Enzyme induction ethanol causing

In animals, chronic ethanol causes induction of hepatic microsomal enzymes, and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoenzyme is important in the oxidative metabolism of paracetamol). This conclusion is not yet fully documented in man. 

Hepatic depletion of vitamin A stores is caused by chronic ethanol consumption (Bonjour, 1981). Night blindness suffered by alcoholics has been attributed to a low intake of vitamin A (McClain et aL, 1979). However, Sato and Lieber (1982) have demonstrated that ethanol depletes hepatic vitamin A stores in baboons and rats even when it is administered in combination with a nutritionally adequate diet. In addition, animals consuming ethanol in marginal diets were depleted more rapidly of vitamin A. No effect of ethanol intake on retinol binding protein or on serum vitamin A levels could be detected in these studies. Leo and Lieber (1982) found that hepatic vitamin A was depleted to one-fifth of normal levels in alcoholics with only moderate liver disease. Sato and Lieber (1982) observed that retinoic acid was more rapidly metabolized by the MFO system after chronic ethanol intake, and they postulated that vitamin A depletion was the result of MFO enzyme induction. 

A coal tar solution (crude coal tar diluted to 20% with ethanol and polysorbate 80) was applied to clinically unaffected skin of three patients with severe atopic dermatitis and six patients with generalized psoriasis (Bickers and Kappas 1978). Another skin area at least 10 cm away was not treated or was treated with 100 mL of the vehicle alone. Twenty-four hours later, a 6-mm punch biopsy was obtained from coal tar treated and control areas and the effect on AHH activity was determined. Application of coal tar to the skin caused induction of cutaneous AHH activity that varied from 2.4- to 5. 4-fold over the enzyme activity in untreated skin areas, suggesting absorption after topical application. 

Drug Interactions Barbiturates combine with other CNS depressants to cause severe depression ethanol is the most frequent offender, and interactions with first-generation antihistamines also are common. Isoniazid, methylphenidate, and monoamine oxidase inhibitors also increase the CNS-depressant effects. Other prominent drag interactions occin as a result of the induction of hepatic drug-metabolizing enzymes by barbiturates see above). 

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