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2.
Medicine (Baltimore) ; 99(26): e20785, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590757

RESUMO

BACKGROUND: This study will assess the effect of Xingnaojing injection (XNJI) for the treatment of acute alcoholism (AAH). METHODS: The bibliographic literature sources will be systematically searched in MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure Database, Wan fang Database, and VIP Science Technology Periodical Database. All above electronic databases will be sought from inception to the April 1, 2020. We will not apply any limitations to language and publication time. In addition, we will also search other literature sources. Two reviewers will carry out study selection, data extraction, and methodological quality evaluation, respectively. Any divergences will be resolved by a third reviewer through discussion. We will use RevMan 5.3 software to analyze data analysis. RESULTS: This study will summarize present evidence to assess the effect of XNJI for the treatment of AAH. CONCLUSION: This study will investigate whether XNJI is effective and safety for AAH. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040197.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Injeções , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
4.
BMJ Case Rep ; 12(12)2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31826904

RESUMO

Involuntary movements can be a troublesome condition and represent a real challenge for emergency doctors, particularly for patients of paediatric age. We report a case of a 17-year-old boy with painful involuntary movements mostly affecting his mouth and lower limbs, but also the trunk. After reviewing the patient's history, it was revealed that the adolescent had had acute alcohol intoxication with severe acute agitation and therefore was given a single dose of 10 mg intravenous haloperidol. The concealment of the recent event posed serious difficulties in reaching the diagnosis. When the diagnosis of haloperidol-induced acute dystonia was made, 3 mg of intravenous biperiden was promptly administered with complete clinical resolution in 15 min.


Assuntos
Intoxicação Alcoólica/sangue , Antipsicóticos/uso terapêutico , Distonia/induzido quimicamente , Haloperidol/efeitos adversos , Agitação Psicomotora/etiologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Adolescente , Intoxicação Alcoólica/tratamento farmacológico , Intoxicação Alcoólica/fisiopatologia , Biperideno/uso terapêutico , Distonia/tratamento farmacológico , Distonia/fisiopatologia , Serviço Hospitalar de Emergência , Feminino , Haloperidol/uso terapêutico , Humanos , Parassimpatolíticos/uso terapêutico , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Resultado do Tratamento
5.
Chin J Integr Med ; 25(12): 926-935, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31388972

RESUMO

OBJECTIVES: To investigate the effectiveness and safety of Xingnaojing Injection (XNJ, ) compared with naloxone for the treatment of acute alcohol intoxication (AAI), and provide the latest evidence through evidence-based approach. METHODS: Seven electro-databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure Databases, Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Database (VIP) and Wanfang Database were searched from the inception to January 2018. Randomized controlled trials (RCTs) comparing XNJ with naloxone for patients with AAI and reporting at least one of the below outcomes were included: patients' conscious recovery time, stay length in emergency department, disappearance time of the ataxia symptom, the severity of the symptoms, the blood alcohol content as well as the adverse events. Methodological quality of included trials was assessed using the risk of bias tool which recommended by the Cochrane Collaboration. Meta-analysis was conducted by Review Manager 5.3 software. RESULTS: Totally 141 trials with 13,901 patients were included in this review, all of them were assessed as unclear or high risk of bias. Results showed that on the basis of routine therapy, standard dose XNJ (10-20 mL) may have similar results with naloxone on the recovery time of consciousness (MD 12 min, 95% CI 7.2-17.4 min) and disappearance time of symptoms (MD 6 min, 95% CI-13.8-25.8 min) for patients with AAI. Larger dose of XNJ Injection (21-40 mL) may speed up the time (almost 1 h earlier). Combination of XNJ and naloxone seemed superior to the naloxone alone for all the relevant outcomes. The average difference of time in consciousness recovery was 2 h and the number of AAI patients whose consciousness recovery within 1 h was above 50% the combination group than in the control group (RR 1.42, 95% CI 1.29 to 1.56). No severe adverse events or adverse reactions of XNJ were reported in the included trials. CONCLUSIONS: Low quality of evidence showed XNJ may have equal effect as naloxone and may achieve better effect as add-on intervention with naloxone for patients with AAI. We failed to evaluate the safety of XNJ Injection due to the insufficient evidence in this review. Registration number. in PROSPERO (No. CRD42018087804).


