Continuous prazosin administration in cirrhotic patients: effects on portal hemodynamics and on liver and renal function.
ABSTRACT Hepatic vascular resistance is influenced by alpha-adrenergic tone. The aim of this study was to investigate the effects of continuous blockade of alpha-adrenoceptors with prazosin on hemodynamics, liver function, and renal function and whether the association of propranolol or furosemide enhances the portal pressure lowering effect of prazosin.
Cirrhotic patients with portal hypertension were studied at baseline and after a 3-month course of prazosin (n = 18) or placebo (n = 10).
No changes were observed in the placebo group. Prazosin decreased the hepatic venous pressure gradient (HVPG) while increasing hepatic blood flow. Liver function improved as shown by an increase in hepatic and intrinsic hepatic clearances of indocyanine green and galactose elimination capacity. A significant reduction in mean arterial pressure and systemic vascular resistance was associated with increases in plasma renin activity and aldosterone concentration and a decrease in glomerular filtration rate. The plasma volume increased significantly, and 6 patients developed edema. The association of propranolol (n = 8) but not furosemide (n = 7) to prazosin increased the reduction in HVPG and attenuated the increase in plasma renin activity.
In cirrhotic patients, continuous prazosin administration reduces portal pressure and improves liver perfusion and function but favors sodium and water retention. The association of propranolol enhances the decrease in portal pressure, suggesting a potential benefit from this combined therapy.
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ABSTRACT: Progress in the knowledge of the pathophysiology of portal hypertension has disclosed new targets for therapy, resulting in a larger spectrum of drugs with a potential role for clinical practice. This review focuses on pharmacologic treatments already available for reducing portal pressure and summarizes drugs currently under investigation in this field.Clinics in liver disease 05/2014; 18(2):303-317.
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ABSTRACT: Background and AimAcute-on-chronic liver failure (ACLF) is characterized by acute deterioration of cirrhosis, systemic inflammation and multiorgan failure. Inflammation is also key to the pathobiology of portal hypertension. This study aims to define the relationship between systemic and hepatic hemodynamics in patients with ACLF.Methods Sixty-patients with alcoholic cirrhosis were prospectively enrolled; stable cirrhosis (SC, n=27), acute decompensation without ACLF (AD, n=14) and ACLF (n=19) and managed with standard therapy. Systemic and hepatic hemodynamic studies were performed, and patients were followed for 3 months. Plasma norepinephrine, cytokine profile, nitrate/nitrite and malondialdehyde levels were measured.ResultsThree-month mortality was: SC-none; AD-14%; ACLF-47.2% (p<0.001). Mean arterial pressure was lowest in the ACLF group (p<0.001). ACLF patients had significantly higher hepatic vein pressure gradient (HVPG) whilst the hepatic blood flow was markedly reduced with an increase in intrahepatic resistance, which predicted mortality (AUROC: 0.87, P<0.0001). In ACLF, the severity of intrahepatic resistance correlated with markers of inflammatory response, norepinephrine levels, creatinine levels and severity of encephalopathy. Modeling data showed that the high norepinephrine levels in ACLF may contribute to the right shift of the HVPG-hepatic blood flow relationship and its levels correlated with inflammatory markers and mortality (AUROC: 0.90; p<0.0001).Conclusions The disturbances in systemic and hepatic hemodynamics in alcohol-related ACLF are associated with dysregulated inflammation, multiorgan failure and marked activation of the sympathetic nervous system. These abnormalities predict high mortality rates in alcohol-related ACLF patients.This article is protected by copyright. All rights reserved.Liver international: official journal of the International Association for the Study of the Liver 04/2014; · 3.87 Impact Factor
- Chemico-biological Interactions - CHEM-BIOL INTER. 01/2002; 2002(5):211-216.