Chick J. Safety issues concerning the use of disulfiram in treating alcohol dependence. (review). Drug Safety 20(5): 427-435, 1999. (50 refs.)
Disulfiram is known to cause hepatitis, which is sometimes fatal. The best estimate of the frequency of disulfiram-induced fatal hepatitis is 1 case in 30,000 patients treated/year. Its appears to be more common in patients given disulfiram for the treatment of nickel sensitivity. Frequent blood testing for liver function is probably not necessary, but patients taking disulfiram should be in regular contact with a physician. There are rare reports of psychosis and confusional states in conjunction with disulfiram treatment and peripheral neuropathy and optic neuritis have been reported; these effects are dose-related. Psychiatric complications appear to be more common with the use of disulfiram in India than in Western countries. Of the less serious adverse effects, tiredness, headache and sleepiness are the most common. Deaths from the disulfiram-alcohol (ethanol) interaction have not been reported in recent years, possibly because the dosages used are lower than those used 40 years ago, and patients with cardiac disease are now excluded from treatment. There is no evidence to suggest that disulfiram causes cancer. Of note, there are drug interactions with compounds that utilise the cytochrome P450 enzyme system. Disulfiram can be viewed as a drug with a moderate record of adverse effects. Alcohol dependence, for which it can be a helpful treatment, is associated with a high morbidity and mortality. Copyright 1999, Adis International, Ltd.
Chikritzhs TN; Jonas HA; Stockwell TR; Heale PF; Dietze PM. Mortality and life-years lost due to alcohol: A comparison of acute and chronic causes. Medical Journal of Australia 174(6): 281-284, 2001. (15 refs.)
Objectives: (i) To estimate the numbers of deaths and person-years of life lost (PYLL) due to high-risk alcohol consumption in Australia during 1997, using current estimates of consumption. (ii) To compare the number of deaths and PYLL due to acute conditions associated with bouts of intoxication and chronic conditions associated with long- term misuse of alcohol. Methods: All Australian deaths during 1997 related to conditions considered to be partially or wholly caused by high-risk alcohol consumption were extracted from the Australian Bureau of Statistics Mortality Datafile and adjusted by alcohol aetiologic fractions calculated for Australia in 1997. A life-table method was used to estimate the PYLL for deaths from alcohol-caused conditions. Main outcome measures: Numbers of all deaths and PYLL due to chronic and acute alcohol-related conditions. Results: Of the 3290 estimated alcohol-caused deaths in 1997, chronic conditions (eg, alcoholic liver cirrhosis and alcohol dependence) accounted for 42%, acute conditions (eg, alcohol-related road injuries and assaults) for 28% and mixed (chronic and acute) for 30%. Of the 62914 estimated potential life years lost, acute conditions were responsible for 46%, chronic for 33% and mixed for 21%. The average number of years of life lost through deaths from acute conditions was more than twice that from chronic conditions, because the former mostly involved younger people. Conclusions: in view of the societal burdens imposed by premature deaths, more effective public health strategies are needed to reduce the harm associated with occasional high-risk drinking las well as sustained high-risk drinking), especially among young people. Copyright 2001, Australasian Medical Publishing Co., Ltd.
Chiriboga CA. Fetal alcohol and drug effects. (review) Neurologist 9(6): 267-279, 2003. 130 refs.)
