Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the last 20 years, the role of adjuvant pharmacotherapy in optimising outcome in rehabilitation programmes for alcohol-dependent patients has become increasingly evident. New avenues for rational drug treatment have arisen from better understanding of the neurobiological substrates of alcohol dependence, including adaptive changes in amino acid neurotransmitter systems, stimulation of dopamine and opioid peptide systems, and, possibly, changes in serotonergic activity. Disulfiram, naltrexone and acamprosate are currently the only treatments approved for the management of alcohol dependence. However, there is still no unequivocal evidence from randomised controlled clinical trials that disulfiram improves abstinence rates over the long term. Aversive therapy with disulfiram is not without risk for certain patients, and should be closely supervised. Both naltrexone and acamprosate improve outcome in rehabilitation of alcohol-dependent patients, but seem to act on different aspects of drinking pathology. Naltrexone is thought to decrease relapse to heavy drinking by attenuating the rewarding effects of alcohol. However, data from the naltrexone clinical trial programme are somewhat inconsistent, with several large studies being negative. Acamprosate is believed to maintain abstinence by blocking the negative craving that alcohol-dependent patients experience in the absence of alcohol. The clinical development programme has involved a large number of patients and studies, of which the vast majority have shown a beneficial effect of acamprosate on increasing abstinence rates. Both drugs are generally well tolerated; nausea is reported by around 10% of patients treated with naltrexone, while the most frequent adverse effect reported with acamprosate is diarrhoea. Another opioid receptor antagonist, nalmefene, has shown promising activity in pilot studies, and may have a similar profile to naltrexone. Data from studies of SSRIs in alcohol dependence are somewhat heterogeneous, but it appears that these drugs may indirectly improve outcome by treating underlying depression rather than affecting drinking behaviour per se. Similarly, the anxiolytic buspirone may act by ameliorating underlying psychiatric pathology. Dopaminergic neuroleptics, benzodiazepines and antimanic drugs have not yet demonstrated evidence of activity in large controlled clinical trials. Trials with drugs acting at serotonin receptors have yielded disappointing results, with the possible exception of ondansetron. Because the biological basis of alcohol dependence appears to be multifactorial, the future of management of alcoholism may be combination therapy, using drugs acting on different neuronal pathways, such as acamprosate and naltrexone. Pharmacotherapy should be used in association with appropriate psychosocial support and specific treatment provided for any underlying psychiatric comorbidities.
 ...
PMID:Pharmacotherapy of alcohol dependence: a review of the clinical data. 1518 19

Alcohol dependence is a chronic, severe and sometimes fatal disease. Psychological and social support is a crucial element of patient management. Acamprosate and naltrexone are the drugs of choice to help patients remain abstinent, but they are only moderately effective. Nalmefene, an opioid receptor antagonist related to naltrexone, has been authorised in the European Union to help alcohol-dependent patients reduce their alcohol consumption. Nalmefene has not been compared with naltrexone or acamprosate in clinical trials. Clinical evaluation is mainly based on two double-blind, randomised, placebo-controlled trials in which nalmefene was taken "on demand" at a dose of one tablet per day. The trials lasted 6 months and included a total of 1322 patients. During an initial two-week period in which all patients received medical and psychosocial support, about one-third of patients in both trials reduced their alcohol consumption without medication. Depending on the subgroup and the trial, about one-third to one-half of patients discontinued medical treatment before the end of the study period. In both trials, patients taking nalmefene had two fewer "heavy drinking days" per month than patients in the placebo groups. However, at the end of the study, they continued to drink heavily at least one week per month on average. Daily alcohol consumption was 5 to 9 grams lower with nalmefene than with placebo. The most frequent adverse effects observed in clinical trials were insomnia, dizziness, headache and nausea, which were severe in more than 10% of patients. Other serious but less frequent adverse effects included confusion, hallucinations and dissociation, usually at the beginning of treatment. These adverse effects affected about 3% of patients treated with nalmefene, a proportion three times higher than in the placebo groups. The consequences of mixing nalmefene with large amounts of alcohol are not known. In practice, the effects of nalmefene in alcohol-dependent patients seeking to cut down or abstain are of questionable clinical relevance. Adverse effects are frequent and less well-determined than those of standard drugs. The impact of nalmefene on the complications of alcohol dependence is not known. The crucial first step in the management of alcohol-dependent patients is to establish a relationship built on trust and to provide psychological and social support. When medication is considered, it is better to choose acamprosate or naltrexone, drugs that are only moderately effective but better-assessed.
 ...
PMID:Nalmefene. Alcohol dependence: no advance. 2512 Nov 47