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1.
Pediatrics ; 148(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34607934

RESUMO

BACKGROUND AND OBJECTIVES: In 2008, over-the-counter cough and cold medications (CCMs) underwent labeling changes in response to safety concerns, including fatalities, reported in children exposed to CCMs. The objective of this study is to describe fatalities associated with exposures to CCMs in children <12 years old that were detected by a safety surveillance system from 2008 to 2016. METHODS: Fatalities in children <12 years old that occurred between 2008 and 2016 associated with oral exposure to one or more CCMs were identified by the Pediatric Cough and Cold Safety Surveillance System. An expert panel reviewed all cases to determine the causal relationship between the exposure and death, if the intent of exposure was therapeutic, and if the dose was supratherapeutic. Other contributing factors related to the child's death were also identified as part of a root cause analysis. RESULTS: Of the 180 eligible fatalities captured during the study period, 40 were judged by the expert panel to be either related or potentially related to the CCM. Of these, the majority (n = 24; 60.0%) occurred in children <2 years old and involved nontherapeutic intent (n = 22; 55.0%). The most frequently involved index ingredient was diphenhydramine (n = 28; 70.0%). In 6 cases (n = 6; 15.0%), the CCM was administered to murder the child. In another 7 cases (n = 7; 17.5%), death followed the intentional use of the CCM to sedate the child. CONCLUSIONS: Pediatric fatalities associated with CCMs occurred primarily in young children after deliberate medication administration with nontherapeutic intent by a caregiver.


Assuntos
Antitussígenos/envenenamento , Medicamentos sem Prescrição/envenenamento , Antitussígenos/administração & dosagem , Bromofeniramina/envenenamento , Criança , Pré-Escolar , Clorfeniramina/envenenamento , Dextrometorfano/envenenamento , Difenidramina/administração & dosagem , Difenidramina/envenenamento , Doxilamina/envenenamento , Rotulagem de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Feminino , Guaifenesina/envenenamento , Homicídio/estatística & dados numéricos , Humanos , Lactente , Masculino , Medicamentos sem Prescrição/administração & dosagem , Fenilefrina/envenenamento , Pseudoefedrina/envenenamento
2.
J Infus Nurs ; 44(6): 315-322, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34555839

RESUMO

Pretreatment with antihistamines for the prevention of hypersensitivity infusion reactions is recommended for certain biologics and chemotherapies. Cetirizine is the first injectable second-generation antihistamine recently approved for acute urticaria. A randomized, exploratory phase 2 study evaluated intravenous (IV) cetirizine 10 mg versus IV diphenhydramine 50 mg as pretreatment in patients receiving an anti-CD20 agent or paclitaxel. In the overall population (N = 34) and an elderly subgroup (n = 21), IV cetirizine was as effective as IV diphenhydramine in preventing infusion reactions (primary outcome) and associated with less sedation at all time points, a shorter infusion center stay, and fewer treatment-related adverse events.


Assuntos
Cetirizina , Urticária , Administração Intravenosa , Idoso , Cetirizina/efeitos adversos , Difenidramina/uso terapêutico , Humanos , Paclitaxel/efeitos adversos , Urticária/tratamento farmacológico
3.
Biochem Pharmacol ; 192: 114751, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34464621

RESUMO

BACKGROUND: Although psychostimulants apparently do cross the BBB, it is poorly understood how these hydrophilic and positively charged molecules can pass the blood-brain barrier (BBB). That may be mediated by a genetically still uncharacterized H+/OC antiporter with high activity at the BBB. METHODS: We studied the uptake of 16 psychostimulants and hallucinogens with hCMEC/D3 cells using the prototypic inhibitor imipramine (cis-inhibition), exchange transport with diphenhydramine and clonidine (trans-stimulation), proton dependency of the uptake, and we characterized the concentration-dependent uptake. RESULTS: Cell uptake of methylenedioxyamphetamines, amphetamines and dimethyltryptamine (DMT) were strongly inhibited (to about 10% of the controls) by imipramine and diphenhydramine, whereas uptake of cathine was only weakly inhibited and mescaline not significantly. Amphetamine, methylamphetamine, para-Methoxy-N-methylamphetamine (PMMA), Methylenedioxymethamphetamine (MDMA), phentermine and DMT exhibited the highest exchange after preloading with diphenhydramine with only 5.5%, 5.2%, 7.8%, 6%, 1.9%, 7.6% remaining in the cells. Less and no exchange were seen with cathine and mescaline, respectively. Dependence on intracellular pH was most pronounced with the methylendioxyamphetamines while uptake of cathine, DOI and cocaine were only moderately affected and mescaline not at all. CONCLUSION: Except for mescaline, all psychostimulants studied here were substrates of the H+/OC antiporter, implicating a strong need for a better characterization of this transport protein.


