Haemodynamic effects of acute and chronic administration of low-dose carvedilol, a vasodilating beta-blocker, in patients with cirrhosis and portal hypertension.
BACKGROUND
Carvedilol is a non-selective vasodilating beta-blocker with weak alpha1 receptor antagonism. Recent studies have demonstrated its potential as a portal hypotensive agent.


OBJECTIVE
To assess the haemodynamic effects and patient tolerability of the acute and chronic administration of low-dose carvedilol.


METHODS
Haemodynamic measurements were performed in ten cirrhotic patients before and 1 h after the administration of 12.5 mg oral carvedilol. The study was repeated 4 weeks after daily administration of 12.5 mg carvedilol.


RESULTS
After acute administration of carvedilol, there was a 23% reduction in the hepatic venous pressure gradient from 16.37 +/- 2.14 to 12.56 +/- 3.91 mmHg (P < 0.05), with significant falls in the heart rate, mean arterial pressure and cardiac output. Chronic administration resulted in a further fall in the hepatic venous pressure gradient from a baseline of 16.37 +/- 0.71 to 9.27 +/- 1.40 mmHg (P < 0.001) with the mean arterial pressure being unaffected. The drug was well tolerated with only one patient experiencing asymptomatic hypotension.


CONCLUSIONS
The results show that low-dose carvedilol is an extremely potent portal hypotensive pharmacological agent, and is worthy of further investigation in large randomized trials to assess its effect in preventing variceal haemorrhage.
Tripathi
D
D
Liver Unit, Department of Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK. d.tripathi@ed.ac.uk
Therapondos
G
G
Lui
H F
HF
Stanley
A J
AJ
Hayes
P C
PC
D002227:Carbazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D004334:Drug Administration Schedule; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006975:Hypertension, Portal / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D007677:Kidney Function Tests; D008099:Liver / Q000098:blood supply / Q000187:drug effects; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol