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The Cochrane Database of Systematic... Jun 2010Allergic and febrile non-haemolytic transfusion reactions (NHTRs) are the two most common forms of transfusion reaction. Pretransfusion medication with anti-inflammatory... (Review)
Review
BACKGROUND
Allergic and febrile non-haemolytic transfusion reactions (NHTRs) are the two most common forms of transfusion reaction. Pretransfusion medication with anti-inflammatory drugs is used in NHTR prevention, however its efficacy and safety remains unclear.
OBJECTIVES
To assess the clinical effects and safety of pharmacological interventions for preventing NHTR in patients with and without a history of transfusion reactions.
SEARCH STRATEGY
The search strategy included The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4, 2008), Cochrane Injuries Group's Specialised Register (December 17, 2008), MEDLINE (1950 to November (week 3) 2008), EMBASE (1988 to November (week 3) 2008), LILACS (1982 to January 12, 2009), CINAHL (1982 to December 2008), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED): 1970 to December 2008). There was no language restriction.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing the effectiveness of interventions for the prevention of NHTR.
DATA COLLECTION AND ANALYSIS
Authors independently selected studies, assessed the risks of bias and extracted data. Relative risks (RR) were estimated in RCTs with parallel design (PD). Odds ratio (OR) was estimated for one RCT with crossover design (CD). No meta-analysis was attempted due to differences in the pharmacotherapy of pre-transfusion medication and methodology between the studies; a per-protocol analysis was used.
MAIN RESULTS
This review includes three RCTs (two PD and one CD). The PD-RCTs employed disparate units of randomisation (UofR); patient or transfusion, while the CD-RCT applied the patient as the UofR. The PD-RCTs administered leukodepleted blood products. Both PD-RCTs compared acetaminophen plus diphenhydramine (ApD) at different regimens with placebo, while the CD-RCT contrasted hydrocortisone pharmacotherapy with diphenhydramine. Both PD-RCTs found no statistically significant difference in allergic reactions (RR 0.13, 95% confidence interval (CI) 0.01 to 2.39, RR 1.46, 95% CI 0.78 to 2.73) and febrile reactions (RR 0.52, 95% CI 0.22 to 1.26). The CD-RCT found a statistically significant difference in the odds of febrile reactions (OR 2.38, 95% CI 1.07 to 5.27). The trials did not report anaphylactic reactions, deaths related to transfusion reactions or other adverse events.
AUTHORS' CONCLUSIONS
None of the three studies found that medication prior to transfusion reduces NHTR. This applied regardless of the patient's history of NHTR and the use of leukodepleted blood products in the transfusion. However, this conclusion is based on three trials of moderate to low quality. A better-powered RCT is necessary to evaluate the role of pretransfusion medication in the prevention of NHTR. Inclusion criteria should be restricted to patients at high risk of developing NHTR, with no restriction by age, history of transfusion reactions and type of blood products (leukodepleted or not).
Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Diphenhydramine; Fever; Histamine H1 Antagonists; Humans; Hydrocortisone; Hypersensitivity; Premedication; Randomized Controlled Trials as Topic; Transfusion Reaction
PubMed: 20556779
DOI: 10.1002/14651858.CD007539.pub2 -
Cancer May 2003Oxaliplatin is a third-generation platinum analog that is used to treat a variety of solid tumors, particularly colorectal carcinoma. Patients may develop... (Review)
Review
BACKGROUND
Oxaliplatin is a third-generation platinum analog that is used to treat a variety of solid tumors, particularly colorectal carcinoma. Patients may develop hypersensitivity reactions, although this complication occurs infrequently.
METHODS
Three patients developed hypersensitivity reactions to oxaliplatin while undergoing treatment on a Phase I trial of oxaliplatin and capecitabine. An Entrez PUBMED search was performed to identify other cases.
RESULTS
Two patients experienced the abrupt onset of erythema alone or with pruritus during the 9th and 11th infusions of oxaliplatin, whereas the other patient developed fever and mild dyspnea a few hours after the 9th oxaliplatin infusion. All 3 patients were rechallenged successfully for at least 1 additional oxaliplatin infusion by using oral dexamethasone, 20 mg orally, 6 and 12 hours before the administration of oxaliplatin and by administering intravenously 125 mg of solumedrol, 50 mg of diphenhydramine, and 50 mg of cimetidine 30 minutes before oxaliplatin. The literature review suggests two distinct patterns of reactions: classic hypersensitivity (as experienced by the first two patients) and idiosyncratic reactions (as experienced by the third patient).
