Evolución de pacientes con adicción al alcohol con el uso de acamprosato / Progression of patients with alcohol dependence using acamprosate

Introducción: los efectos del consumo excesivo de bebidas alcohólicas para el individuo, la familia y la sociedad son un problema de salud, convertido en la más trascendente toxicomanía en la actualidad. En el mercado existen tres fármacos que reducen el deseo de beber y son el disulfiram, la naltrexona y el acamprosato. El acamprosato es el medicamento que se propone estudiar, ya que en Cuba no existen referencias anteriores de estudios de la efectividad del acamprosato. Objetivo: valorar la evolución del alcoholismo y su tratamiento con acamprosato. Métodos: se diseñó un Estudio de Utilización de Medicamentos observacional y descriptivo, basado en las consecuencias prácticas del uso del acamprosato en pacientes diagnosticados con adicción al alcohol, con una dosis de dos cápsulas de 33,3 mg diarias por vía oral, durante seis meses de tratamiento, desde septiembre de 2012 a febrero de 2013. Resultados: de 44 pacientes evaluados, el 90,9 por ciento no tuvo recaídas, solamente el 9,1 por ciento de los pacientes tuvo deseos de consumir alcohol al inicio del tratamiento. Un paciente mostró intranquilidad como efecto adverso al acamprosato. La autovaloración de todos los pacientes fue positiva, refiriendo en su totalidad que cambiaron para una persona mejor. El 68,2 por ciento de los pacientes tuvieron una evolución excelente, lo que coincide con otros estudios internacionales con el acamprosato. Conclusiones: el tratamiento con acamprosato es efectivo para la prevención de las recaídas y la reducción del consumo de alcohol en el alcoholismo(AU)

Introduction: the effects of the excessive intake of alcohol beverages for the individual, the family and the society represent a health problem turned into the most transcendental toxicomania at present times. There are three drugs on the market which reduce the desire of drinking and are called disulfiram, naltrexone and acamprosate. The latter is the drug to be studied since there are no previous references in Cuba about effectiveness study of acamprosate. Objective: to assess the progression of alcoholism and its treatment with acamprosate. Methods: adescriptive and observational Study of Drug Use was designed on the basis of the practical consequences of the use of acamprosate in patients diagnosed with alcohol dependence, at a dose of two caplets of 33.3mg to be taken daily for six months from September 2012 to February 2013. Results: of 44 evaluated patients, 90.9 percent had no relapses, just 9.1 percent felt the desire of taking alcohol beverages at the onset of treatment. One patient showed restlessness as adverse effect of the drug. The self-assessment of all the patients was positive, stating that they changed into a better person after treatment. In the group, 68.2 percent had an excellent progress which agrees with other international study on this drug. Conclusions: the treatment with acamprosate is effective for the prevention of relapses and the reduction of alcohol dependence(AU)

Surreptitious use of disulfiram.

Disulfiram is one of the most important drugs used in the management of alcohol use disorders . It is of significance as a treatment modality especially in low and middle income countries like India, as it is a cheaper pharmacological option compared to other medications like naltrexone and acamprosate.

The Current Situation of Treatment Systems for Alcoholism in Korea

Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.

Choque cardiogênico por dissulfiram / Cardiogenic shock caused by disulfiram / Shockcardiogénico por disulfiram

A intoxicação medicamentosa por dissulfiram é uma situação rara, mas, que pode se apresentar com manifestações cardiovasculares graves e potencialmente fatais, como choque cardiogênico. É apresentado o caso de uma paciente com choque refratário, após intoxicação voluntária por dissulfiram. A avaliação clínica e bioquímica, junto à avaliação ecocardiográfica e à monitorização invasiva, confirmaram tratar-se de um choque cardiogênico associado a esse fármaco. São discutidos os mecanismos de ação conhecidos do dissulfiram e descritos os principais efeitos colaterais, especialmente os cardiovasculares, alertando para a importância da suspeição diagnóstica e da abordagem terapêutica imediata mais adequada nesse contexto.

Drug intoxication with disulfiram is a rare condition that may lead to severe and potentially fatal cardiovascular manifestations such as cardiogenic shock. We report the case of a female patient with refractory shock after deliberate self-poisoning with disulfiram. Clinical, biochemical and echocardiographic assessment, as well as invasive monitoring confirmed cardiogenic shock associated with this drug. The known mechanisms of action of disulfiram are discussed, and the major collateral effects, especially cardiovascular effects, are described. We underscore the importance of suspecting this diagnosis and of adopting prompt and the most adequate therapeutic approach in this context.

