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

Consumption of alcohol over long periods of time can cause both physical and psychological dependence. The more you consume alcohol, the higher your tolerance to it becomes, so you would have to keep consuming more and more of it to reach the same stimulating CNS effects. 

Tolerance results from ethanol-induced up-regulation of a pathway in response to the continuous presence of ethanol. Dependence can result from over-activity of that same pathway after the ethanol effect disappears and before the system has time to return to a normal ethanol-free state. 

GABA neurotransmission plays an important role in tolerance as well as in alcohol 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 GABA-mediated responses with chronic alcohol exposure. 

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

Liver disease is one of the most common toxic side effects of excessive alcohol consumption, 15-30% of chronic drinkers eventually develop liver disease. Alcoholic fatty liver (a reversible condition) may progress to alcoholic hepatitis and the finally to liver cirrhosis and liver failure. 

Women are more susceptible to hepatotoxicity than men. Concurrent infection with hepatitis B or C virus increases the risk of severe liver disease. Cirrhosis contributes to elevated portal blood pressure and esophageal and gastric venous varices. These varices may rupture and result in massive bleeding. 

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

Wernicke-Korsakoff-syndrome is characterized by 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. Patients who suspect they have this syndrome must receive thymine therapy. 

Often, the ocular signs, ataxia, and confusion improve after administration of thymine. But, most patients are left with a chronic disabling memory disorder known as Korsakoff's psychosis. 

Fully explain the fetal alcohol syndrome

Chronic maternal alcohol abuse during pregnancy is associated with teratogenic effects, and alcohol is the main cause of mental retardation and congenital malformation. 

The abnormalities that have been characterized as fetal alcohol syndrome include:

1. Intrauterine growth retardation
2. microcephaly
3. Poor coordination
4. Under development of midfacial region (appears as a flattened face)
5. Minor joint abnormalities

In more severe cases, congenital heart defects and mental retardation. 

Ethanol rapidly crosses the placenta and reaches concentrations in the fetus that are similar to that in the maternal blood. The fetal liver has no alcohol dehydrogenase activity, so the fetus relies solely on maternal and placental enzymes for the elimination of alcohol. Alcohol triggers apoptotic neurodegeneration. 

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

Chronic alcohol consumption differs from that of acute alcohol consumption in the following way: chronic alcohol consumption increases the metabolic transformation of other drugs whereas acute alcohol consumption decreases the metabolic transformation of other drugs. 

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

Phenothiazines (eg: promazine), tricyclic anti-depressants (eg: amitriptyline), sedative-hypnotics (eg: zaleplon) and vasodilators (eg: enalapril). 

Bertram G. Katzung. (2018). The Alcohols. In: Bertram G. Katzung Basic & Clinical Pharmacology. New York: Mc Graw-Hill Education. 396-408.