CONCLUSIONS
Patients who develop mild to moderate hypersensitivity to oxaliplatin may be pretreated with steroids and antagonists of Type 1 and 2 histamine receptors, whereas patients who develop severe reactions are unlikely to tolerate further therapy.
Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents; Antiemetics; Antineoplastic Agents; Cimetidine; Dexamethasone; Diphenhydramine; Drug Hypersensitivity; Dyspnea; Erythema; Female; Fever; Histamine H2 Antagonists; Humans; Male; Methylprednisolone Hemisuccinate; Middle Aged; Neoplasms; Organoplatinum Compounds; Oxaliplatin
PubMed: 12712487
DOI: 10.1002/cncr.11379 -
Journal of Medical Toxicology :... Sep 2018Diphenhydramine is a widely used first-generation histamine (H) antagonist that can be obtained without prescription in many countries. Massive ingestions can result in...
INTRODUCTION
Diphenhydramine is a widely used first-generation histamine (H) antagonist that can be obtained without prescription in many countries. Massive ingestions can result in severe toxicity and even death. We describe a case of diphenhydramine overdose leading to cardiac arrest, cardiopulmonary resuscitation (CPR), and extracorporeal membrane oxygenation (ECMO) cannulation for refractory ventricular fibrillation, a process we refer to as extracorporeal cardiopulmonary resuscitation (ECPR).
CASE REPORT
Responding to a call for altered mental status, emergency medical service (EMS) personnel found an unconscious and seizing 17-year-old male. He had reportedly developed generalized tonic-clonic seizures and dysrhythmias after ingesting approximately 800 25-mg diphenhydramine tablets. He was transferred to our pediatric intensive care unit (PICU) after stabilization at a local emergency center. After approximately 7 hours of clinical stability and normalization of cardiac rhythm, electrolytes, and acidosis, he developed renewed seizure activity and accelerated ventricular rhythm leading to hemodynamic collapse and cardiac arrest. He was cannulated for veno-arterial extracorporeal membrane oxygenation (VAECMO) with CPR in progress. A pharmacobezoar located in his stomach was presumed to be the cause of his biphasic clinical deterioration. After 5 days, the patient was successfully weaned from ECMO support. Ten days later, his convalescence continued in the step-down unit and was discharged with good functional outcome.
DISCUSSION
Significant ingestion of anticholinergic substances is often fatal. This case describes a favorable outcome after ECPR and aggressive supportive management following a large intentional overdose of diphenhydramine.
Topics: Adolescent; Bezoars; Cardiopulmonary Resuscitation; Critical Care; Diphenhydramine; Electrocardiography; Epilepsy, Tonic-Clonic; Extracorporeal Membrane Oxygenation; Heart Arrest; Histamine H1 Antagonists; Humans; Male; Treatment Outcome
PubMed: 29956117
DOI: 10.1007/s13181-018-0672-6 -
The Journal of Dermatological Treatment Dec 2024Though Janus kinase inhibitors such as upadacitinib rapidly relieve itch in atopic dermatitis (AD) patients, how early itch relief impacts later skin clearance is not...
BACKGROUND
Though Janus kinase inhibitors such as upadacitinib rapidly relieve itch in atopic dermatitis (AD) patients, how early itch relief impacts later skin clearance is not examined.
OBJECTIVES
This study aims to determine if early itch relief by upadacitinib could predict complete skin clearance in later phases.
METHODS
This retrospective study involved 105 patients with moderate-to-severe AD treated with upadacitinib 15 mg/day. Eczema area and severity index (EASI), atopic dermatitis control tool, and achievement rate of EASI 100 were evaluated at weeks 4, 12, and 24. The threshold of early peak pruritus-numerical rating scale (PP-NRS) predicting later skin clearance was assessed by area under the receiver-operating characteristic curve, and predictors for EASI 100 achievement were determined by logistic regression analysis.