La intoxicación medicamentosa por disulfiram es una situación rara, aunque puede presentarse con manifestaciones cardiovasculares graves y potencialmente fatales, como el shock cardiogénico. Este relato presenta el caso de una paciente con shock refractario, tras intoxicación voluntaria por disulfiram. La evaluación clínica y bioquímica, junto a la evaluación ecocardiográfica y el monitoreo invasivo, confirmaron tratarse de un shock cardiogénico asociado a ese fármaco. A lo largo del presente relato se discuten los mecanismos de acción del disulfiram conocidos, así como se describen los principales efectos colaterales, específicamente los cardiovasculares. En este sentido, también se alerta para la importancia de la sospecha diagnóstica y del abordaje terapéutico inmediato más adecuado a este contexto.

Capsule metadoxine in the treatment of alcoholic liver disease: a randomized, double-blind, placebo-controlled, multicenter study / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Capsule metadoxine in the treatment of alcoholic liver disease.</p><p><b>METHODS</b>A randomized double blind multicenter placebo-controlled clinical study was performed to evaluate the therapeutic effectiveness and safety of capsule metadoxine. Patients in metadoxine group received capsule metadoxine 500mg tid po. Patients in placebo group received placebo 2 pillows tid po. The treatment duration was 6 weeks. Patients were followed up 2 weeks after the treatment. Patients were visited once every 3 weeks during the treatment period. Clinical symptoms and liver function were evaluated in all the patients before treatment, at week 3, week 6 and 2 weeks after therapy. CT scan was done in some patients before treatment and at the end point of therapy.</p><p><b>RESULTS</b>254 patients were recruited in the study, 126 in metadoxine group and 128 in placebo group. Median ALT, AST, GGT level in metadoxine group were decreased from 80.0 U/L, 59.2 U/L, 123.0 U/L (before treatment) to 41.1 U/L, 36.0 U/L, 57.0 U/L (after 6 weeks therapy). The improvement in liver function was more significant in metadoxine group than in placebo group (P less than 0.05). For the patients who stopped drinking during the study, the total effective rate of improvement in liver function was 82.8% in metadoxine group, much higher than that in placebo group (55.7% , P=0.0000). For the patients who did not stop drinking during the study, the total effective rate of improvement in liver function was 65.4% in metadoxine group, which is not significantly higher than that in placebo group (44.8%, P=0.1767). The CT value ratio of liver to spleen was significantly improved in metadoxine group (P=0.0023), and there was no significant difference between the two groups (P=0.6293). The rate of adverse was 1.6% in both of groups.</p><p><b>CONCLUSION</b>Capsule metadoxine is an effective and safe treatment for alcoholic liver disease.</p>

Actualización del tratamiento farmacológico de la dependencia alcohólica / Pharmacological review of alcoholic dependence treatment

El objetivo de la presente actualización farmacológica es abordar la problemática de la dependencia alcohólica. Partiendo de las bases biológicas y del impacto del etanol sobre los sistemas neurobiológicos y de neurotransmisión, se hará una revisión de las principales herramientas farmacológicas para el tratamiento de la dependencia alcohólica. El disulfiram, la naltrexona y el acamprosato, todas ellas con aprobación por la FDA (Food and Drug Administration) han mostrado mecanismos de acción, perfiles de eficacia, tolerabilidad y adherencia dispares. También nos referiremos al topiramato, el que está siendo estudiado actualmente con relación a esta indicación.

The aim of the present pharmacological update is to revise the problem of alcohol dependence. Starting from the biological bases and the impact of alcohol on the neurobiological and neurotransmission systems, a revision of the main pharmacological tools for alcohol dependence treatment will be done. Disulfiram, naltrexone, acamprosate, all of them approved by the FDA (Food and Drug Administration), have shown mechanisms of action, efficacy, tolerance and adherence dissimilar. We will also refer to topiramate, which is being studied for this indication.

Tratamiento del tinnitus en hipoacusias neurosensoriales de curvas descendentes por modulación de los neurotransmisores con el uso de acamprosato: experiencia clínica / Tinnitus treatment by neurotransmitter modulation in high frequency sensorineural hearing loss using Acamprosate: a clinical experience

