Pharmacodynamics and pharmacokinetics of parenteral histamine (H2)-receptor antagonists

Parenteral histamine (H2)-receptor antagonists are frequently used to prevent upper gastrointestinal bleeding caused by stress-induced gastric mucosal damage in critically ill patients. It is generally agreed that the goal of therapy in this syndrome is the consistent elevation of gastric pH levels above a certain value, often set at 4, in order to prevent the underlying mucosal damage from progressing to bleeding. The three H2-receptor antagonists currently available in a parenteral form and suitable for this mode of prophylaxis are cimetidine, ranitidine, and famotidine. The pharmacodynamic and pharmacokinetic properties of these agents, as they relate to their use in prevention of stress ulceration bleeding, are discussed here. These agents are more noted for their pharmacodynamic and pharmacokinetic similarities in acid suppression, elimination, and metabolism than for their differences. Ranitidine and famotidine are more potent than cimetidine, and famotidine has a slightly longer half-life than do cimetidine and ranitidine, but current dosing recommendations take these differences into account so that the agents have equivalent efficacy. Cimetidine and ranitidine have been widely used in this application. Less experience has been obtained, to date, with famotidine. Recent studies with primed, continuous infusions of cimetidine indicate that dosing schedule may be the key to obtaining better efficacy in prophylaxis of stress-related mucosal damage. Similar studies with ranitidine have not yielded results as promising as those with cimetidine, however, and few data are available on famotidine.