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Naloxona/uso terapêutico , Concentração Alcoólica no Sangue , Estado de Consciência/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Injeções , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Biochemistry (Mosc) ; 84(2): 164-170, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31216975

RESUMO

Quantitative and qualitative assessments of cell membrane components are essential for the accurate interpretation of processes occurring in biological membranes. Changes in the structure and function of cell membrane components have been linked to oxidative stress. Oxidative stress induced by chronic ethanol consumption or cancer transformation has been implicated in changing the levels of phospholipids and fatty acids in the cell membrane. In this study, we used high-performance liquid chromatography to quantitate the effects of alcohol and malignant transformation on membrane components, namely phospholipids and free fatty acids. Ethanol increased the phospholipid levels. Moreover, the process of malignant transformation was accompanied by increased levels of phospholipids and arachidonic acid as well as decreased levels of linoleic acid and α-linolenic acid. Thus, these oxidative stress-inducing conditions that cause variations in the cellular composition affect the actions of the cell membrane and cell function.


Assuntos
Membrana Celular/metabolismo , Fosfolipídeos/metabolismo , Administração Oral , Intoxicação Alcoólica/tratamento farmacológico , Animais , Ácido Araquidônico/química , Ácido Araquidônico/isolamento & purificação , Ácido Araquidônico/metabolismo , Etanol/administração & dosagem , Etanol/toxicidade , Masculino , Estresse Oxidativo , Fosfolipídeos/química , Fosfolipídeos/isolamento & purificação , Ratos , Ratos Wistar
7.
Psychopharmacology (Berl) ; 236(10): 3013-3021, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30919006

RESUMO

RATIONALE: Alcohol has both acute and chronic effects on neuroimmune signaling, including triggering pro-inflammatory cytokine release by microglia. Minocycline, a second-generation tetracycline antibiotic, inhibits microglial activation and reduces neuroinflammation in preclinical studies. In mice, minocycline also reduces ethanol intake, attenuates ethanol-induced conditioned place preference, and inhibits ethanol-induced microglial activation and pro-inflammatory cytokine release. OBJECTIVE: Here, for the first time, we tested the effects of minocycline on subjective response to ethanol and acute ethanol-induced inflammation in humans. METHODS: Forty-eight heavy drinkers participated in a double-blind, placebo-controlled trial in which they were randomized to receive placebo, 100 mg, or 200 mg of minocycline for 10 days. Each subject then underwent two experimental sessions in which they were given a fixed dose of intravenous ethanol using a "clamp" procedure (100 mg%) or placebo (normal saline) on days 8 and 10 of treatment. RESULTS: Minocycline was well tolerated, but there was no effect of either dose of minocycline on subjective response to ethanol or ethanol-induced craving; minocycline effects on cognitive function seem to interact with age. Minocycline treatment did not alter serum cytokine levels at baseline or during ethanol-exposure, although certain baseline cytokine levels predict sedative response to ethanol. CONCLUSION: These findings indicate that a short-term treatment with minocycline may not alter ethanol-related inflammation or subjective response to ethanol in humans. Further research is needed to identify pharmacological agents with robust effects on ethanol-induced inflammation to determine whether neuroimmune modulation represents a viable treatment strategy for alcohol use disorder.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Alcoolismo/tratamento farmacológico , Antibacterianos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Etanol/administração & dosagem , Minociclina/administração & dosagem , Adulto , Intoxicação Alcoólica/imunologia , Intoxicação Alcoólica/metabolismo , Alcoolismo/imunologia , Alcoolismo/metabolismo , Animais , Citocinas/imunologia , Citocinas/metabolismo , Método Duplo-Cego , Humanos , Infusões Intravenosas , Masculino , Camundongos , Microglia/efeitos dos fármacos , Microglia/imunologia , Microglia/metabolismo , Pessoa de Meia-Idade , Adulto Jovem
8.
Pharm Biol ; 57(1): 145-153, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30922154