Introducción: El tinnitus neurosensorial está correlacionado con numerosas patologías del oído interno y de su vía central y que pueden originarse en cualquier nivel de ésta; sin embargo todas estas noxas pueden manifestarse igual en corteza auditiva, como una sensación auditiva sin mediar un estímulo acústico externo, de tal manera que este mensajero común deben ser los neurotransmisores. Se han descrito dos en la vía auditiva aferente: el glutamato que es excitatorio y el GABA que es inhibitorio. Numerosos estudios revelan que el tinnitus neurosensorial se produciría por un desbalance de estos dos neurotransmisores con predominio excitatorio. El acamprosato es un fármaco usado en el alcoholismo que actuaría modulando el equilibrio GABA-glutamato. Existe un sólo estudio publicado con el uso del acamprosato en el tinnitus con una mejoría o disminución de su intensidad en 80 por ciento o más de los casos. Objetivos: Conocer la real utilidad del fármaco pues en este estudio, arriba mencionado, la evaluación fue sólo subjetiva y sin seguimiento. Material y Método: Fueron estudiados 20 pacientes tratados por un mes efectuándose tinnitumetría, evaluación psicoemocional (THI) y seguimiento. Resultados: De los 20 pacientes, en dos desapareció el tinnitus, en seis bajaron los niveles de la tinnitumetría en 5 dBo más con mejoría del THI en 50 por ciento o más y en doce pacientes la mejoría fue menor o ninguna. Conclusiones: Sería posible modular los neurotransmisores de la vía auditiva aferente con éxito, en aquellos pacientes con tinnitus severo. Es un estudio original con un respaldo fisiopatológico que abre nuevas perspectivas terapéuticas.

Pharmacotherapy for Alcohol Dependence: Anticraving Medications for Relapse Prevention

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence.These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence.

Uso do acamprosato no tratamento do zumbido: um estudo duplo-cego / Tinnitus treatment with acamprosate: double-blind study

O tratamento do zumbido é, ainda nos dias de hoje, um grande desafio para os otorrinolaringologistas. Várias lacunas persistem em sua fisiopatologia, tendo como resultado vários tipos de tratamento, com resultados muito irregulares. O acamprosato é uma droga utilizada no tratamento do alcoolismo, devido à sua ação reguladora da transmissão glutamatérgica e GABA-érgica, nunca tendo sido empregado no tratamento do zumbido. OBJETIVO: Avaliar a segurança e eficácia do uso do acamprosato, no tratamento do zumbido de causa neurossensorial. FORMA DE ESTUDO: ensaio clinico randomizado. MATERIAL E MÉTODO: 50 pacientes com zumbido de causa neurossensorial foram divididos em 2 grupos, 25 recebendo acamprosato e 25 placebo por 3 meses, em um estudo prospectivo duplo-cego, sendo analisados os efeitos terapêuticos e efeitos colaterais, de acordo com escala (nota) de 1 a 10, atribuída pelo próprio paciente. RESULTADOS: Foi observado algum grau de melhora sintomatológica em 86,9 por cento dos pacientes, sendo que em 47,8 por cento dos casos observamos melhora superior a 50 por cento, dados estatisticamente significativos em relação ao placebo. A incidência de efeitos colaterais encontrada foi baixa (12 por cento) e de intensidade leve, com boa tolerabilidade geral. CONCLUSÃO: O acamprosato, medicação utilizada no tratamento do alcoolismo, é eficaz e seguro para o tratamento do zumbido de causa neurossensorial, com percentual de melhora superior à maioria das medicações utilizadas para o tratamento do zumbido, constituindo uma excelente alternativa terapêutica.

Feeding deterrent and growth inhibitory properties of larval frass against spodoptera littoralis [boisd.]

The research has been conducted to evaluate the activity of the frass extracts of Spodoptera littoralis [Boisd.] against its larvae. Five solvents differ in their polarity namely petroleum ether; chloroform; acetone; ethanol and water were used to extract the frass material The following points were studied: [a] evaluation the toxicity of different extracts against S. littoralis larvae [b] effect of frass extracts on the development of S. littoralis larvae [c] evaluation of the antifeedant activity of frass extracts against 4th instar larvae of S littoralis. Results showed that the 10% concentration of frass exhibited strong antifeedant activity. On the other hand ethanol and water extracts [highly polar] caused the highest mortality percentage whilst petroleum ether and chloroform [non-polar] caused the highest percentage of antifeedant activity, respectively. The type and concentration of extracts by water, ethanol, chloroform and acetone affected the sex ratio and development of S. littoralis. In general, the biological activity of frass extracts was solvent type-and concentration-dependent

Tratamento farmacológico da dependência do álcool / The pharmacologic treatment of the alcohol dependence

As intervencões farmacológicas podem ter um papel crucial na reducão do craving, consumo de álcool e manutencão da abstinência. Este artigo revisa a farmacoterapia para a dependência de álcool com ênfase na naltrexona, dissulfiram e acamprosato. O antagonista opióide naltrexona diminui taxas de recaída, reduz dias de consumo e prolonga períodos de abstinência. Acamprosato restaura a atividade normal dos sistemas glutamato e GABA. Dissulfiram tem demonstrado ser mais efetivo para pacientes que acreditam em sua eficácia e permanecam aderentes ao tratamento. Ondansetron tem-se mostrado promissor na dependência de álcool de início precoce, mas necessita estudos mais extensivos. Topiramato (até 300 mg/dia) foi mais eficaz do que placebo no tratamento da dependência de álcool.

