Effect of carvedilol on portal hypertension depends on the degree of endothelial activation and inflammatory changes

Brůha, Radan; Vı́tek, Libor; Petrtýl, J; Leníček, Martin; Urbánek, Petr; Zelenka, Jaroslav; Jáchymová, M; Svestka, T; Kaláb, M; Dousa, Miroslav; Marecek, Z

doi:10.1080/00365520600780403

Cited by 15 publications

(19 citation statements)

References 41 publications

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“…[19][20][21][22][23][24][25][26][27][28] Most of these studies assessed the effects of carvedilol on HVPG. The results show that carvedilol causes dose-related and marked decreases in HVPG (of about 20% from baseline), significantly greater than those caused by propranolol.…”

Section: Carvedilolmentioning

confidence: 99%

“…19 Figures in studies in patients with cirrhosis are 8%-13%. [19][20][21][22][23][24][25][26][27][28] As with all nonselective beta-blockers, carvedilol is contraindicated in patients with marked bradycardia, the sick sinus syndrome, and partial or complete heart block (unless a pacemaker is in place). Thus, an electrocardiogram is mandatory before starting therapy.…”

Section: Monitoring For Drug-related Adverse Eventsmentioning

confidence: 99%

“…19,20,27 During titration, the patient should be specifically asked for drugrelated adverse events (edema, dizziness, bradycardia, hypotension, nausea, blurred vision). The dose should not be increased in patients developing symptoms or with a systolic blood pressure <90 mm Hg or a heart rate <50 bpm.…”

Section: Monitoring For Drug-related Adverse Eventsmentioning

confidence: 99%

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Carvedilol for Portal Hypertension in Patients With Cirrhosis

Bosch

2010

Hepatology

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A 48-year-old male with hepatitis C-related cirrhosis is found on endoscopy to have large esophageal varices with red signs. He has never previously had variceal bleeding, and there is no evidence of hepatic encephalopathy. He does have mild ascites. Comorbidity includes diabetes which has been present for many years and is well-controlled on a stable dose of insulin. He has no cardiopulmonary disease. The hemoglobin is 12.4 g/dL, white blood cell count is 6800/mm 3 , and platelets are 112 Â 10 9 /L. Serum bilirubin is 1.8 mg/ dL, creatinine is 1.2 mg/dL, international normalized ratio is 1.3, and the serum albumin is 3.5 g/dL. The electrocardiogram and chest x-ray are normal. The ultrasound examination does not show portal vein thrombosis or hepatocellular carcinoma.What is the role of carvedilol in the prevention of variceal bleeding in this patient? How will the dose of carvedilol be adjusted and how is the patient to be monitored for adverse drug events? When would carvedilol be preferred over nadolol or propranolol? Would the approach be different if the patient was of Child-Pugh class C cirrhosis? The ProblemPortal hypertension is an almost unavoidable complication of cirrhosis, and provides the driving force for most of its complications, such as esophageal and gastric varices, variceal bleeding, portal hypertensive gastropathy, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, thrombopenia, leukopenia and anemia, and portal-systemic encephalopathy.1 Recent studies have shown that for these complications to develop, the portacaval pressure gradient-evaluated clinically by the hepatic venous pressure gradient (HVPG)-should increase above 10 mm Hg and should be above 12 mm Hg for variceal bleeding. 2,3The prevalence of varices is about 40% in asymptomatic compensated patients.2 Development of varices follows an incidence of approximately 6% per year. The incidence is nearly double in patients with a baseline HVPG >10 mm Hg, who therefore represent a high-risk group.2 These patients are also at higher risk of developing decompensation (ascites, bleeding, jaundice, encephalopathy) and hepatocellular carcinoma. 4,5 Because of this, there is a great interest in strategies to revert portal hypertension, since these would prevent portal hypertension-related complications, clinical decompensation, and death. The benefit of reduction of HVPG has actually been proven for patients exhibiting a ''good hemodynamic response'' to nonselective beta-adrenergic blockers; i.e., those who exhibit a decrease in HVPG > 20% of baseline or to values below 12 mm Hg during continued therapy, 6,7 or who show a decrease in HVPG >10% of baseline 20 minutes after an intravenous infusion of propranolol. 8,9 Besides the increased intravascular pressure, the risk of bleeding from varices is further influenced by other factors, such as the diameter of the varices and the thickness of the variceal wall.10 These factors are interrelated by Laplace's law in the concept of wall tension (t), according to which: t ¼ variceal tran...