RESULTS
The rate of achieving EASI 100 at week 24 was extremely higher in patients who achieved week 2 PP-NRS ≤ 1 (42.9%) than in non-achievers (1.4%). The logistic regression analysis showed that the achievement of week 2 PP-NRS ≤ 1 and low body mass index were associated with achievement of EASI 100 at weeks 12 and 24.
CONCLUSIONS
The achievement of week 2 PP-NRS ≤ 1 may predict later skin clearance in upadacitinib treatment.
Topics: Humans; Dermatitis, Atopic; Retrospective Studies; Skin; Heterocyclic Compounds, 3-Ring; Pruritus; Diphenhydramine; Severity of Illness Index; Treatment Outcome; Double-Blind Method
PubMed: 38073560
DOI: 10.1080/09546634.2023.2291317 -
Yakugaku Zasshi : Journal of the... Mar 2018Diphenhydramine (DP), an antihistaminic agent, may become colored and daker or more fluorescent during storage. Herein, we spectroscopically examined the causes of...
Diphenhydramine (DP), an antihistaminic agent, may become colored and daker or more fluorescent during storage. Herein, we spectroscopically examined the causes of this phenomenon under various DP storage conditions and durations. The infrared vibration-rotation spectrum shows multiple Gauche (G)-type conformers with different intramolecular n→π interaction strengths. The splitting pattern of the dimethylamino group protons in the H-NMR spectrum indicates that DP is mainly in the G-type with a small portion in the Trans (T)-type. The correlation between the red-shifted peak intensity in the UV•VIS absorbance spectrum and the coloring progression indicates a decreased intramolecular n→π interaction of the G-type under elevated temperature during storage. Enhanced fluorescence detected in the Excitation•Fluorescence spectrum demonstrates G-type (quenching) to T-type (fluorescent) conformation conversion, which is due to activated internal rotation of the dimethylamino group under elevated storage temperature and electronic excitation in the phenyl groups under light irradiation during storage. A signal detected in the ESR spectrum corresponds to the G-type charge transfer (CT) structure wherein part of the nonbonding electron pair on the N atom is intramolecularly redistributed to the phenyl groups. The CT structure presents the G-type quenching characteristics, whereas weak CT bonding corresponds to coloring. The results indicate that the quenching G-type is converted to T-type by heat or light to become color faded and bright with enhanced fluorescence and that T-type is reverted to G-type after storage under cool and dark conditions or by vacuum distillation to lose fluorescence.
Topics: Color; Diphenhydramine; Drug Stability; Drug Storage; Electron Spin Resonance Spectroscopy; Fluorescence; Histamine Antagonists; Isomerism; Light; Magnetic Resonance Spectroscopy; Molecular Conformation; Rotation; Spectrometry, Fluorescence; Spectrophotometry, Infrared; Spectrum Analysis; Temperature; Vibration
PubMed: 29279438
DOI: 10.1248/yakushi.17-00175 -
Neurology May 2021To determine whether IV metoclopramide 20 mg + diphenhydramine 25 mg (M + D) was more efficacious than IV placebo for acute moderate or severe posttraumatic headache in... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To determine whether IV metoclopramide 20 mg + diphenhydramine 25 mg (M + D) was more efficacious than IV placebo for acute moderate or severe posttraumatic headache in the emergency room.
METHODS
We conducted this randomized, double-blind, placebo-controlled, parallel-group study in 2 urban emergency departments (EDs). Participants who experienced head trauma and presented to our EDs within 10 days with a headache fulfilling criteria for acute posttraumatic headache were included. We randomized participants in a 1:1 ratio to M + D or placebo. Participants, caregivers, and outcome assessors were blinded to assignment. The primary outcome was improvement in pain on a scale of 0 to 10 between baseline and 1 hour after treatment.
RESULTS
This study was completed between August 2017 and March 2020. We screened 414 patients for participation and randomized 160: 81 to M + D and 79 to placebo. Baseline characteristics were comparable between the groups. All enrolled participants provided primary outcome data. Patients receiving placebo reported mean improvement of 3.8 (SD 2.6), while those receiving M + D improved by 5.2 (SD 2.3), for a difference favoring metoclopramide of 1.4 (95% confidence interval [CI] 0.7-2.2, < 0.01). Adverse events were reported by 35 of 81 (43%) patients who received metoclopramide and 22 of 79 (28%) of patients who received placebo (95% CI 1-30 for difference of 15%, = 0.04).
