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Advances in Therapy Jan 2022Since 1955, the only available H antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered... (Review)
Review
Since 1955, the only available H antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score - 1.6 vs - 1.5, respectively; 95% CI - 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine.
Topics: Administration, Intravenous; Adult; Cetirizine; Diphenhydramine; Histamine H1 Antagonists; Humans; Urticaria
PubMed: 34862952
DOI: 10.1007/s12325-021-01999-x -
PloS One 2022Clinical testing typically relies on invasive blood draws and biopsies. Alternative methods of sample collection are continually being developed to improve patient...
Clinical testing typically relies on invasive blood draws and biopsies. Alternative methods of sample collection are continually being developed to improve patient experience; swabbing the skin is one of the least invasive sampling methods possible. To show that skin swabs in combination with untargeted mass spectrometry (metabolomics) can be used for non-invasive monitoring of an oral drug, we report the kinetics and metabolism of diphenhydramine in healthy volunteers (n = 10) over the course of 24 hours in blood and three regions of the skin. Diphenhydramine and its metabolites were observed on the skin after peak plasma levels, varying by compound and skin location, and is an illustrative example of how systemically administered molecules can be detected on the skin surface. The observation of diphenhydramine directly from the skin supports the hypothesis that both parent drug and metabolites can be qualitatively measured from a simple non-invasive swab of the skin surface. The mechanism of the drug and metabolites pathway to the skin's surface remains unknown.
Topics: Diphenhydramine; Humans; Mass Spectrometry; Metabolomics; Skin
PubMed: 35881585
DOI: 10.1371/journal.pone.0271794 -
Cardiovascular Toxicology Sep 2022Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies...
Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as "Known Risk of TdP" but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the "Known Risk" substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common "Known Risk" substances were citalopram, escitalopram and cocaine. Although not in the "Known Risk" category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2-55.8) and methadone (OR 7.1, 95% CI 2.1-23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of "Known Risk of TdP" QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias.
Topics: Amitriptyline; Arrhythmias, Cardiac; Diphenhydramine; Electrocardiography; Flecainide; Humans; Long QT Syndrome; Methadone; Mirtazapine; Poison Control Centers; Retrospective Studies; Risk Factors; Tachycardia, Ventricular; Torsades de Pointes; Trazodone; Ventricular Fibrillation
PubMed: 35930218
DOI: 10.1007/s12012-022-09764-4 -
Cell Calcium Sep 2020Diphenhydramine (DPH) has been broadly used to treat allergy. When used as a topical medicine, DPH temporarily relieves itching and pain. Although transient receptor...
Diphenhydramine (DPH) has been broadly used to treat allergy. When used as a topical medicine, DPH temporarily relieves itching and pain. Although transient receptor potential type A1 (TRPA1) channel is known to play roles in both acute and chronic itch and pain, whether DPH affects the activities of TRPA1 remains unclear. Using whole-cell patch clamp recordings, we demonstrated that DPH modulates the voltage-dependence of TRPA1. When co-applied with a TRPA1 agonist, DPH significantly enhanced the inward currents while suppressing the outward currents of TRPA1, converting the channel from outwardly rectifying to inwardly rectifying. This effect of DPH occurred no matter TRPA1 was activated by an electrophilic or non-electrophilic agonist and for both mouse and human TRPA1. The modulation of TRPA1 by DPH was maintained in the L906C mutant, which by itself also causes inward rectification of TRPA1, indicating that additional acting sites are present for the modulation of TRPA1 currents by DPH. Our recordings also revealed that DPH partially blocked capsaicin evoked TRPV1 currents. These data suggest that DPH may exert its therapeutic effects on itch and pain, through modulation of TRPA1 in a voltage-dependent fashion.
Topics: Animals; Calcium; Diphenhydramine; Electric Conductivity; Electricity; Extracellular Space; HEK293 Cells; Humans; Ion Channel Gating; Ions; Isothiocyanates; Magnesium; Membrane Potentials; Mice; Mutation; TRPA1 Cation Channel
PubMed: 32634675
DOI: 10.1016/j.ceca.2020.102245 -
Scientific Reports Aug 2023Orphenadrine (ORP), dimenhydrinate (DMN), and cinnarizine (CNN) were investigated using green-sensitive spectrofluorometric methods. Method, I used for determination of...
