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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Difenoximide (SC-26100) is closely related to the antidiarrheal agent, diphenoxylate, which is a chemical congener of meperidine. It has been shown to have a greater ability than methadone to suppress opiate withdrawal in addicted mice, and it has produced less physical dependence than morphine and methadone in laboratory animals. In this study difenoximide was administered to nine active heroin addicts. A dose of 4 mg administered 4 times per day for 3 days effectively suppressed opiate withdrawal, while a dose of 8 mg produced symptoms resembling those of narcotic excess in subjects who had recently self-administered heroin. No side effect were observed at the therapeutic dosage level, and the drug was well accepted by subjects. Difenoximide was shown to be a potentially useful narcotic treatment agent in this impatient study.
Am J Drug Alcohol Abuse 1977
PMID:Use of difenoximide (SC-26100) for narcotic detoxification: a preliminary tolerance and efficacy study. 61 87

Buprenorphine is a mixed opioid agonist/antagonist which appears to produce less physical dependence and respiratory depression than typical mu-agonist opioids. These effects suggest its use for analgesia for drug abusers. However, buprenorphine may precipitate withdrawal from other opioids. The present case illustrates the utility of buprenorphine and describes a method to transfer a patient from a mu-agonist to buprenorphine without precipitating withdrawal or interrupting analgesia.
Am J Drug Alcohol Abuse 1991
PMID:Buprenorphine for pain relief in a patient with drug abuse. 174 7

This chapter examines positive and negative reinforcement mechanisms which play a significant role in alcohol abuse and alcoholism. Consideration is given to the role of euphoria and anxiolytic effects of alcohol as the basis of positive reinforcement, and physical dependence and aversive consequence of drinking as the basis of negative reinforcement. The motivational significance of each of these is discussed with respect to various animal models of addiction and clinical and human research. Brain neurochemistry, neuropharmacology and genetic research data are evaluated from the perspective of reinforcement mechanisms involved with alcohol addiction.
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PMID:Alcohol: mechanisms of addiction and reinforcement. 216 35

A neuroimmunologic model of alcohol withdrawal symptoms is developed according to which these may be considered as an idiopathic auto-immune disease. During the alcohol abuse period of non-addicts, homeostasis may alter pathologically by gradual adaptation of the organism: auto-sensitisation develops and finally leads to the breakdown of auto-immune tolerance of the structural modifications set by alcohol withdrawal. The immunosystem regards the existing assimilation of alcohol as self, the withdrawal of alcohol as non-self. Alcohol withdrawal may be considered as an acknowledged physical stressor, and physical stressors as potential triggers of auto-immune diseases. Some so-called alcohol-induced diseases may originate in the pathogenic effects of preceding auto-immune responses to repeated alcohol withdrawals. Neuroimmunologic preconditions of potential auto-immune diseases exactly fit the alcohol withdrawal situation. Neuroimmunologic diseases themselves show close analogies respectively to alcohol withdrawal symptoms as well as to some alcohol-induced diseases. The myelin basis protein is assumed to be a potential auto-allergen. Finally withdrawal symptoms being the expression of physical dependence on alcohol, the model may highlight the very nature of physical dependence.
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PMID:Alcohol withdrawal syndrome--an auto-immune disease? A neuroimmunologic model for pathogenesis of alcohol withdrawal symptoms. 223 15

This study assessed the impact of family history of alcoholism and antisocial behavior on problem drinking among male first-time DWI offenders. A sample of 123 men in DWI classes were assessed on demographic factors, antisocial behavior and family history of alcoholism. Also, measures of current and past drinking problems were assessed, including scales of perceived ability to control consumption, degree of physical dependence, occurrence of alcohol-related problems and preoccupation with alcohol. The results indicated that while family history of alcohol and antisocial behavior were not significantly related to quantity/frequency of alcohol consumption or alcohol-related problems, family history was related to drink duration. Main effects of family history and antisocial behavior were found for preoccupation with alcohol and physical dependence. There was a significant interaction with respect to perceived ability to control drinking. Results are discussed with regard to the implication that family history of alcoholism and antisocial behavior may influence the development of important precursors to alcoholism.
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PMID:Family history of alcoholism, youthful antisocial behavior and problem drinking among DWI offenders. 272 68

Lipoperoxidation, a degradative process of membranous polyunsaturated fatty acids, has been suggested to represent an important mechanism in the pathogenesis of ethanol toxicity on the liver and possibly also on the brain. Catalysis by transition metals, especially iron, is involved in the biosynthesis of free radicals contributing to lipid peroxidation. Although the exact nature of the redox-active iron implicated in this catalysis is still unknown, it has been well established that lipid peroxidation can be prevented in vitro by iron chelators such as desferrioxamine. Deprivation of redox-active iron through desferrioxamine inhibits by about 50% the microsomal oxidation of ethanol in vitro and reduces very significantly in vivo the overall ethanol elimination rate in rats. Administration of desferrioxamine together with ethanol also reduces the ethanol-induced disturbances in the antioxidant defense mechanisms of the hepatocyte. It also reduces in mice both the severity of physical dependence on ethanol and lethality following the acute administration of a narcotic dose of ethanol. Chronic overloading of rats with iron results, on the opposite, in an increased rate of ethanol elimination, although alcohol dehydrogenase and catalase activities are reduced and cytochrome P-450 depleted in the liver of such iron-overloaded animals. The magnitude of the ethanol-induced increase in lipid peroxidation and decrease in the major membranous antioxidant, alpha-tocopherol, is exacerbated in iron-overloaded rats. Several disturbances of iron metabolism have been reported in human alcoholics. Their contribution to ethanol toxicity appears very likely in the case of hepatic siderosis associated with alcohol abuse. Ethanol could however disturb iron metabolism even in the absence of gross abnormalities of the total iron stores. It is suggested that ethanol intoxication could increase cellular redox-active iron, thus contributing to an enhanced steady-state concentration of reactive-free radicals. This oxidative stress would lead to lipoperoxidative damage and cellular injury.
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PMID:Involvement of iron and iron-catalyzed free radical production in ethanol metabolism and toxicity. 303 5