Assuntos
Antiporters/metabolismo , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Estimulantes do Sistema Nervoso Central/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Antiporters/antagonistas & inibidores , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Células Cultivadas , Estimulantes do Sistema Nervoso Central/farmacologia , Difenidramina/metabolismo , Difenidramina/farmacologia , Relação Dose-Resposta a Droga , Humanos , Imipramina/metabolismo , Imipramina/farmacologia , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Bombas de Próton/metabolismo
4.
Obes Surg ; 31(10): 4371-4375, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34313917

RESUMO

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.


Assuntos
Antieméticos , Laparoscopia , Obesidade Mórbida , Acetaminofen , Difenidramina , Método Duplo-Cego , Gastrectomia/efeitos adversos , Humanos , Obesidade Mórbida/cirurgia , Ondansetron , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Náusea e Vômito Pós-Operatórios/prevenção & controle
5.
J Emerg Med ; 61(3): 259-264, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34148773

RESUMO

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.


Assuntos
Difenidramina , Overdose de Drogas , Adulto , Difenidramina/uso terapêutico , Overdose de Drogas/tratamento farmacológico , Feminino , Humanos , Naproxeno/efeitos adversos , Bicarbonato de Sódio/uso terapêutico , Taquicardia , Adulto Jovem
7.
Future Microbiol ; 16: 409-420, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33847144

RESUMO

Background: Antibiotics are in use since decades to treat various infections caused by Gram-positive and Gram-negative bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. Diphenhydramine, an H1 receptor blocker possesses a weak antibiotic action but when combined with other antibiotics may potentiate their antibacterial activity. Materials & methods: This study investigated in vitro antibacterial activity of diphenhydramine when used alone and in combination with levofloxacin against methicillin-resistant S. aureus and P. aeruginosa. Results: The combined antibacterial effect of the drugs against bacteria showed a fractional inhibitory concentration index of ≤0.5, in other words, synergism. No cytotoxicity was observed as percentage cell viability was >50%. Conclusion: The combination of diphenhydramine and levofloxacin exerted antibacterial activity, and was not found to be cytotoxic when given in combination against P. aeruginosa and S. aureus.


Assuntos
Antibacterianos/farmacologia , Difenidramina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Levofloxacino/farmacologia , Infecções Respiratórias/microbiologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Sinergismo Farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação
8.
Clin Toxicol (Phila) ; 59(10): 918-925, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33666139