RESUMO

CONTEXT: Phyllanthus amarus Schumach. and Thonn. (Euphorbiaceae) is traditionally known to improve general liver health. However, its effect on hangover is unknown. OBJECTIVE: This study evaluated PHYLLPRO™, a standardized ethanol extract of P. amarus leaves for protection against oxidative stress and recovery from hangover symptoms. MATERIAL AND METHODS: Ten days daily oral supplementation of 750 mg/day followed by intoxication was evaluated in a randomized placebo-controlled (containing only excipient), crossover study in 15 subjects (21-50 years old), for oxidative stress, liver damage, alleviating hangover symptoms (Hangover Severity Score: HSS) and mood improvement (Profile-of-Mood-Scores: POMS). RESULTS: PHYLLPRO™ was able to remove blood alcohol in the active group while the placebo group still had 0.05% at 12 h post-intoxication (p < 0.0001). For HSS, the active group showed reduced hangover symptoms while there were higher levels of nausea, headache, anorexia, tremulousness, diarrhoea and dizziness in the placebo group (p < 0.05) at hour 10 post-intoxication. Increased fatigue at hour 2 and tension (p > 0.05) from baseline to hour 22 was reported in the placebo group using POMS. Significant anti-inflammatory group effect favouring the active group, by the upregulation of cytokines IL-8 (p = 0.0014) and IL-10 (p = 0.0492) and immunomodulatory effects via IL-12p70 (p = 0.0304) were observed. The incidence of adverse events was similar between groups indicating the safety of PHYLLPRO™. DISCUSSION AND CONCLUSION: Preliminary findings of PHYLLPRO™ in managing hangover, inflammation and liver functions following intoxication, is demonstrated. Future studies on PHYLLPRO™ in protecting against oxidative stress and hangover in larger populations is warranted.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Phyllanthus , Fitoterapia/métodos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Intoxicação Alcoólica/sangue , Biomarcadores/sangue , Estudos Cross-Over , Citocinas/sangue , Suplementos Nutricionais , Método Duplo-Cego , Etanol/sangue , Feminino , Cefaleia/sangue , Cefaleia/tratamento farmacológico , Cefaleia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Extratos Vegetais/farmacologia , Folhas de Planta , Síndrome de Abstinência a Substâncias/etiologia
9.
Neurochem Int ; 124: 238-244, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30682380

RESUMO

Alcohol addiction is a worldwide concern as its detrimental effects go far beyond the addicted individual and can affect the entire family as well as the community. Considerable effort is being expended in understanding the neurobiological basis of such addiction in hope of developing effective prevention and/or intervention strategies. In addition, organ damage and neurotoxicological effects of alcohol are intensely investigated. Pharmacological approaches, so far, have only provided partial success in prevention or treatment of alcohol use disorder (AUD) including the neurotoxicological consequences of heavy drinking. Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous 38 amino-acid neuropeptide with demonstrated protection against neuronal injury, trauma as well as various endogenous and exogenous toxic agents including alcohol. In this mini-review, following a brief presentation of alcohol addiction and its neurotoxicity, the potential of PACAP as a therapeutic intervention in toxicological consequences of this devastating disorder is discussed.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Etanol/toxicidade , Fármacos Neuroprotetores/uso terapêutico , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/uso terapêutico , Intoxicação Alcoólica/metabolismo , Intoxicação Alcoólica/patologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Etanol/administração & dosagem , Humanos , Fármacos Neuroprotetores/farmacologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico
10.
Intern Emerg Med ; 14(1): 143-160, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30187438

RESUMO

The chronic use of alcohol can lead to the onset of an alcohol use disorder (AUD). About 50% of subjects with an AUD may develop alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption and, in 3-5% of them, convulsions and delirium tremens (DTs), representing life-threatening complications, may occur. Unfortunately, few physicians are adequately trained in identifying and treating AWS. The Italian Society on Alcohol has, therefore, implemented a task force of specialists to draw up recommendations for the treatment of AWS with the following main results: (1) while mild AWS may not require treatment, moderate and severe AWS need to be pharmacologically treated; (2) out-patient treatment is appropriate in patients with mild or moderate AWS, while patients with severe AWS need to be treated as in-patients; (3) benzodiazepines, BDZs are the "gold standard" for the treatment of AWS and DTs; (4) alpha-2-agonists, beta-blockers, and neuroleptics may be used in association when BDZs do not completely resolve specific persisting symptoms of AWS; (5) in the case of a refractory form of DTs, the use of anaesthetic drugs (propofol and phenobarbital) in an intensive care unit is appropriate; (6) alternatively to BDZs, sodium oxybate, clomethiazole, and tiapride approved in some European Countries for the treatment of AWS may be employed for the treatment of moderate AWS; (7) anti-convulsants are not sufficient to suppress AWS, and they may be used only in association with BDZs for the treatment of refractory forms of convulsions in the course of AWS.


Assuntos
Intoxicação Alcoólica/diagnóstico , Intoxicação Alcoólica/tratamento farmacológico , Benzodiazepinas/uso terapêutico , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Clormetiazol/uso terapêutico , Humanos , Fenobarbital/uso terapêutico , Propofol/uso terapêutico , Oxibato de Sódio/uso terapêutico , Cloridrato de Tiaprida/uso terapêutico
11.
Sci Adv ; 4(6): eaat2816, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29922720

RESUMO

Mimicking subcellular compartments containing enzymes in organisms is considered a promising approach to substitute for missing or lost cellular functions. Inspired by the multicompartment structures of cellular architectures, we present a novel multienzyme system based on hollow hydrogel microcapsules with flexible enzymatic inverse opal particles. Benefiting from the precise operation capability of the microfluidic electrospray and the remarkable structural color marks in the inverse opal particles, we developed a multienzyme system with controllable number, type, and spatial arrangement of the encapsulated enzymes. The hydrogel shells also could improve enzyme stability against proteolysis in the system. The multienzyme system containing alcohol oxidase and catalase could act as a cascade biocatalyst and reduce alcohol levels in media, providing an alternative antidote and prophylactic for alcohol intoxication. These features indicated that our strategy provides an ideal enzyme cascade reaction system for complex biocatalysis and biomimetic functions of some organelles or organs.


Assuntos
Oxirredutases do Álcool/metabolismo , Materiais Biomiméticos , Catalase/metabolismo , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Dispositivos Lab-On-A-Chip , Células 3T3 , Oxirredutases do Álcool/uso terapêutico , Intoxicação Alcoólica/tratamento farmacológico , Aldeído Desidrogenase/metabolismo , Aldeído Desidrogenase/uso terapêutico , Animais , Biocatálise , Cápsulas , Catalase/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Etanol/metabolismo , Hidrogéis , Camundongos , Microscopia Eletrônica de Varredura
12.
J Ethnopharmacol ; 220: 147-154, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29626671

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Decoctions of Plectranthus species are traditionally ingested after large meals for treatment of food digestion and alcohol abuse. AIM OF THE STUDY: This study aims at associating the digestion-related ethno-uses of Plectranthus species decoctions to molecular mechanism that might explain them: easing digestion (AChE inhibition) and treating hangover (ADH inhibition) MATERIAL AND METHODS: Decoctions from Plectranthus species were analysed for their alcohol dehydrogenase (ADH) inhibition and acetylcholinesterase (AChE) inhibition, related with alcohol metabolism and intestinal motility, respectively. Identification of the active components was carried out by LC-MS/MS and the docking studies were performed with AChE and the bioactive molecules detected. RESULTS: All decoctions inhibited ADH activity. This inhibition was correlated with their rosmarinic acid (RA) content, which showed an IC50 value of 19 µg/mL, similar to the reference inhibitor CuCl2. The presence of RA also leads to most decoctions showing AChE inhibiting capacity. P. zuluensis decoction with an IC50 of 80 µg/mL presented also medioresinol, an even better inhibitor of AChE, as indicated by molecular docking studies. Furthermore, all decoctions tested showed no toxicity towards two human cell lines, and a high capacity to quench free radicals (DPPH), which also play a helpful in the digestive process, related with their RA content. CONCLUSIONS: All activities presented by the RA-rich Plectranthus decoctions support their use in treating digestion disorders and P. barbatus could explain its use also for alleviating hangover symptoms. Medioresinol, which is present in P. zuluensis, exhibited a significant AChE inhibition and may provide, in the future, a new lead for bioactive compounds.


