Pharmacological methods for the prevention of first and recurrent bleeding from esophagogastric varices

Drug candidates for the prevention of first and recurrent variceal bleeding include 1) vasoconstrictors, 2) vasodilators and 3) various drugs increasing lower esophageal sphincter pressure. 1) Nonselective and beta 2-selective beta-adrenergic blockers act through vasoconstriction at the level of the splanchnic arterioles, which adds to the effect of decreased cardiac output. Nonselective beta-blockers decrease portal pressure in most but not all patients by about 10-15%. Azygos venous blood flow, however, is decreased up to 40% in virtually all patients. Data on the efficacy of the nonselective beta-blocker propranolol in the prevention of recurrent variceal hemorrhage derived from prospective, placebo-controlled clinical trials are controversial. While one study showed a decrease in both rebleeding rates and long-term mortality in alcoholic cirrhotics with good liver function, these positive results were not confirmed by several subsequent trials. It has been argued that this discrepancy might be the consequence, at least in part, of differences in patient selection. In contrast, three randomized trials did not show any difference in rebleeding rates and survival between propranolol and endoscopic sclerotherapy thus indicating that propranolol might be useful for the prevention of variceal rebleeding. Preliminary results of placebo-controlled trials of propranolol and nadolol for the primary prophylaxis of variceal bleeding also suggest a potential role for beta-blockers in the treatment of portal hypertension. 2) Vasodilator candidates in the treatment of portal hypertension are nitrates, calcium channel blockers, serotonin antagonists, peripheral alpha-adrenergic blockers like prazosine and central alpha-stimulators such as clonidine. The action of nitrates is most probably mediated by reflex splanchnic vasoconstriction consequent on peripheral systemic vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)