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

Chronic alcohol intake may result in tolerance and physical or psychological dependence. This may occur due to several mechanisms. This takes place through changes in the central nervous system adjustment due to constant exposure on receptors or secondary messengers as well as an increase in the rate of alcohol metabolism induced by the MEOS when chronic alcohol consumption occurs allowing for increased metabolism of ethanol and clearance of other drugs in the body that are eliminated by CYP450 enzymes.

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

Liver diseases such as Hepatitis, Cirrhosis and Liver failure may all result from the progressive decrease in liver function caused by chronic alcohol use. This tissue damage results from the direct effects of ethanol and acetaldehyde and having to process an increased load of active metabolites. The decrease in gluconeogenesis causes hypoglycaemia and fat accumulation, also nutrient deficiencies may contribute to the damage.

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

A unique syndrome that occurs because of neuropathy. It is characterized by paralysis of external eye muscles, ataxia and confusion which may lead to coma and death. This syndrome is associated with a thiamine(B1) deficiency therefore patients with chronic alcohol effects are administered thiamine therapy parenterally to prevent any permanent brain damage.

• Fully explain the foetal alcohol syndrome.

The chronic use of alcohol during pregnancy causes teratogenic effects that result in mental retardation and malformation of the foetus. This syndromes abnormality may be classified  by mental intrauterine growth retardation, microcephaly, poor coordination and the underdevelopment of the midfacial area and minor joint abnormalities. In extreme cases the foetus may develop congenital heart defects and mental retardation. Due to the pharmacokinetics of alcohol, it can cross over into the placenta and reach levels in the foetus that are like that in the mother’s blood which is rather dangerous for a foetus that is still developing.

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

Chronic alcohol use induces increased metabolism of alcohol and other drugs metabolised by CYP450. While acute alcohol consumption causes the effects of an opposite nature and thus reduces the metabolism processes.

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

Phenothiazines, TCA’s and sedative hypnotics like the benzodiazepine’s metabolism is decreased or inhibited under the influence of acute alcohol consumption due to a decrease in enzyme activity and liver blood flow. Vasodilating drugs and hypoglycaemic drugs effects are potentiated by acute alcohol consumption  result in extreme vasodilation throughout the body causing a drop in blood pressure leading to increased heart rates to maintain vital organ function. Alcohol increases the anti-platelet aggregation effects of aspirin.