An empirical biobehavioral research approach to the conditions generally identified as alcohol abuse and alcoholism emphasizes the temporal ordering of participating biochemical, physiological, and behavioral events that provide an operational basis for characterizing the functional aspects of this complex disorder and identifying distinguishable features of the alcohol abuse and dependence process. The available evidence suggests that alcoholism is a condition determined by a host of continuous variables rather than an entity possessing static qualities that imply intractability. The challenge for biobehavioral research is to determine the details of how chronic and excessive alcohol drinking is generated as well as the conditions under which such overindulgence can be attenuated and prevented. Environmental context, for example, can dramatically alter the frequency and amount of alcohol intake. Such contextual malleability is suggested as an important key to at least some of the inconsistencies in the literature with regard to the conditions under which chronic and excessive alcohol intake occurs. Excessive and chronic alcohol ingestion would seem most parsimoniously viewed as a set of behaviors for which others might have been substituted, and intermittently do, rather than as a highly specific disorder or disease. Though current etiological, preventive, and therapeutic orientations emphasize the role of physical dependence and favor genetic influences as strong determinants of alcohol-related disorders, it is important to recognize that troubled drinking is malleable, waxing and then entering periods of remission, with alcohol drinking even in severely dependent individuals remaining susceptible to control by both antecedent and consequating environmental events.
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PMID:A biobehavioral research perspective on alcohol abuse and alcoholism. 314 67

The behaviorally based constructs of DSM-III have differentiated alcohol abuse and dependence, wherein the latter has been characterized by: a history of tolerance and physical dependence; and a history of pathological drinking patterns and/or problems consequent to drinking behavior (APA-DSM III 1980). In contrast, ICD-9 refers to an alcohol dependence syndrome which follows the model proposed by Edwards and Gross in 1976. The WHO memorandum on nomenclature and classification of drug and alcohol related problems has further proposed that alcohol dependence be defined along a continuum of severity, and that dependence be differentiated from severity of alcohol related disabilities (Edwards et al. 1981). In many respects, the alcohol dependence syndrome construct is consistent with Jellinek's disease concept of alcoholism which had its antecedents in medical writings of the late eighteenth and early nineteenth centuries (Lender 1979). Commencing in the early 1960's, many behavioral and social scientists were critical of the disease model of alcoholism. Behavioral researchers found that the drinking behavior of alcoholic subjects could be controlled by its consequences in the laboratory, suggesting that drinking behavior was like any operant. Longitudinal studies of drinking practices suggested that relapse to dependent drinking did not appear to be inevitable. In general, these researchers have utilized behavioral and epidemiological data to prove the null hypothesis: that there was no biological disease behind alcohol addiction. In contrast to the operant studies which served to rebut the disease construct, Ludwig and associates employed a model of Pavlovian conditioning which suggested a relationship between an alcoholic's desire to drink and an increase in autonomic arousal associated with the presence of alcohol (Ludwig et al. 1977).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alcohol dependence: a biobehavioral perspective. 374 8

It is suggested that alcohol, like so many other drugs, is consumed for its rewarding and tension-reducing effects. The progression from use to abuse has many initiating and perpetuating causes at different levels of biological organization, ranging from the molecular to the behavioral level. The interactions between the many causes are better appreciated when they are conceptualized as originating at and progressing from one level to another. Among the perpetuating causes of alcohol abuse may be some of its consequences such as medical diseases and physical dependence. It is hypothesized that at the molecular level an acquired or inherited deficiency of anxiolytic synaptic receptors may be one of several causes of alcohol abuse.
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PMID:Biomedical causes of alcohol abuse. 615 50

The importance of genotypic differences in the determination of sensitivity to ethanol, tolerance development and physical dependence susceptibility is achieving ever greater recognition. It is now generally accepted by investigators studying the biochemical and physiological bases for alcoholism that genotype can influence all these different aspects of sensitivity to the effects of ethanol. Although there is convincing evidence that susceptibility to alcoholism is inherited in man, we have no idea what it is that is inherited [2, 7, 19, 24, 31]. By examining a family history for a particular individual, we can identify individuals at familial risk for developing problems with alcohol abuse. However, environmental as well as genetic factors are important in determining who does and who does not become an alcoholic [4]. Thus, one critical need is for a genetic marker for alcoholism. Since the search for such markers in human research is both expensive and time-consuming, this has led to the use of animal models for alcoholism. Animal models are particularly helpful for genetic research since their genetics are well understood and can be specifically tooled to the task at hand. The goal of this paper is to illustrate the principal genetic methodologies that have been employed to study the human and animal pharmacogenetics of alcohol, and to identify future directions in this area.
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PMID:Pharmacogenetic strategies for studying alcohol dependence. 653 83


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