RESUMO

BACKGROUND: Diphenhydramine is frequently misused and ingested recreationally for its antihistaminergic and antimuscarinic effects and is often involved in both serious and fatal poisonings, either in isolation or in combination with other xenobiotics. OBJECTIVE: This analysis sought to determine which patient and encounter characteristics were associated with severe outcome after diphenhydramine overdose. METHODS: This is an analysis of the multi-center ToxIC registry (2010-2016). Descriptive analysis of all cases with diphenhydramine listed as the "primary agent" contributing to toxicity were included. Analysis sought to determine which patient and encounter characteristics were associated with severe outcome, defined as occurrence of seizure, ventricular dysrhythmia, or intubation. To determine which patient and encounter characteristics were individually associated with severe outcome, we performed chi-square tests. Fisher's exact tests were used in the case of sparse data. We also performed multivariable logistic regression to further determine independent risk factors for severe outcome in diphenhydramine overdose. RESULTS: Eight hundred and sixty-three cases remained after exclusion with 15.6% (n = 135) of all patients having one or more severe outcome. The most common severe outcome was seizures which occurred in 98 (11.6%) of all ingestions. Females comprised 59.1% (n = 510) of all ingestions. Most ingestions were intentional (86.0%, n = 742) with the most common known reason for an intentional ingestion being self-harm, accounting for 37.5% (n = 324) of all ingestions. Self-harm ingestions and ingestions in males were more commonly associated with intubation. When examining outcomes by age, there were no significant differences overall or in any individual outcome except intubation in which children 0-12 were less likely to be intubated as compared to teens and adults. Signs and symptoms most strongly associated with a severe outcome included acidemia (pH < 7.2), QRS prolongation (QRS > 120 ms), and elevated anion gap (AG > 20). DISCUSSION: Acidemia, QRS prolongation, and elevated anion gap are associated with severe outcomes in diphenhydramine toxicity. Further research is warranted to determine their predictive characteristics.


Assuntos
Difenidramina/envenenamento , Antagonistas dos Receptores Histamínicos H1/envenenamento , Drogas Ilícitas/envenenamento , Antagonistas Muscarínicos/envenenamento , Envenenamento/etiologia , Uso Recreativo de Drogas , Transtornos Relacionados ao Uso de Substâncias/complicações , Tentativa de Suicídio , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Bases de Dados Factuais , Overdose de Drogas , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Oregon , Envenenamento/diagnóstico , Envenenamento/fisiopatologia , Envenenamento/terapia , Prognóstico , Sistema de Registros , Medição de Risco , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto Jovem
9.
Clin Toxicol (Phila) ; 59(11): 1002-1008, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33688782

RESUMO

OBJECTIVES: To describe trends in abuse, misuse, and suicide attempts involving diphenhydramine (DPH). METHODS: We analyzed intentional DPH exposures of individuals ≥10 years old reported to U.S. Poison Control Centers using data from the National Poison Data System, 2005-2016. RESULTS: There were 158,774 intentional DPH exposures in our dataset. The rate of intentional exposures increased 63% over the 12-year study period for all ages combined. Suicide attempts involving DPH showed a bimodal distribution-increasing 263% among children 10-14 years of age, and 126 and 143% among those 55-64 and ≥65 years of age, respectively. Older adults in both the 55-64 and ≥65-year-old age groups had about a 230% increase in rates of misuse. Major adverse clinical effects increased by 91%. There were 745 total reported deaths with a 3.6% increase across all age groups. CONCLUSIONS: Intentional DPH exposures among individuals ≥10 years old have been increasing since 2005. Increasing rates of suicide attempts among children ages 10-14 and increasing misuse among individuals ≥65, coupled with a trend toward greater severity of overdoses, highlight the significant public health impact of this commonly available over-the-counter drug.


Assuntos
Difenidramina/envenenamento , Uso Indevido de Medicamentos/tendências , Overdose de Drogas/epidemiologia , Drogas Ilícitas/envenenamento , Medicamentos sem Prescrição/envenenamento , Tentativa de Suicídio/tendências , Adolescente , Adulto , Idoso , Criança , Overdose de Drogas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
10.
Neurology ; 96(18): e2323-e2331, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33762421

RESUMO

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, p < 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%, p = 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.


Assuntos
Dor Aguda/tratamento farmacológico , Difenidramina/administração & dosagem , Antagonistas dos Receptores de Dopamina D2/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Metoclopramida/administração & dosagem , Cefaleia Pós-Traumática/tratamento farmacológico , Dor Aguda/diagnóstico , Administração Intravenosa , Adulto , Método Duplo-Cego , Quimioterapia Combinada , Serviço Hospitalar de Emergência/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Cefaleia Pós-Traumática/diagnóstico
13.
J Vet Emerg Crit Care (San Antonio) ; 31(3): 380-386, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33749168

RESUMO

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.