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Section: Carvedilolmentioning

confidence: 99%

Section: Monitoring For Drug-related Adverse Eventsmentioning

confidence: 99%

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Carvedilol for Portal Hypertension in Patients With Cirrhosis

Bosch

2010

Hepatology

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“…Carvedilol is a 3rd-generation nonselective beta blocker with vasodilating properties, owing principally to alpha1 blockade [14]. It has no intrinsic sympathomimetic activity and has some antioxidant properties characterized by membrane stabilization [14].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Apatinib on the Metabolism of Carvedilol Both in vitro and in vivo

Lin

Wang²,

Li³

et al. 2015

Pharmacology

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Background: In light of the growing number of cancer survivors, the incidence of cardiovascular complications in these patients had also increased, while the effect of apatinib on the pharmacokinetic of cardioprotective drug (carvedilol) in rats or human is still unknown. The present work was to study the impact of apatinib on the metabolism of carvedilol both in vitro and vivo. Methods: A specific and sensitive ultra-performance liquid-chromatography tandem mass spectrometry method was applied to determine the concentration of carvedilol and its metabolites (4′-hydroxyphenyl carvedilol [4′-HPC], 5′-hydroxyphenyl carvedilol [5′-HPC] and o-desmethyl carvedilol [o-DMC]). Results: The inhibition ratios in human liver microsomes were 10.28, 10.89 and 5.94% for 4′-HPC, 5′-HPC and o-DMC, respectively, while in rat liver microsomes, they were 3.22, 1.58 and 1.81%, respectively. The data in vitro of rat microsomes were consistent with the data in vivo that the inhibition of 4′-HPC and 5′-HPC formation was higher than the control group. Conclusion: Our study showed that apatinib could significantly inhibit the formation of carvedilol metabolites both in human and rat liver microsomes. It is recommended that the effect of apatinib on the metabolism of carvedilol should be noted and carvedilol plasma concentration should be monitored.

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“…Currently, several treatment modalities are commonly employed for the management of LC-induced PHT, including systemic drug treatment, surgical intervention, endoscopic ligation, and liver transplantation. Although endoscopic ligation is useful in preventing initial hemorrhage in the upper digestive tract, it is less effective when dealing with recurring bleeding [1] . Transjugular intrahepatic portosystemic stent shunt (TIPSS) can, to a certain extent, reduce various complications of PHT.…”

Section: Introductionmentioning

confidence: 99%

Attenuation of portal hypertension by natural taurine in rats with liver cirrhosis

Liang¹,

Deng²,

Lin³

et al. 2009

WJG

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AIM:To investigate the inhibitory effect of natural taurine (NTau) on portal hypertension (PHT) in rats with experimentally-induced liver cirrhosis (LC). METHODS:Experimentally-induced LC Wistar rats (20 rats/group) were treated with either oral saline or oral NTau for 6 consecutive weeks. Evaluation parameters included portal venous pressure (PVP), portal venous resistance (PVR), portal venous flow (PVF), splanchnic vascular resistance (SVR) and mean arterial pressure (MAP). Vasoactive substance levels including nitric oxide (NO), nitric oxide synthase (NOS) and cyclic guanosine monophosphate (cGMP) were also measured. Histological investigation of type Ⅰ and Ⅲ collagen (COL Ⅰ and Ⅲ) and transforming growth factor-β1 (TGF-β1) was also performed. RESULTS:

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Effect of carvedilol on portal hypertension depends on the degree of endothelial activation and inflammatory changes

Abstract: Markers of systemic inflammation and endothelial dysfunction seem to predict the hypotensive effect of carvedilol on portal hypertension in patients with liver cirrhosis and may be useful in the assessment of the efficacy of the therapy.

Cited by 15 publications

References 41 publications

Carvedilol for Portal Hypertension in Patients With Cirrhosis

Carvedilol for Portal Hypertension in Patients With Cirrhosis

The Effect of Apatinib on the Metabolism of Carvedilol Both in vitro and in vivo

Attenuation of portal hypertension by natural taurine in rats with liver cirrhosis

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