CONCLUSION
M + D was more efficacious than placebo with regard to relief of posttraumatic headache in the ED.
TRIAL REGISTRATION INFORMATION
ClinicalTrials.gov Identifier: NCT03220958.
CLASSIFICATION OF EVIDENCE
This study provides Class I evidence that for patients with acute moderate or severe posttraumatic headache, IV M + D significantly improved pain compared to placebo.
Topics: Acute Pain; Administration, Intravenous; Adult; Diphenhydramine; Dopamine D2 Receptor Antagonists; Double-Blind Method; Drug Therapy, Combination; Emergency Service, Hospital; Female; Humans; Hypnotics and Sedatives; Male; Metoclopramide; Middle Aged; Pain Measurement; Post-Traumatic Headache
PubMed: 33762421
DOI: 10.1212/WNL.0000000000011822 -
British Journal of Clinical Pharmacology May 2017Centrally-acting acutely anxiolytic drugs, such as benzodiazepines, barbiturates and gabapentinoids, affect various central nervous system (CNS) functions, which... (Comparative Study)
Comparative Study Randomized Controlled Trial
AIM
Centrally-acting acutely anxiolytic drugs, such as benzodiazepines, barbiturates and gabapentinoids, affect various central nervous system (CNS) functions, which reflects not only their anxiolytic effects but also neuropsychological side-effects. To validate the pharmacodynamic biomarkers for GABA-ergic anxiolytics, this study determined the pharmacodynamics of two anxiolytics and a nonanxiolytic control, and linked them to their anxiolytic and sedative effects, during an anxiety-challenge study day.
METHODS
Twenty healthy volunteers were randomized in this placebo-controlled, double-blind, four-way cross-over study with single-dose alprazolam (1 mg), diphenhydramine (50 mg), pregabalin (200 mg) or placebo. The Neurocart was used between repeated fear-potentiated startle assessments. Thus, the potential influence of anxiety on CNS pharmacodynamic markers could be examined.
RESULTS
Compared to placebo, VAS increased with alprazolam (2.0 mm) and pregabalin (2.5 mm) but not with diphenhydramine. Saccadic peak velocity (SPV) declined after alprazolam (-57 ° s ) and pregabalin (-28 ° s ), more than with diphenhydramine (-14 ° s ); so did smooth pursuit. The average responses of SPV and smooth pursuit were significantly correlated with the drug-induced increases in VAS . The SPV-relative responses of VAS , body-sway and adaptive-tracking also differed among alprazolam, pregabalin and diphenhydramine.
CONCLUSIONS
Compared with the antihistaminergic sedative diphenhydramine, alprazolam and pregabalin caused larger SPV reduction, which was correlated with simultaneous improvement of subjective calmness, during a study day in which anxiety was stimulated repeatedly. The different effect profiles of the three drugs are in line with their pharmacological distinctions. These findings corroborate the profiling of CNS effects to demonstrate pharmacological selectivity, and further support SPV as biomarker for anxiolysis involving GABA-ergic neurons. The study also supports the use of prolonged mild threat to demonstrate anxiolytic effects in healthy volunteers.
Topics: Adolescent; Adult; Alprazolam; Anti-Anxiety Agents; Anxiety; Biomarkers; Cross-Over Studies; Diphenhydramine; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Male; Pregabalin; Reflex, Startle; Saccades; Young Adult; gamma-Aminobutyric Acid
PubMed: 27922194
DOI: 10.1111/bcp.13204 -
Physiological Reports Oct 2020Reports of the stimulated release of extracellular vesicles (EVs) are few, and the mechanisms incompletely understood. To our knowledge, the possibility that the...