Assuntos
Dexametasona/análogos & derivados , Difenidramina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Glucocorticoides/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Hipersensibilidade/veterinária , Animais , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Difenidramina/administração & dosagem , Cães , Quimioterapia Combinada , Glucocorticoides/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Hipersensibilidade/tratamento farmacológico , Masculino , Estudos Retrospectivos
14.
Life Sci Space Res (Amst) ; 28: 18-21, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33612175

RESUMO

The maintenance of pharmacological torpor and hypothermia (body temperature 28 °C - 33 °C) in rats for a week is presented. For this purpose, our laboratory has developed a device (BioFeedback-2) for the feed-back controlled multiple injections of small doses of a pharmacological composition that we created earlier. On the 7th day, the rat spontaneously come out of the pharmacological torpor, the body temperature returned to normal, and on the 8th day, the animal could consume food and water. The proposed approach for maintaining multi-day pharmacological torpor can be applied in medicine, as well as for protecting astronauts during long missions in space.


Assuntos
Hipotermia/induzido quimicamente , Torpor/efeitos dos fármacos , Animais , Temperatura Corporal/efeitos dos fármacos , Difenidramina/administração & dosagem , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos/instrumentação , Retroalimentação , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Ivabradina/administração & dosagem , Sulfato de Magnésio/administração & dosagem , Masculino , Fenotiazinas/administração & dosagem , Propranolol/administração & dosagem , Propiltiouracila/administração & dosagem , Ratos Wistar , Reserpina/administração & dosagem , Serotonina/administração & dosagem , Telemetria/veterinária
15.
J Biol Chem ; 296: 100216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33465377

RESUMO

For most G protein-coupled receptors, the third intracellular loop (IL3) and carboxy-terminal tail (CT) are sites for G protein-coupled receptor kinase (GRK)-mediated phosphorylation, leading to ß-arrestin binding and agonist-specific desensitization. These regions of bitter taste receptors (TAS2Rs) are extremely short compared with the superfamily, and their function in desensitization is unknown. TAS2R14 expressed on human airway smooth muscle cells relax the cell, suggesting a novel target for bronchodilators. To assess IL3 and CT in agonist-promoted TAS2R14 desensitization (tachyphylaxis), we generated fusion proteins of both the WT sequence and Ala substituted for Ser/Thr in the IL3 and CT sequences. In vitro, activated GRK2 phosphorylated WT IL3 and WT CT proteins but not Ala-substituted forms. TAS2R14s with mutations in IL3 (IL-5A), CT (CT-5A), and in both regions (IL/CT-10A) were expressed in human embryonic kidney 293T cells. IL/CT-10A and CT-5A failed to undergo desensitization of the intracellular calcium response compared with WT, indicating that functional desensitization by GRK phosphorylation is at residues in the CT. Desensitization of TAS2R14 was blocked by GRK2 knockdown in human airway smooth muscle cells. Receptor:ß-arrestin binding was absent in IL/CT-10A and CT-5A and reduced in IL-5A, indicating a role for IL3 phosphorylation in the ß-arrestin interaction for this function. Agonist-promoted internalization of IL-5A and CT-5A receptors was impaired, and they failed to colocalize with early endosomes. Thus, agonist-promoted functional desensitization of TAS2R14 occurs by GRK phosphorylation of CT residues and ß-arrestin binding. However, ß-arrestin function in the internalization and trafficking of the receptor also requires GRK phosphorylation of IL3 residues.


Assuntos
Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Miócitos de Músculo Liso/metabolismo , Processamento de Proteína Pós-Traducional , RNA Interferente Pequeno/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Substituição de Aminoácidos , Brônquios/citologia , Brônquios/metabolismo , Cálcio/metabolismo , Difenidramina/farmacologia , Endossomos/metabolismo , Quinase 2 de Receptor Acoplado a Proteína G/antagonistas & inibidores , Quinase 2 de Receptor Acoplado a Proteína G/química , Quinase 2 de Receptor Acoplado a Proteína G/genética , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Mutação , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ligação Proteica , RNA Interferente Pequeno/genética , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Taquifilaxia/genética , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , beta-Arrestinas/genética , beta-Arrestinas/metabolismo
16.
Sr Care Pharm ; 36(2): 83-92, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33509331