Assuntos
Álcool Desidrogenase/antagonistas & inibidores , Inibidores da Colinesterase/farmacologia , Extratos Vegetais/farmacologia , Plectranthus/química , Acetilcolinesterase/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Intoxicação Alcoólica/tratamento farmacológico , Linhagem Celular , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/isolamento & purificação , Cromatografia Líquida , Cinamatos/química , Cinamatos/isolamento & purificação , Cinamatos/farmacologia , Depsídeos/química , Depsídeos/isolamento & purificação , Depsídeos/farmacologia , Doenças do Sistema Digestório/tratamento farmacológico , Depuradores de Radicais Livres/administração & dosagem , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Humanos , Concentração Inibidora 50 , Medicina Tradicional/métodos , Simulação de Acoplamento Molecular , Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , Espectrometria de Massas em Tandem
13.
Biometals ; 31(2): 217-232, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29392448

RESUMO

Autophagy is a conserved mechanism that plays a housekeeping role by eliminating protein aggregates and damaged organelles. Recent studies have demonstrated that acute ethanol intoxication induces hepatic autophagy in mice. The effect of dietary zinc intake on hepatic autophagic flux during ethanol intoxication has not been evaluated using animal models. Herein, we investigated whether zinc deficiency and excess can affect autophagic flux in the liver in mice and in human hepatoma cells acutely exposed to ethanol. A mouse model of binge ethanol feeding was utilized to analyze the effect of low, adequate, and high zinc intake on hepatic autophagic flux during ethanol intoxication. Autophagic flux was inferred by analyzing LC3II/LC3I ratio, protein levels of p62/SQSTM1, Beclin1 and Atg7, and phosphorylation of 4EBP1. In addition, the degradation of the fusion protein LC3-GFP and the formation of autophagosomes and autolysosomes were evaluated in cells. Ethanol treatment stimulated autophagy in mice and cells. High zinc intake resulted in enhanced autophagy in mice exposed to ethanol. Conversely, zinc deficiency was consistently associated with impaired ethanol-induced autophagy in mice and cells. Zinc-deficient mice exhibited a high degree of ethanol-driven steatosis. Furthermore, zinc depletion increased apoptosis in cells exposed to ethanol. The results of this study suggest that adequate zinc intake is necessary for proper stimulation of autophagy by ethanol. Poor zinc status is commonly found among alcoholics and could likely contribute to faulty autophagy.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Autofagia/efeitos dos fármacos , Suplementos Nutricionais , Zinco/metabolismo , Animais , Apoptose/efeitos dos fármacos , Etanol/toxicidade , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lisossomos/efeitos dos fármacos , Camundongos , Zinco/administração & dosagem , Zinco/deficiência
14.
Rev Recent Clin Trials ; 13(2): 114-125, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29485008

