Side effects of cimetidine.

Cimetidine, an H2 receptor antagonist, is widely used in the treatment of duodenal ulcer, ZollingerEllison Syndrome (Binder et al., 1978; Winship, 1978; Ippoliti et al., 1978; Gray et al., 1978; Lc Canthy, 1978) benign gastric ulcer, gastric erosions and oesophagitis (Freston, 1979; Frost et al., 1977; Englert et al., 1978). In human beings it has a circulating half life of disappearance of 123±12 min (Burland et al., 1975). Complete absorption occurs on oral ingestion, in 80-90 min. Seventy percent is excreted in urine (Regan et al., 1977), 10% in stool (Griffiths, 1977) and inactivated mainly by the liver (Griffiths et al., 1977). Its main toxic effects are due to its action on widely distributed H2 receptors, or due to idiosyncrasy, in some instances, mechanism of side effects is not well understood. Hepatotoxic effect are slight rise in serum transaminases (<100 mu/ml) without any signs of hepatic dysfunction, focal necrosis and cholestastis reported in 5 children by Spence et al (1977), who observed higher levels of Cimetidine in bile than in portal or systemic venous blood implying active transport of drug from portal blood to hepatic bile. Effect of Cimetidine on fasting serum gastrin levels is not well established (Bank et al., 1977; Richardson, 1978). Rebound in acid secretion or ulcer activity after discontinuance of Cimetidine is not known (McGuigon, 1981) and if given for longer duration effectively reduces frecmency of ulcer recurrences (Blackwood et al., 1978). Cimetidine is recommended in treatment of benign gastric ulcer and not in malignant (Elder et al., 1979) where its role is debatable. Nitrosa-tion of the drug has been observed in vitro (McGuigon, 1981) but whether it occurs in vivo and these nitrosated compounds are carcinogenic in experimental animals or in human beings is not well established. Marked structural similarity has been reported by Elder et al (1979) between these potential nitroso derivatives of Cimetidine and N-Methyl N-Nitroso-Nniotrosoguanidine (MNNG) which in some species behaves as direct local acting gastric carcinogen (Sugimura and Fujimura 1967). Vitamin B 12 malabsorption by Cimetidine has not yet been observed (McGregor et al., 1977) probably