RESUMO

OBJECTIVE: The purpose of this systematic review is to evaluate the available evidence for safety and efficacy of over-the-counter (OTC) sleep aids used for the treatment of insomnia in older people.
DATA SOURCES: PubMed, EBSCO, and International Pharmaceutical Abstracts.
STUDY SELECTION: Five studies were included that involved humans 65 years of age and older being evaluated on OTC sleep aids in the outpatient setting.
DATA EXTRACTION: Data extraction from each study included primary and secondary efficacy endpoints, such as differences in the mean total sleep time, sleep latency, sleep efficiency, and number of awakenings, along with safety endpoints, such as psychomotor ability, cognitive ability, and adverse effect profiles. Both subjective and objective measures of changes in sleep and adverse effects were included.
DATA SYNTHESIS: Diphenhydramine had a statistically significant increase in sedation and decrease in number of awakenings but was not shown to be any less or more safe than compared products. Despite lacking safety issues, valerian was found to have no effect on subjective or objective sleep outcomes. Overall, melatonin had the most evidence and was found to have a statistically significant positive impact on sleep measures without safety issues.
CONCLUSION: Diphenhydramine and melatonin appear to be efficacious in improving some sleep measures while causing minimal adverse effects. However, there are very few studies that examine the use of over-the-counter sleep aids in those 65 years of age and older with primary insomnia. Additional studies are needed in this population.


Assuntos
Difenidramina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Melatonina/administração & dosagem , Medicamentos sem Prescrição , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Transtornos do Sono-Vigília/tratamento farmacológico , Sono/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Difenidramina/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Melatonina/efeitos adversos , Valeriana
17.
J Oncol Pharm Pract ; 27(5): 1270-1274, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33148131

RESUMO

INTRODUCTION: As immune checkpoint inhibitors increasingly gain oncological utility, the incidence of unique adverse events may rise as well. The description and management of localized, recurrent muscle spasms secondary to pembrolizumab infusions has not previously been reported. CASE REPORT: A 64-year-old male receiving pembrolizumab infusions experienced acute-onset, isolated spasms and pain occurring in cycles 2 through 5.Management and outcome: Pretreatment with intravenous lorazepam, diphenhydramine, famotidine, ondansetron, and fluids have led to spasm-free pembrolizumab infusions. DISCUSSION: The purpose of this report is to provide the first known incidence and successful corrective measures taken for localized muscle spasms secondary to pembrolizumab infusion.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Espasmo/induzido quimicamente , Difenidramina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Ondansetron/administração & dosagem
18.
J Pharm Sci ; 110(1): 397-403, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32898521

RESUMO

There is increasing evidence that a proton-coupled organic cation (H+/OC) antiporter facilitates uptake of various central nervous system-active drugs, such as the histamine H1 receptor antagonist diphenhydramine, into the brain. The purpose of this study was to clarify the structural requirements for H+/OC antiporter-mediated uptake into hCMEC/D3 cells, an established in vitro model of the human blood-brain barrier, by using a series of diphenhydramine analogs. For this purpose, we synthesized seven tertiary amine analogs and three amide analogs. Uptake of all the amines was facilitated by an outwardly directed H+ gradient and inhibited by pyrilamine, a typical substrate and a strong inhibitor of the H+/OC antiporter. Further, uptake of most of the amines was trans-stimulated by pyrilamine. Uptake of the amines was 21 times faster than that of the amides on average, even though the lipophilicity (log D7.4) of the amines is lower than that of the amides. Amines containing a pyrrolidine or piperidine ring showed the highest uptake rates. Our results suggest that an amine moiety, especially a heterocyclic amine moiety, is important for recognition and transport by the H+/OC antiporter.