RESUMO

BACKGROUND: Metadoxine is composed of pyroglutamic acid and vitamin B6. Administrations of metadoxine are indicated in cases of acute alcohol intoxication or in chronic alcoholism. OBJECTIVES: To reference all available clinical trials investigating the effects of metadoxine on humans. A focus was put on alcohol intoxication and chronic alcoholism, alcohol abstinence and survival rates. Adverse events were also taken into consideration. Finally, potential roles of metadoxine in treating disorders of the central nervous system will be assessed. METHODS: PRISMA guidelines were followed. Computerised literature searches were performed in July 2017 to retrieve all clinical trials investigating metadoxine from the MEDLINE®, the European Union Clinical Trials Register and the ClinicalTrials.gov databases, using the following equation: "metadoxine". Inclusion criteria were all published clinical trials investigating metadoxine in humans, regardless of outcome measures. Exclusion criteria were articles not abstracted, in vitro studies, studies in rodents, retrospective studies and reviews. RESULTS: Sixteen studies were included. Evidence suggests that metadoxine appears safe to use, as it rarely induced adverse events (reported in 7 out of the 7 studies measuring safety/tolerability). Moreover, metadoxine seems efficient in treating acute alcohol intoxication (2/2 studies) as well as improving liver functions following chronic alcoholism (4/5 studies). Finally, currently on-going clinical trials will reveal if metadoxine could be indicated in attention deficit and hyperactivity disorders as well as fragile X syndrome. CONCLUSION: Metadoxine appears safe to use and seems efficient to improve liver functions following alcohol-related diseases. Further clinical trials will be necessary to determine if metadoxine can be promising for treating brain disorders. PROSPERO registration number: CRD42017072964.


Assuntos
Dissuasores de Álcool/farmacologia , Piridoxina/farmacologia , Ácido Pirrolidonocarboxílico/farmacologia , Intoxicação Alcoólica/tratamento farmacológico , Alcoolismo/tratamento farmacológico , Combinação de Medicamentos , Humanos
16.
Clin Neuropharmacol ; 40(6): 281-285, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29045249

RESUMO

OBJECTIVES: Episodes of agitation are frequent in intoxicated patients who have a substance use disorder, a psychiatric disorder or both (dual diagnosis). For managing the agitation, it is necessary to act promptly in a safe environment and addressing any underlying etiology. Inhaled loxapine improves symptoms of agitation in adults with psychiatric disorders (eg, schizophrenia) within 10 minutes of administration. Recently, some reports have documented the usefulness of loxapine in dual diagnoses patients with agitation. However, the efficacy of loxapine in intoxicated patients has not been deeply addressed. METHODS: This report describes a case series of 12 patients (with addiction or dual disorder) who received inhaled loxapine for symptoms of psychomotor agitation during intoxication with different substances (eg, alcohol, cannabis, or cocaine) at 1 center in Spain. RESULTS: Data from 12 patients were reviewed, 5 patients were attended at the emergency room, 4 at the addiction and dual diagnosis unit, and 3 were treated during hospitalization for detoxification. All patients were under effects of substances. They had substance use disorder (including cannabis, cocaine, alcohol, hypnotics, and hallucinogens), and almost all (90%) presented 1 or more psychiatric disorders. One dose of inhaled loxapine was effective in 9 patients (75%), and in 3 patients, a second dose was required. Only mild dizziness was reported in 1 patient after the second dose. CONCLUSIONS: The acute agitation was effectively and quickly managed with inhaled loxapine in all intoxicated patients and enabled the appropriate clinical evaluation of the agitated state and the patient's management.


Assuntos
Antipsicóticos/administração & dosagem , Serviços Médicos de Emergência/métodos , Loxapina/administração & dosagem , Transtornos Mentais/tratamento farmacológico , Agitação Psicomotora/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Administração por Inalação , Adulto , Intoxicação Alcoólica/complicações , Intoxicação Alcoólica/diagnóstico , Intoxicação Alcoólica/tratamento farmacológico , Feminino , Humanos , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/diagnóstico , Agitação Psicomotora/complicações , Agitação Psicomotora/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/diagnóstico
17.
J Emerg Med ; 53(4): 530-535, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29079068

