and epinastine (pKa = 8.0) had the highest affinities, whereas ranitidine (pKa = 4.2) and cimetidine (pKa = 4.9) had the lowest. Ketotifen, a second-generation antihistamine, was found to have a pKa of 6.7 at muscarinic receptors which was higher than that of diphenhydramine (pKa = 6.4), a first-generation antihistamine. Additionally, second-generation antihistamines have higher affinity for H3 receptors, which have been linked to urticaria, compared to first-generation. Azelastine, a second-generation, demonstrated significant affinity (pKa = 7.1) at the H3 receptor compared to all other drugs. Antazoline (pKa = 4.4) and diphenhydramine (pKa = 4.6), both first-generation antihistamines, had the lowest affinities for the H3 receptor. These findings raise questions about the use of antihistamines in the treatment of DED and allergic disorders.

A Case of Massive Diphenhydramine and Naproxen Overdose.

BACKGROUND: Diphenhydramine, a first generation H1 histamine receptor antagonist, is a commonly used nonprescription medication that is used for the treatment of allergy, as a sleep aid, or combined with cough and cold remedies. Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), is used commonly for analgesia. Although most cases of diphenhydramine or naproxen overdose require excellent supportive care only, meticulous attention should be given to cardiovascular and neurologic status. CASE REPORT: A 22-year-old woman presented with altered mental status secondary to intentional ingestion of 240 combination caplets of naproxen sodium 220 mg and diphenhydramine hydrochloride 25 mg. While in the emergency department, she manifested a wide-complex tachycardia in the setting of hypotension that required repeated administration of sodium bicarbonate to overcome the sodium channel blockade caused by diphenhydramine. Aggressive potassium repletion was performed simultaneously. Her clinical course was complicated by status-epilepticus that required intubation. Orogastric lavage was performed, which returned blue pill slurry consistent with the ingested caplets. The patient was extubated on hospital day 2 and transferred to psychiatry thereafter. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In light of recent social media trends, such as the "Benadryl challenge" and its widespread availability, emergency providers should be familiar with diphenhydramine toxicity, especially the life-threatening neurologic consequences and risk of cardiovascular collapse. NSAIDs, such as naproxen, and other nonprescription analgesics are becoming more and more important in light of the current opioid crisis. There should be an emphasis on understanding these medications and their potential implications when taken in overdose.

Retrospective review of diphenhydramine versus diphenhydramine plus glucocorticoid for treatment of uncomplicated allergic reaction in dogs.

OBJECTIVE: To report the outcome of treatment of uncomplicated allergic reactions in dogs with diphenhydramine vs diphenhydramine plus glucocorticoid and to determine the incidence rate of uncomplicated allergic reactions DESIGN: Retrospective study between January 1, 2012 and August 15, 2018. SETTING: Privately owned, 24-hour emergency and specialty referral veterinary hospital. ANIMALS: Eight hundred and eighty cases of dogs treated for uncomplicated allergic reaction with diphenhydramine alone or in combination with a glucocorticoid. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred ninety-nine dogs were treated with diphenhydramine alone, and 581 were treated with diphenhydramine plus Dex SP. There was no difference between the 2 groups for response to initial therapy, need for additional veterinary intervention after discharge, or persistent signs at follow-up. The cumulative incidence of emergency department presentation for uncomplicated allergic reaction in this hospital was 1.2%. CONCLUSIONS: There was no difference in measured outcomes between dogs treated with diphenhydramine alone vs those treated with a glucocorticoid in addition to diphenhydramine in this population of dogs.