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As with similar substances with a sedative-hypnotic mechanism, such as barbiturates and benzodiazepines, withdrawal from alcohol dependence can be fatal if it is not properly managed.[46][52] Alcohol's primary effect is the increase in stimulation of the GABAA receptor, promoting central nervous system depression. With repeated heavy consumption of alcohol, these receptors are desensitized and reduced in number, resulting in tolerance and physical dependence. When alcohol consumption is stopped too abruptly, the person's nervous system suffers from uncontrolled synapse firing. This can result in symptoms that include anxiety, life threatening seizures, delirium tremens, hallucinations, shakes and possible heart failure.[53][54] Other neurotransmitter systems are also involved, especially dopamine, NMDA and glutamate.[10][55] Severe acute withdrawal symptoms such as delirium tremens and seizures rarely occur after 1 week post cessation of alcohol. The acute withdrawal phase can be defined as lasting between one and three weeks. In the period of 3 – 6 weeks following cessation increased anxiety, depression as well as sleep disturbance is common;[56] fatigue and tension can persist for up to 5 weeks as part of the post-acute withdrawal syndrome; about a quarter of alcoholics experience anxiety and depression for up to 2 years. These post-acute withdrawal symptoms have also been demonstrated in animal models of alcohol dependence and withdrawal.[57] A kindling effect also occurs in alcoholics whereby each subsequent withdrawal syndrome is more severe than the previous withdrawal episode; this is due to neuroadaptations which occur as a result of periods of abstinence followed by re-exposure to alcohol. Individuals who have had multiple withdrawal episodes are more likely to develop seizures and experience more severe anxiety during withdrawal from alcohol than alcohol dependent individuals without a history of past alcohol withdrawal episodes. The kindling effect leads to persistent functional changes in brain neural circuits as well as to gene expression.[58] Kindling also results in psychological symptoms of alcohol withdrawal becoming more intensified.[56] |
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