What are the possible mechanisms involved in the occurrence of tolerance to chronic alcohol intake?

• Tolerance may result from ethanol-induced up-regulation of a pathway in response to the continuous presence of ethanol. GABA neurotransmission is believed to play a significant role in tolerance and withdrawal because sedative-hypnotic drugs that enhance GABAergic neurotransmission are able to substitute for alcohol during alcohol withdrawal, and  there is
  evidence of down-regulation of GABAA-mediated responses with chronic alcohol exposure.

What are the toxic effects of chronic alcohol consumption on the liver and hepatic metabolism?

• Chronic alcohol consumption leads to a progressive decline in liver function, which may progress to alcoholic hepatitis, liver cirrhosis and liver failure. Gluconeogenesis is decreased, resulting in hypoglycemia and fat accumulation. there is also and increase in the activity of liver microsomal enzyme.

What is Wernicke-Korsakoff-syndrome and how is it treated?

• Paralysis of the external eye muscles, ataxia, and a confused state that can progress to coma
  and death. It is associated with thiamine deficiency but is rarely seen in the absence of alcoholism.
• Treated with parenteral thiamine.

Fully explain the fetal alcohol syndrome.

• Teratogenic effects associated with chronic maternal alcohol abuse during pregnancy .The abnormalities that have been characterized as fetal alcohol syndrome include intrauterine growth retardation, microcephaly, poor coordination, underdevelopment of midfacial region (appearing
  as a flattened face), and minor joint anomalies. More severe cases may include congenital heart defects and mental retardation.

How do the pharmacokinetic interactions of acute alcohol consumption differ from that of chronic alcohol consumption?

• Chronic alcohol consumption enhance the metabolic biotransformation of other drugs  e.g paracetamol. acetaminophen. Chronic consumption of three or more drinks per day increases the risk of hepatotoxicity due to toxic or even high therapeutic levels of acetaminophen as a
  result of increased P450-mediated conversion of acetaminophen to reactive hepatotoxic metabolites.
• Acute alcohol use can inhibit metabolism of other drugs because of decreased enzyme activity or decreased liver blood flow e.g  Phenothiazines, tricyclic antidepressants, and sedative
  hypnotics. 

Name 4 drug interactions with alcohol where the pharmacological effects of the other drugs are potentiated by alcohol.

• Visodilators
• Oral hypoglycemic agents
• Sedative hypnotics
• Anti-depressants