Reductions in portal pressure by selective beta 2‐adrenoceptor blockade in patients with cirrhosis and portal hypertension.

Abstract

1 In order to elucidate the mechanisms by which 18-adrenoceptor blockade leads to a reduction in portal pressure, we have measured portal pressure, heart rate and cardiac index in 17 patients with cirrhosis and portal hypertension following the oral administration of the selective ,82-adrenoceptor blocking agent, ICI 118551, in the two dosage ranges 10-20 mg and 50-100 mg. 2 There was a fall in portal pressure in 14 of the 17 patients from a median of 17 mm Hg to a median of 15 mm Hg, P < 0.01, that occurred only at 60 min following administration of the drug. 3 Although there were early systemic haemodynamic changes, with a significant fall in heart rate and cardiac index from before to 30 min after the ingestion of ICI 118551 (median heart rates 86 and 80 beats/min respectively, P < 0.01, median cardiac indices 3.5 and 3.3 1 min-' m-2, P < 0.05), these occurred before the fall in portal pressure and were unrelated to changes in portal pressure. 4 This reduction in portal pressure independent of systemic haemodynamic changes is consistent with 132-adrenoceptor blockade within the splanchnic and hepatic arterial circulations; subsequent increases in splanchnic and hepatic arterial resistances with a concomitant fall in portal blood flow and hepatic portal resistance may lead to the reduction in portal pressure.

A drug therapy for the prevention of variceal haemorrhage

“…ICI 11855 is a selective β 2 antagonist, which was studied by Bihari et al . in 17 patients 38 . There was a significant reduction in the portal pressure 60 min following administration of the drug, which was accompanied by significant reductions in the heart rate and cardiac index, both of which were not related to the fall in the portal pressure.…”

Beta‐blockers in portal hypertension: new developments and controversies

“…However, one trial has demonstrated no advantage of metoprolol over placebo in preventing gastrointestinal bleeding . Selective beta 2 blockade offers no advantage over propranolol, and has the potential to reduce hepatic blood flow to a greater degree .…”

Drug classification for patients with comorbidities

“…Decompensation of cirrhosis is prevented by nonselective β-blockers (nadolol, propranolol, and carvedilol) which are recommended for the primary and secondary prevention of bleeding [ 2 , 3 ]. The beta1-blockers and isosorbide mononitrate can reduce portal pressure [ 4 ]. Statins are associated with a lower risk of hepatic decompensation and mortality in patients with chronic liver diseases and liver cirrhosis [ 5 , 6 ].…”