Part VIII. Folic acid antagonists

Cirrhosis Caused by Methotrexate in the Treatment of Psoriasis

“…Recently, nephrotoxicity has been reported.18 Leukemogenesis and damage to the posterior col¬ umns of the spinal cord also have been suggested as possible side effects but have not been documented satisfactorily. 1 The mechanism of the toxicity in liver is believed to differ from that of rapidly divid¬ ing cells, because the folinic acid stores of the liver are enormously larger than those of other tissues and folie acid reductase is not critical to the economy of the hepatic cell 11,19 However, Hersh and co-workers3 have suggested that the decreased synthesis of nucleic acid, amino acids, and protein could cause damage to the organelles and plasma membranes of hepatic parenchymal cells and that the hepatic injury was a direct toxic action of the drug since most patients could be affected and the reaction was dose dependent. The intracellular site of action was postulated to be different from those drugs causing intrahepatic cholestasis since bilirubinemia is rarely seen in methotrexate-induced hepatic toxicity.…”