RESUMO

BACKGROUND: Acute agitation in the setting of alcohol intoxication is commonly encountered in the Emergency Department (ED). In this setting, expert consensus guidelines recommend haloperidol over second-generation antipsychotics due to their limited safety data in alcohol intoxication. OBJECTIVE: The primary objective was to compare vital sign changes prior to and after risperidone administration between ED patients presenting with alcohol intoxication [ETOH (+)] and without alcohol intoxication [ETOH (-)]. The secondary objective was to assess the effect of benzodiazepine co-administration with risperidone on vital signs. METHODS: This was a retrospective chart review of patients who received oral risperidone for acute agitation at two university EDs between January 1, 2012 and December 31, 2015. Vital signs (oxygen saturation, systolic and diastolic blood pressure, heart rate, and respiratory rate) were compared in patients who had ingested alcohol with those who had not. RESULTS: There were 785 patients without evidence of alcohol intoxication who received risperidone in the ED, and 52 patients with alcohol intoxication who received risperidone. Overall, risperidone with and without alcohol intoxication and benzodiazepine administration had no statistically significant effect on vital signs (p = ns for all comparisons). CONCLUSION: This study suggests that oral risperidone may be a safe option for acute agitation in patients presenting to the ED with alcohol intoxication.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Agitação Psicomotora/tratamento farmacológico , Risperidona/farmacologia , Adulto , Antidepressivos de Segunda Geração/farmacologia , Antidepressivos de Segunda Geração/uso terapêutico , Benzodiazepinas/farmacologia , Benzodiazepinas/uso terapêutico , Pressão Sanguínea/fisiologia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Serviço Hospitalar de Emergência/organização & administração , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Taxa Respiratória/fisiologia , Estudos Retrospectivos , Risperidona/uso terapêutico
18.
Int. j. morphol ; 35(3): 942-949, Sept. 2017.
Artigo em Inglês | LILACS | ID: biblio-893078

RESUMO

Prolonged alcohol consumption has consequences on the liver, producing necrotic precipitates and fibrosis, on the pancreas, causing the pancreatic acini to atrophy and destroying insulin-producing cells, and on the central nervous system (CNS), causing the gray and white matter in the frontal lobes of the brain and cerebellum to atrophy. Generally, alcohol is metabolized via oxidative pathways, where the enzymes alcohol dehydrogenase and aldehyde dehydrogenase participate during its metabolization in the liver and CNS, or via non-oxidative pathways during its metabolization in the pancreas. Ethanol metabolism can produce oxidative stress and tissue damage mediated by free radicals, causing morphological and functional alterations in the liver. In the pancreas, it can cause progressive and irreversible damage affecting the endocrine and exocrine functions, a result of the activation of the stellate cells, which are activated directly by alcohol, causing pancreatic fibrosis. In the CNS ethanol can bind directly to proteins, nucleic acids and phospholipids to develop its pathogenesis. The effects produced by alcohol can be counteracted by supplementation with antioxidants, which reduce the inflammation and areas of focal necrosis in the liver, inhibit the activation of pancreatic stellate cells, and reduce oxidative stress in the CNS. Additionally, in order to reduce the negative effects associated with alcohol consumption, recent studies have suggested the administration of antioxidants as a treatment strategy.


El consumo prolongado de alcohol tiene consecuencias en hígado, produciendo precipitados necróticos y fibrosis; en páncreas, provocando atrofia del acino pancreático y destrucción de las células productoras de insulina, y en Sistema Nervioso Central (SNC) generando atrofia de la sustancia gris y blanca en lóbulos frontales del cerebro y cerebelo. En general, el metabolismo del alcohol se consigue mediante las vías oxidativas, donde participan las enzimas alcohol-deshidrogenasa y aldehído deshidrogenasa durante su metabolización en hígado y SNC; o bien, mediante las vías no oxidativas durante su metabolización en páncreas. El metabolismo del etanol es capaz de producir estrés oxidativo y daño tisular mediado por radicales libres, causando alteraciones morfológicas y funcionales del hígado; en el páncreas, puede causar daño progresivo e irreversible afectando las funciones endocrinas y exocrinas de este órgano producto de la activación de las células estrelladas que son activadas directamente por el alcohol generando fibrosis pancreática; mientras que, en SNC se puede unir directamente a proteínas, ácidos nucleicos y fosfolípidos para desarrollar su patogenia. Los efectos producidos por el alcohol pueden contrarrestarse mediante la suplementación con antioxidantes, que reducen la inflamación y las zonas de necrosis focal en el hígado, inhiben la activación de células pancreáticas estrelladas, y reducen el estrés oxidativo en SNC. Asimismo, para reducir los efectos negativos asociados al consumo de alcohol, estudios recientes han propuesto la administración de antioxidantes como estrategia terapéutica.