Assuntos
Antiporters , Prótons , Antiporters/metabolismo , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Cátions , Difenidramina , Humanos , Proteínas de Transporte de Cátions Orgânicos/metabolismo
19.
Clin Toxicol (Phila) ; 59(4): 351-354, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32914676

RESUMO

INTRODUCTION: Initial research following regulatory changes addressing the pediatric safety of cough and cold medications (CCMs) demonstrated decreases in adverse events (AEs). Using a national multi-source surveillance system, we studied subsequent CCM-related AE case rate trends and associated health-care facility (HCF) evaluation in children. METHODS: Data were collected from 2009 to 2016. Case eligibility included: age <12 years; exposure to an over-the-counter product containing ≥1 CCM pharmaceutical ingredient; ≥1 significant AE that occurred in the United States. RESULTS: About 4756 (72.6%) cases were determined at least potentially related to an index ingredient. Accidental unsupervised ingestions (AUIs; 3134; 65.9%) were the most common case type. Nearly half of AE cases involved children 2 to <4 years old (2,159; 45.4%). The AE case rate did not change significantly over time (p = 0.22). The proportion of AE cases resulting in HCF admission increased from 32.4% (207) in 2009 to 43.4% (238) in 2016 (p < 0.01). Exposures to diphenhydramine (1,305; 67.3%) and/or dextromethorphan (591; 30.5%) were involved in the majority of HCF admissions. CONCLUSIONS: The proportion of AE cases resulting in HCF admission increased from 2009 to 2016. Efforts to prevent AUIs such as packaging innovation and engineering controls, particularly for diphenhydramine and dextromethorphan-containing products, should be pursued.


Assuntos
Antitussígenos/efeitos adversos , Medicamentos Compostos contra Resfriado, Influenza e Alergia/efeitos adversos , Criança , Pré-Escolar , Dextrometorfano/efeitos adversos , Difenidramina/efeitos adversos , Humanos , Medicamentos sem Prescrição/efeitos adversos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Centros de Controle de Intoxicações/estatística & dados numéricos , Estados Unidos/epidemiologia
20.
J Emerg Med ; 60(2): 165-174, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33131965

RESUMO

BACKGROUND: Neuroleptics are commonly prescribed drugs to treat acute conditions (e.g., migraines) in the emergency department, but can cause serious adverse effects. Using diphenhydramine to prevent these adverse effects is very common but remains controversial. OBJECTIVE: We performed a systematic review to determine whether prophylactic administration of diphenhydramine reduces the incidence of neuroleptic adverse effects in patients with acute conditions. METHODS: Medline, Embase, Cochrane, PsycInfo, and Web of Science were searched for randomized controlled trials evaluating any neuroleptic with diphenhydramine vs. the same neuroleptic with any inactive agent. Primary outcome was incidence of any extrapyramidal adverse effect. Secondary outcomes were akathisia, rescue medication, subjective restlessness, neuroleptic malignant syndrome, and sedation. Independent reviewers scanned identified citations, extracted data, and assessed risk of bias. Meta-analysis was performed using random effect models. RESULTS: Of 1566 identified citations, nine studies (n = 1648 patients) met eligibility criteria. Four studies were specifically designed to compare the incidence of neuroleptic adverse effects with and without co-administration of diphenhydramine. Four studies were at high risk of bias. In primary analysis, diphenhydramine had no effect on the incidence of extrapyramidal symptoms (7 studies, n = 1393, risk ratio [RR] 0.75; 95% confidence interval [CI] 0.44-1.31) or akathisia (5 studies, n = 1094; RR 0.78; 95% CI 0.33-1.82) or any of the secondary outcomes. In subgroup analysis, diphenhydramine was associated with a significant decrease in extrapyramidal adverse effects compared with placebo (4 studies, n = 705; RR 0.61; 95% CI 0.41-0.90). Dosage analysis yielded no further information. CONCLUSIONS: When compared with placebo, diphenhydramine was associated with a significant reduction of extrapyramidal adverse effects. Overall quality of evidence is low. Further studies are warranted.


Assuntos
Antipsicóticos , Doenças dos Gânglios da Base , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Antipsicóticos/efeitos adversos , Difenidramina/efeitos adversos , Humanos , Agitação Psicomotora
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