Efficacy of acamprosate in the treatment of alcohol-dependent outpatients

OBJECTIVE: To evaluate the efficacy and security of acamprosate in the treatment of 75 men, aged 18 to 59 years, with diagnosis of alcohol dependence according to the ICD-10. METHODS: Double-blind, placebo-controlled study, 24-week long. After a one-week detoxification period, patients were randomly divided in two groups: the first group received acamprosate (six tablets of 333 mg/d for 12 weeks) and the second group received placebo (six tablets for 12 weeks). After the first 12 weeks, patients continued the follow-up for further 12 weeks without medication. RESULTS: Patients who were receiving acamprosate showed significantly higher continuous abstinence time within the 24 weeks of treatment compared with patients who were assigned to placebo treatment (p=.017). Twenty-five percent of patients who were receiving acamprosate and 20 percent of the placebo-treated patients dropped out. Few side-effects were reported in both groups. CONCLUSION: Acamprosate proved to be safe and effective in treating alcohol-dependent patients and to maintain the abstinence during 24 weeks

Psychosis during disulfiram therapy for alcoholism.

Fifty-two patients (51 males, one female) of alcohol dependence/abuse diagnosed according to DSM 111 R1 were registered for disulfiram treatment and were admitted for a 4-week period. No alcohol challenge test was given during their hospital stay. Disulfiram tablets were administered 250 mg twice daily after food. After one week's hospital stay with disulfiram therapy they were sent home to be followed up initially after 15 days and later on once a month. Six male patients developed psychotic symptoms. All of them had shown a mood disorder but no thought disorder was observed. Psychotic symptoms remitted completely after withdrawing disulfiram and then a short course of antipsychotic therapy was given, except in one patient who had to be given lithium for remission of symptoms.

In vitro effect of dithiocarbamate pesticides and of CaNa2EDTA on human serum dopamine-beta-hydroxylase / 生物医学与环境科学（英文）

Serum dopamine-beta-hydroxylase (DBH) inhibition has been reported in lead workers treated with CaNa2EDTA and in alcoholic patients repeatedly treated with the alcohol aversive drug Disulfiram. The mechanism of inhibition involves Cu++ chelation at the active site of DBH. The effect of CaNa2EDTA and Disulfiram on serum DBH has been compared to the effect of dithiocarbamate pesticides in vitro for the possible use of serum DBH determination for the biological monitoring of workers exposed to these pesticides. Most dithiocarbamates inhibit human serum DBH at micromolar concentrations (range of I50, 0.027-1.6 mumol/L). The inhibitory potency increased from methyl- and dimethyl dithiocarbamates to diethyl dithiocarbamates up to the most potent ethylene bisdithiocarbamates. The I50 of CaNa2EDTA was 3.8 mumol/L, higher than those of dithiocarbamates. Copper addition to the test system reactivated at stoichiometric concentrations dithiocarbamate-inhibited DBH indicating that both base line values and percent of inhibition can be calculated in a single blood sample. Results suggest that serum DBH determination could be useful in case of acute poisoning involving high doses of dithiocarbamate pesticides.

El Piracetam en el Sindrome de abstinencia alcohólica / Piracetam in the Alcoholic withdrawal syndrome

Se efectuó un estudio abierto para apreciar la eficacia del piracetam en el síndorme agudo de la abstinencia alcohólica. Se estudiaron 30 pacientes varones con una edad promedio de 40 años y una crisis reciente de ingestión alcohólica de 17 días en promedio. La mayor parte eran consumidores de bebidas destiladas. 20 de estos pacientes tenían hospitalizaciones previas por alcoholismo; el registro de su respuesta a tratamientos anteriores pudo entonces servir de comparación para evaluar los resultados del tratamiento actual. 18 pacientes tuvieron alucinaciones y 2 desarrollaron un cuadro moderado de delirium tremens. La ansiedad y la agitación, así como los síntomas depresivos, fueron comunes. Durante 5 días, se administraron 9 gramos diarios de piracetam por vía endovenosa, fraccionados en tres dosis, y se evaluaron los signos y síntomas de los sujetos diariamente según una escala de 23 ítems clínicos. Dos pacientes abandonaron el ensayo antes de su fin. La apreciación general de los resultados fué favorable, destacándose la ausencia de somnolencia o letargia y l mayor vitalidad general en comparación con otros tratamientos. Para el quinto día, sólo 12 pacientes presentaban signos y síntomas ligeros de depresión y/o ansiedad. El piracetam parece superar a los fenotiazínicos y tener algunas ventajas sobre los benzadiazepínicos en el tratamiento de estos pacientes