Background: Alcohol and drug use by pregnant women are harmful to the developing embryo and fetus. Teasing apart the specific contributions of each substance to adverse child outcome, however, proves difficult in practice. The risks to the neonate include intrauterine growth retardation, birth defects, altered neurobehavior, and withdrawal syndromes. Subsequent behavior, development, and neurologic function may also be impaired. Review Summary: Maternal cigarette smoking carries the greatest risk of impaired fetal growth of any of the substances discussed herein and has been linked to subsequent externalizing behaviors. Alcohol is a well-established teratogen. Heavy exposure to alcohol in a subset of infants is associated with fetal alcohol syndrome (FAS). Mental retardation is one of the main sequelae of alcohol exposure in utero. Fetal marijuana exposure has no consistent effect on outcome. Prenatal cocaine exposure has not been shown to have any detrimental effect on cognition, except as mediated through cocaine effects on head size. Although fetal cocaine exposure has been linked to numerous abnormalities in arousal, attention, and neurologic and neurophysiological function, most such effects appear to be self-limited and restricted to early infancy and childhood. Opiate exposure elicits a well-described withdrawal syndrome affecting central nervous, autonomic, and gastrointestinal systems, which is most severe among methadone-exposed infants. Conclusion: Most adverse effects of prenatal drug exposure are self-limited, with catch-up growth and resolution of withdrawal and of prior neurobehavioral abnormalities noted over time. The exception is alcohol, which is linked to life-long impairments (i.e., mental retardation and microcephaly) and possibly cigarette-related behavioral effects. The absence of tangible evidence of detrimental long-term cocaine effects may reflect limitations in the methodology used to identify children at greatest risk for adverse outcome. Copyright 2003, Lippincott, Williams & Wilkins
Cohen AD; Halevy S. Alcohol intake, immune response, and the skin. Clinics in Dermatology 17(4): 411-412, 1999. (28 refs.)
Increased alcohol consumption has been associated with dermatological diseases including psoriasis, rosacea, nummular eczema, acne, porphyria cutanea tarda, and facial flushing. As alcohol consumption is associated with liver cirrhosis and malnutrition, the skin manifestations of these diseases may also indicate alcohol misuse. Alcohol seems to affect dermatological diseases by influencing metabolism (e.g., porphyria cutanea tarda), cutaneous vasculature (e.g., rosacea), and the immune response. Patients who consume alcohol excessively are at increased risk for infectious diseases, including HIV infection. When alcoholics develop an infectious disease, it is associated with increased morbidity and mortality. Immune suppression secondary to both malnutrition and liver disease may occur following alcohol consumption, however, as the frequency and severity of infections are so pronounced among alcoholics, is seems that alcohol by itself may suppress the immune system. It is apparent that alcohol is associated with dermatological diseases, some of which have an immune pathogenetic mechanism (e.g., psoriasis); however, as laboratory evidence for he influence of alcohol on such dermatoses is scarce, further in vitro studies are necessary to clarify the influence of alcohol and its metabolites on the skin. Copyright 1999, Elsevier Science, Inc.
Crews FT; Nixon K. Alcohol, neural stem cells, and adult neurogenesis. Alcohol Research & Health 27(2): 197-204, 2003, (25 refs)
Recent research demonstrates that neural stem cells divide throughout life and give rise to new neurons, a process known as neurogenesis. This article addresses two principal questions concerning alcohol and adult neurogenesis: To what extent are neurogenesis in the adult brain and the risk for alcoholism governed by similar factors? And, to what extent and through what mechanisms do alcohol use and alcoholism affect adult neurogenesis? This article also discusses genetic and environmental influences on risk for alcoholism and on regulation of neurogenesis; the possibility that modulation of neurogenesis contributes to alcoholic pathology; and the evidence that alcohol disrupts neurogenesis in the adult brain, and the neurochemical processes by which this may occur. In animal models, high doses of alcohol have been shown to disrupt neurogenesis, and may underlie long–term deficits in hippocampal structure and function. More moderate but chronic alcohol consumption also affects neurogenesis, suggesting that inhibition of neurogenesis may contribute to the neurodegeneration associated with chronic alcoholism. Alcohol may lead to disruptions in neurogenesis in several ways: through increased levels of glucocorticoids triggered by stress, direct inhibition of glutamate–NMDA receptors, serotonin dysregulation, and inhibition of growth factor–mediated cell proliferation. Research is needed to more directly determine the function of adult neurogenesis and how alcohol–induced inhibition of neurogenesis might contribute both to the pathology and the behavioral changes associated with alcohol abuse. Public Domain
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