Alcoholism physical dependence

Chronic administration of opiates and alcohol leads to physical dependence a phenomenon, which is only weakly expressed following chronic administration of psychostimulants or other drugs of abuse. Physical dependence results from neuroadaptive intracellular changes to an altered pharmacological state. Abstinence from chronic opiate or alcohol use leads to a variety of physiological and psychological withdrawal symptoms based on these adaptations of the neuronal system. 

Ator NA, Weerts EM, Kaminski BJ, et al Zaleplon and triazolam physical dependence assessed across increasing doses under a once-daily dosing regimen in baboons. Drug Alcohol Depend 61 69-84, 2000... 

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

Figure 23.2 A schematic diagram illustrating the ways in which the CNS counters the depressant effects of a drug such as alcohol or an opioid and how this leads to the manifestation of physical dependence when there is abstinence from the drug. These excitatory compensations produce symptoms opposite to the acute effects of the drug...

Trujillo K., Akil H. Excitatory amino acids and drugs of abuse a role for A-methyl-D-aspartate receptors in drug tolerance, sensitization and physical dependence. Drug Alcohol Depend. 38 139, 1995. 

The side effects of barbiturates include sedation, poor physical coordination, and impaired mental performance. They also potentiate the intoxicating effects of alcohol. Barbiturates can be extremely dangerous in overdose, causing anesthesia, coma, and even death. In addition, barbiturates can cause dangerous suppression of breathing in patients with sleep apnea or other respiratory disorders. With repeated use over just a few weeks, physical dependence and tolerance to their effects can develop, leading to increasing doses to maintain the desired therapeutic effect. If a... 

Side effects of benzodiazepines include sedation, dizziness, poor coordination, and, at higher doses, amnesia. Benzodiazepines also increase the effects of alcohol therefore, alcohol use should be avoided or markedly curtailed. Benzodiazepines can also exacerbate the breathing problems of patients with sleep apnea and other respiratory disorders such as emphysema. Like the barbiturates, long-term use of benzodiazepines can lead to physical dependence, and abrupt discontinuation can produce an unpleasant, or even dangerous, withdrawal syndrome. 

In contrast, some drugs of abnse prodnce intense craving and are highly addictive bnt do not prodnce physical dependence. The absence of physical dependence indicates the relative lack of physiological withdrawal. This is not synonymous with meaning that discontinuation of these componnds may not be psychologically nncomfortable. Two examples are marijnana and cocaine. One need only look to the recent crack epidemic to see evidence of the way these substances can destroy lives, bnt they do not produce tolerance or risk of withdrawal to the same extent as alcohol or heroin. As a result, we would say that the daily crack or marijuana user meets the dehnition of substance dependence bnt does not exhibit true physical (or physiological) dependence. 

Chronic excessive consumption of alcohol can result in physical dependence or alcoholism. There is often a steady progress in the need to drink, so that the person starts drinking early in the day to maintain blood alcohol levels and avoid withdrawal effects. Alcoholism often results in a variety of organ system effects, some of which are related to accompanying malnutrition. Treatment for alcoholism must address the withdrawal effects as well as associated vitamin deficiencies associated with malnutrition. 

Most of the research and results have been focused on the effects of drug therapy on the disorders induced by alcohol, and by opiates abuse. For all drugs, the first objective is to wean the patients from the drug, treating or preventing the effects of withdrawal for those drugs which cause physical dependence (alcohol, nicotine, opiates, caffeine, certain psychotropic agents such as benzodiazepines, possibly antidepressants). The second phase is the prevention of recurrence or relapse, which relies on a com-... 

Withdrawal from long-term high-dose use of alcohol or sedative-hypnotic drugs can be life threatening if physical dependence is present. Benzodiazepines, such as chlordiazepoxide Librium) and diazepam Valium), are sometimes used to lessen the intensity of the withdrawal symptoms when alcohol or sedative-hypnotic drug use is discontinued. Benzodiazepines are also employed to help relieve the anxiety and other behavioral symptoms that may occur during rehabilitation. 

All of the CNS depressants can pass through the placenta. Newborn babies with dependent mothers may be physically dependent themselves and have withdrawal symptoms that include tremors, irritability, hyperactivity, and feeding and breathing problems. There may be birth defects such as fetal alcohol syndrome, which consists of abnormal facial features, a small head, mental retardation, and poor coordination. 

It is a pure antagonist and chemically related to naloxone. It is more potent than naloxone and because of its longer duration of action, it can be used as maintenance drug for morphine addicts. It has no euphoric effect and no physical dependence liability. It is effective orally. It is also claimed to be beneficial in decreasing craving for alcohol in alcoholics. Side effects include gastrointestinal disturbances and muscular pain. 

It is associated with development of psychic dependence, tolerance and physical dependence and sudden withdrawal of alcohol may lead to withdrawal syndrome. 

Chronic alcohol drinkers, when forced to reduce or discontinue alcohol, experience a withdrawal syndrome, which indicates the existence of physical dependence. Alcohol withdrawal symptoms classically consist of hyperexcitability in mild cases and seizures, toxic psychosis, and delirium tremens in severe ones. The dose, rate, and duration of alcohol consumption determine the intensity of the withdrawal syndrome. When consumption has been very high, merely reducing the rate of consumption may lead to signs of withdrawal. 

Naltrexone is generally taken once a day in an oral dose of 50 mg for treatment of alcoholism. An extended-release formulation administered as an IM injection once every 4 weeks is also effective. The drug can cause dose-dependent hepatotoxicity and should be used with caution in patients with evidence of mild abnormalities in serum aminotransferase activity. The combination of naltrexone plus disulfiram should be avoided, since both drugs are potential hepatotoxins. Administration of naltrexone to patients who are physically dependent on opioids precipitates an acute withdrawal syndrome, so patients must be opioid-free before initiating naltrexone therapy. Naltrexone also blocks the therapeutic effects of usual doses of opioids. 

Naltrexone Nonselective competitive antagonist of opioid receptors Reduced risk of relapse in individuals with alcoholism Available as an oral or long-action parenteral formulation Toxicity Gastrointestinal effects and liver toxicity will precipitate a withdrawal reaction in individuals physically dependent on opioids and will prevent the analgesic effect of opioids... 

Senay, E.C. et al., Physical dependence on Ultram (tramadol hydrochloride) both opioid-like and atypical withdrawal symptoms occur, Drug Alcohol Depend., 69, 233, 2003. 

Greenwald, M. and Stitzer, M., Butorphanol agonist effects and acute physical dependence in opioid abusers comparison with morphine, Drug Alcohol Depend., 53, 17, 1998. 

Drug(s) Alcohol Classification/ Action Sedative-hypnotic Route/Method of Administration Oral, from various beverages [wine, beer, other alcoholic drinks] Effect Desired by User Euphoria relaxed inhibitions decreased anxiety sense of escape Principal Adverse Effects Physical dependence impaired motor skills chronic degenerative changes in the brain, liver, and other organs Additional Information See Chapter 6... 

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