Assuntos
Humanos , Sistema Nervoso Central/efeitos dos fármacos , Etanol/toxicidade , Intoxicação Alcoólica/tratamento farmacológico , Antioxidantes/uso terapêutico , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Sistema Nervoso Central/patologia , Estresse Oxidativo , Etanol/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia
19.
Drug Alcohol Depend ; 170: 59-65, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27875802

RESUMO

BACKGROUND: Young adults with higher trait urgency (i.e., a tendency to act rashly in response to heightened affect) may be especially vulnerable to heavy drinking. The current study examined 1) the influence of urgency on daily relations between affect and drinking to intoxication, and 2) whether urgency influenced the effectiveness of naltrexone (vs. placebo) for reducing alcohol use. METHODS: This study is a secondary analysis of data from 126 (n=40 female) heavy drinking young adults, ages 18-25, enrolled in a double-blind, 8-week clinical trial comparing brief motivational intervention and either naltrexone or placebo. Multilevel models examined whether trait urgency moderated daily relations between positive and negative affect and drinking to intoxication, measured by an estimated blood-alcohol concentration (eBAC) at or above the legal limit (≥0.08g%). Person-level interactions examined whether naltrexone was more effective than placebo at reducing the odds of eBAC≥0.08g% for individuals with higher vs. lower trait urgency. RESULTS: On days of greater within-person positive or negative affect, young adults with higher urgency were more likely to drink to intoxication than those with lower urgency. Naltrexone reduced the odds of drinking to intoxication significantly more than placebo, independent of positive or negative urgency. CONCLUSIONS: Although naltrexone treatment reduced drinking overall, young adults with higher trait urgency were still at increased risk for hazardous drinking following times of strong positive or negative mood. Targeted interventions are needed to reduce the risk of heavy drinking among young adults with high trait urgency.


Assuntos
Afeto/fisiologia , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Intoxicação Alcoólica/tratamento farmacológico , Motivação/efeitos dos fármacos , Naltrexona/uso terapêutico , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Naltrexona/farmacologia , Adulto Jovem
20.
Life Sci ; 162: 21-4, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27545821

RESUMO

AIMS: The aim of this study was to evaluate possible beneficial effects of treatment with thiamine or benfotiamine in an animal model of acute ethanol intoxication. MAIN METHODS: Thirty male Wistar rats were separated at random into three groups of 10 animals each: Ethanol (E), Ethanol treated with thiamine (T) and Ethanol treated with benfotiamine (BE). Rats were gavaged with single dose of ethanol (5g/kg, 40% v:v). After 30min of ethanol gavage the animals were treated with thiamine or benfotiamine. Six hours after first gavage, the animals were euthanized and blood and liver samples were collected for ethanol and oxidative stress biomarkers quantification. KEY FINDINGS: Serum ethanol levels were higher in animals treated with thiamine or benfotiamine while hepatic alcohol levels were higher in animals of the group treated with benfotiamine comparing to controls or thiamine treated groups. The lipid peroxidation biomarkers were diminished for the groups treated with thiamine or benfotiamine comparing to E animals. Concerning protein oxidative damage parameters, they were enhanced for animals treated with benfotiamine in relation to other groups. SIGNIFICANCE: In conclusion, the treatment with thiamine or benfotiamine even 30min after the massive dose of ethanol has proven to be beneficial against liver damage. Improved results were obtained with benfotiamine in relation to oxidative damage from aqueous compartments.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Modelos Animais de Doenças , Hepatopatias/tratamento farmacológico , Estresse Oxidativo , Tiamina/análogos & derivados , Tiamina/uso terapêutico , Animais , Hepatopatias/metabolismo , Masculino , Ratos , Ratos Wistar
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