Reports of the stimulated release of extracellular vesicles (EVs) are few, and the mechanisms incompletely understood. To our knowledge, the possibility that the activation of any one of the multitudes of G-protein-coupled receptors (GPCRs) expressed by a single cell-type might increase EV release has not been explored. Recently, we identified the expression of cholecystokinin (CCK), gastrin, gastrin/cholecystokinin types A and/or B receptors (CCKAR and/or -BR), and the bitter taste receptor, TAS2R14 in the human and mouse placenta. specifically, trophoblast. These GPCR(s) were also expressed in four different human trophoblast cell lines. The current objective was to employ two of these cell lines-JAR choriocarcinoma cells and HTR-8/SVneo cells derived from first-trimester human villous trophoblast-to investigate whether CCK, TAS2R14 agonists, and other GPCR ligands would each augment EV release. EVs were isolated from the cell-culture medium by filtration and ultracentrifugation. The preparations were enriched in small EVs (<200 nm) as determined by syntenin western blot before and after sucrose gradient purification, phycoerythrin (PE)-ADAM10 antibody labeling, and electron microscopy. Activation of TAS2R14, CCKBR, cholinergic muscarinic 1 & 3, and angiotensin II receptors, each increased EV release by 4.91-, 2.79-, 1.87-, and 3.11-fold, respectively (all p < .05 versus vehicle controls), without significantly changing EV diameter. A progressive increase of EV concentration in conditioned medium was observed over 24 hr consistent with the release of preformed EVs and de novo biogenesis. Compared to receptor-mediated stimulation, EV release by the calcium ionophore, A23187, was less robust (1.63-fold, p = .08). Diphenhydramine, a TAS2R14 agonist, enhanced EV release in JAR cells at a concentration 10-fold below that required to increase intracellular calcium. CCK activation of HTR-8/SVneo cells, which did not raise intracellular calcium, increased EV release by 2.06-fold (p < .05). Taken together, these results suggested that other signaling pathways may underlie receptor-stimulated EV release besides, or in addition to, calcium. To our knowledge, the finding that the activation of multiple GPCRs can stimulate EV release from a single cell-type is unprecedented and engenders a novel thesis that each receptor may orchestrate intercellular communication through the release of EVs containing a subset of unique cargo, thus mobilizing a specific integrated physiological response by a network of neighboring and distant cells.
Topics: Calcium; Cell Line, Tumor; Cholecystokinin; Diphenhydramine; Extracellular Vesicles; Flufenamic Acid; Humans; Receptors, Cholecystokinin; Receptors, G-Protein-Coupled; Trophoblasts
PubMed: 33080118
DOI: 10.14814/phy2.14592 -
Psychosomatics Jul 1986
Topics: Adult; Diphenhydramine; Fluphenazine; Humans; Male; Priapism
PubMed: 3737847
DOI: 10.1016/S0033-3182(86)72666-2 -
Journal of the American Veterinary... Jul 2016OBJECTIVE To characterize the signalment, dose response, and clinical signs of diphenhydramine toxicosis in dogs. DESIGN Retrospective case series. ANIMALS 621 dogs with...
OBJECTIVE To characterize the signalment, dose response, and clinical signs of diphenhydramine toxicosis in dogs. DESIGN Retrospective case series. ANIMALS 621 dogs with diphenhydramine exposure. PROCEDURES The electronic medical record database for an animal poison control center was reviewed from January 2008 through December 2013 to identify dogs that had ingested or been injected with diphenhydramine. Information extracted from the records and evaluated included the signalment, clinical signs observed, and estimated exposure dose of diphenhydramine. Clinical signs were categorized as none, mild, moderate, and severe. RESULTS The mean ± SEM age of dogs was 3.6 ± 0.1 years (range, 0.1 to 16 years). Diphenhydramine exposure was by ingestion for 581 (93.6%) dogs and injection for 40 (6.4%) dogs. Only 146 (23.5%) dogs developed ≥ 1 clinical signs of toxicosis, the most common of which were associated with the nervous (lethargy, hyperactivity, agitation, hyperthermia, ataxia, tremors, and fasciculations) or cardiovascular (tachycardia) systems, and 3 dogs died. Although the presence and extent of clinical signs varied greatly among dogs, the exposure dose of diphenhydramine was positively associated with the severity of clinical signs in a dose-dependent manner regardless of the route of exposure (ingestion or injection). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs exposed to diphenhydramine developed clinical signs of toxicosis fairly infrequently, and those clinical signs were generally mild and primarily affected the neurologic and cardiovascular systems. Supportive treatment for diphenhydramine toxicosis should be administered on the basis of the clinical signs observed.
Topics: Animals; Anti-Allergic Agents; Diphenhydramine; Dog Diseases; Dogs; Female; Illinois; Male; Poison Control Centers; Poisoning; Retrospective Studies; Severity of Illness Index
PubMed: 27308885
DOI: 10.2460/javma.249.1.77