Orphenadrine (ORP), dimenhydrinate (DMN), and cinnarizine (CNN) were investigated using green-sensitive spectrofluorometric methods. Method, I used for determination of DMN in 0.1 M hydrochloric acid (HCl) and 1.0% sodium dodecyl sulphate (SDS) at 286 nm after λ 222 nm, while for determination of ORP in 1.0% w/v SDS involves measuring the fluorescence at 285 nm after λ 220 nm. For DMN and ORP, the detection and quantitation limits were 2.99 and 4.71 and 9.08 and 14.29 ng/mL, respectively. The ranges of DMN and ORP were 0.10-1.0 and 0.04-0.5 µg/mL, respectively, in micellar aqueous solution. Method II, the derivative intensities of DMN and CNN were measured at a fixed of different wavelength between the excitation and the emission wavelengths (Δλ) = 60 nm at 282 and 322 nm, at the zero crossing of each other, respectively. The detection and quantitation limits for DMN and CNN were 1.77 and 0.88 ng/mL and 5.36 and 2.65 ng/mL, correspondingly, through the entire range of 0.1-1.0 µg/mL for DMN and CNN. The linearity was perfectly determined through the higher values of the correlation coefficient ranging from 0.9997 to 0.9999 for both direct and synchronous methods. The precision of the proposed methods was also confirmed via the lower values of the standard deviation which ranged from 0.39 to 1.11. The technique was expanded to analyze this mixture in combined tablets and laboratory-prepared mixtures. The method validation was done depending on the international conference on harmonization (ICH) recommendations. An analysis of the statistical data revealed a high agreement between the proposed data and the comparison methodology. Three different assessment methods demonstrated the greenness of the technique.
Topics: Cinnarizine; Dimenhydrinate; Hydrochloric Acid; Laboratories; Orphenadrine; Spectrometry, Fluorescence
PubMed: 37599333
DOI: 10.1038/s41598-023-40559-x -
The Cochrane Database of Systematic... Nov 2015Nausea and vomiting are common symptoms in patients with terminal, incurable illnesses. Both nausea and vomiting can be distressing. Haloperidol is commonly prescribed... (Review)
Review
BACKGROUND
Nausea and vomiting are common symptoms in patients with terminal, incurable illnesses. Both nausea and vomiting can be distressing. Haloperidol is commonly prescribed to relieve these symptoms. This is an updated version of the original Cochrane review published in Issue 2, 2009, of Haloperidol for the treatment of nausea and vomiting in palliative care patients.
OBJECTIVES
To evaluate the efficacy and adverse events associated with the use of haloperidol for the treatment of nausea and vomiting in palliative care patients.
SEARCH METHODS
For this updated review, we performed updated searches of CENTRAL, EMBASE and MEDLINE in November 2013 and in November 2014. We searched controlled trials registers in March 2015 to identify any ongoing or unpublished trials. We imposed no language restrictions. For the original review, we performed database searching in August 2007, including CENTRAL, MEDLINE, EMBASE, CINAHL and AMED, using relevant search terms and synonyms. Handsearching complemented the electronic searches (using reference lists of included studies, relevant chapters and review articles) for the original review.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) of haloperidol for the treatment of nausea or vomiting, or both, in any setting, for inclusion. The studies had to be conducted with adults receiving palliative care or suffering from an incurable progressive medical condition. We excluded studies where nausea or vomiting, or both, were thought to be secondary to pregnancy or surgery.
DATA COLLECTION AND ANALYSIS
We imported records from each of the electronic databases into a bibliographic package and merged them into a core database where we inspected titles, keywords and abstracts for relevance. If it was not possible to accept or reject an abstract with certainty, we obtained the full text of the article for further evaluation. The two review authors independently assessed studies in accordance with the inclusion criteria. There were no differences in opinion between the authors with regard to the assessment of studies.
MAIN RESULTS
We considered 27 studies from the 2007 search. In this update we considered a further 38 studies from the 2013 search, and two in the 2014 search. We identified one RCT of moderate quality with low risk of bias overall which met the inclusion criteria for this update, comparing ABH (Ativan®, Benadryl®, Haldol®) gel, applied to the wrist, with placebo for the relief of nausea in 22 participants. ABH gel includes haloperidol as well as diphenhydramine and lorazepam. The gel was not significantly better than placebo in this small study; however haloperidol is reported not to be absorbed significantly when applied topically, therefore the trial does not address the issue of whether haloperidol is effective or well-tolerated when administered by other routes (e.g. by mouth, subcutaneously or intravenously). We identified one ongoing trial of haloperidol for the management of nausea and vomiting in patients with cancer, with initial results published in a conference abstract suggesting that haloperidol is effective for 65% of patients. The trial had not been fully published at the time of our review. A further trial has opened, comparing oral haloperidol with oral methotrimeprazine (levomepromazine) for patients with cancer and nausea unrelated to their treatment, which we aim to include in the next review update.
