H2-Receptor antagonists include cimetidine, famoti-dine, nizatidine, and ranitidine (Table 17–2). These agents competitively inhibit histamine binding to H2 receptors, thereby reducing gastric acid output and raising gastric pH.
All H2-receptor antagonists are equally effective in the treatment of peptic duodenal and gastric ulcers, hypersecretory states (Zollinger–Ellison syndrome), and gastroesophageal reflux disease (GERD). Intravenous preparations are also used to prevent stress ulceration in critically ill patients. Duodenal and gastric ulcers are usually associated with Helicobacter pylori infection, which is treated withcombinations of bismuth, tetracycline, and metronidazole. By decreasing gastric fluid volume and hydrogen ion content, H2 blockers reduce theperioperative risk of aspiration pneumonia. These drugs affect the pH of only those gastric secretions that occur after their administration.
The combination of H1- and H2-receptor antagonists provides some protection against drug-induced allergic reactions (eg, intravenous radio-contrast, chymopapain injection for lumbar disk disease, protamine, vital blue dyes used for sentinel node biopsy). Although pretreatment with these agents does not reduce histamine release, it may decrease subsequent hypotension.
Rapid intravenous injection of cimetidine or raniti-dine has been rarely associated with hypotension, bradycardia, arrhythmias, and cardiac arrest. These adverse cardiovascular effects have been reported following the administration of cimetidine to criti-cally ill patients. In contrast, famotidine can be safely injected intravenously over a 2-min period. H2-Receptor antagonists change the gastric flora by virtue of their pH effects. Complications of long-term cimetidine therapy include hepatotoxicity (ele-vated serum transaminases), interstitial nephritis (elevated serum creatinine), granulocytopenia, and thrombocytopenia. Cimetidine also binds to andro-gen receptors, occasionally causing gynecomastia and impotence. Finally, cimetidine has been asso-ciated with changes in mental status ranging from lethargy and hallucinations to seizures, particularly in elderly patients. In contrast, ranitidine, nizatidine, and famotidine do not affect androgen receptors and penetrate the blood–brain barrier poorly.
As a premedication to reduce the risk of aspira-tion pneumonia, H2-receptor antagonists should be administered at bedtime and again at least 2 h before surgery (Table 17–2). Because all four drugs are eliminated primarily by the kidneys, the dose should be reduced in patients with significant renal dysfunction.
Cimetidine may reduce hepatic blood flow and binds to the cytochrome P-450 mixed-function oxidases. These effects slow the metabolism of a multitude of drugs, including lidocaine, propranolol, diazepam, theophylline, phenobarbital, warfarin, and phenyt-oin. Ranitidine is a weak inhibitor of the cytochrome P-450 system, and no significant drug interactions have been demonstrated. Famotidine and nizatidine do not appear to affect the cytochrome P-450 system.
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