AUTHORS' CONCLUSIONS
Since the last version of this review, we found one new study for inclusion but the conclusion remains unchanged. There is incomplete evidence from published RCTs to determine the effectiveness of haloperidol for nausea and vomiting in palliative care. Other than the trial of ABH gel vs placebo, we did not identify any fully published RCTs exploring the effectiveness of haloperidol for nausea and vomiting in palliative care patients for this update, but two trials are underway.
Topics: Antiemetics; Diphenhydramine; Gels; Haloperidol; Humans; Lorazepam; Nausea; Palliative Care; Randomized Controlled Trials as Topic; Vomiting
PubMed: 26524474
DOI: 10.1002/14651858.CD006271.pub3 -
JAMA Apr 2019
Topics: Antacids; Diphenhydramine; Doxepin; Humans; Lidocaine; Mouthwashes; Pain; Stomatitis
PubMed: 30990535
DOI: 10.1001/jama.2019.3269 -
BMJ Case Reports Sep 2020SARS-CoV-2, the virus responsible for COVID-19, binds to the ACE2 receptors. ACE2 is thought to counterbalance ACE in the renin-angiotensin system. While presently it is...
SARS-CoV-2, the virus responsible for COVID-19, binds to the ACE2 receptors. ACE2 is thought to counterbalance ACE in the renin-angiotensin system. While presently it is advised that patients should continue to use ACE inhibitors or angiotensin receptor blockers, questions still remain as to whether adverse effects are potentiated by the virus. Here, we report a case of a 57-year-old man, unknowingly with COVID-19, who presented to the emergency department with tongue swelling, shortness of breath and difficulty in speaking following 4 months taking benazepril, an ACE inhibitor. Finally, we also describe possible pathways that exist for SARS-CoV-2 to interact with the mechanism behind angioedema.
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Anti-Allergic Agents; Benzazepines; Betacoronavirus; COVID-19; Coronavirus Infections; Diagnosis, Differential; Diphenhydramine; Famotidine; Histamine H2 Antagonists; Humans; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tranexamic Acid
PubMed: 32912894
DOI: 10.1136/bcr-2020-237888 -
Obesity Surgery Oct 2021Postoperative nausea and vomiting (PONV) and pain following bariatric surgery are problematic and affect the outcome of patients. Intraoperative multimodal antiemetic... (Randomized Controlled Trial)
Randomized Controlled Trial
Prophylactic Administration of Diphenhydramine/Acetaminophen and Ondansetron Reduced Postoperative Nausea and Vomiting and Pain Following Laparoscopic Sleeve Gastrectomy: a Randomized Controlled Trial.
PURPOSE
Postoperative nausea and vomiting (PONV) and pain following bariatric surgery are problematic and affect the outcome of patients. Intraoperative multimodal antiemetic prophylaxis is essential to improve postoperative outcomes. This study investigated the effect of adding diphenhydramine to acetaminophen and ondansetron in reducing postoperative nausea and vomiting and pain following laparoscopic sleeve gastrectomy (LSG).
MATERIALS AND METHODS
Eighty-two patients scheduled for LSG were assigned to receive a single preinduction dose of diphenhydramine 0.4 mg/kg VI (D group) in addition to acetaminophen 1g and ondansetron 4 mg IV at the end of surgery and just acetaminophen 1 g and ondansetron 4 mg IV (C group) in a randomized, double-blind trial. PONV was assessed in recovery and 24 hours after surgery in the ward. Postoperative pain, analgesic requirements, and patients' level of sedation were also assessed.
RESULTS
The PONV rates in the recovery of the D group and the C group were 30% and 56% (P = .001). It also had a more significant reduction in the D group than in the C group in the first 24 h after surgery (40% vs. 66%). The severity of pain score and level of sedation and analgesic requirements was significantly reduced in this period in the D group.
CONCLUSION
Prophylactic diphenhydramine 0.4 mg/kg at the induction of general anesthesia in combination with acetaminophen 1 g and ondansetron 4 mg at the end of surgery reduced the incidence of PONV and postoperative severity of pain in laparoscopic sleeve gastrectomy.
Topics: Acetaminophen; Antiemetics; Diphenhydramine; Double-Blind Method; Gastrectomy; Humans; Laparoscopy; Obesity, Morbid; Ondansetron; Pain, Postoperative; Postoperative Nausea and Vomiting
PubMed: 34313917
DOI: 10.1007/s11695-021-05589-2 -
Journal of the National Comprehensive... Dec 2018
Topics: Administration, Intravenous; Antineoplastic Agents; Diphenhydramine; Drug Industry; Drugs, Generic; Humans; Medical Oncology; Neoplasms; Patents as Topic
PubMed: 30545986
DOI: 10.6004/jnccn.2018.0090