The most important component of this therapeutic combination is the nonselective beta blocker. Recent data suggest that in patients with very compensated cirrhosis (ie, patients who have clinically significant portal hypertension but no or small varices), nonselective beta blockers can prevent clinical decompensation.
What is the best nonselective beta blocker for portal hypertension?
Another option is carvedilol, which is a nonselective beta blocker that also has an alpha-adrenergic vasodilating effect and causes a more marked reduction in portal pressure than traditional nonselective beta blockers.
How do beta blockers reduce portal pressure and hepatic venous pressure?
Consequently, they reduce portal pressure. In primary prophylaxis, beta blockers reduced the bleeding risk from 30 to 15%; in secondary prophylaxis, this risk decreased from 60 to 42% in the first year. Heart rate decrease does not necessary correlate with reduction in hepatic venous pressure gradient (HVPG).
Are non-selective beta-blockers effective for portal hypertension in liver cirrhosis?
Summary Non-selective beta-blockers (NSBBs) are the mainstay of treatment for portal hypertension in the setting of liver cirrhosis. Randomised controlled trials demonstrated their efficacy in preventing initial variceal bleeding and subsequent rebleeding.
How effective are beta blockers for primary and secondary prophylaxis?
In primary prophylaxis, beta blockers reduced the bleeding risk from 30 to 15%; in secondary prophylaxis, this risk decreased from 60 to 42% in the first year. Heart rate decrease does not necessary correlate with reduction in hepatic venous pressure gradient (HVPG).
Why do we use non selective beta-blockers in portal hypertension?
Non-selective beta blockers are very useful drugs in preventing first variceal bleeding and re-bleeding in patients with cirrhosis. These drugs work in two ways: 1) by blocking β1 receptors and reducing cardiac output, and 2) by blocking β2 receptors, producing splanchnic vasoconstriction and reducing portal flow.
Can selective beta-blockers be used for portal hypertension?
Reduction in portal pressure is greater with NSBB (propranolol, nadolol) than with selective beta-blockers because, as demonstrated experimentally, the main portal pressure–reducing effect stems from splanchnic vasoconstriction because of beta2-adrenergic blockade.
Which beta-blocker is best for portal hypertension?
Carvedilol is a new NSBB that is increasingly used; it has a greater portal pressure reducing effect than propranolol and is safe in patients with compensated and decompensated cirrhosis.
How do beta-blockers help portal hypertension?
By slowing the heart rate and widening the blood vessels, beta-blocker medicines such as propranolol and nadolol appear to lower the blood pressure in varices that bypass the liver. In people who have esophageal varices, beta-blockers have been shown to reduce the risk of having a first episode of bleeding.
Why are beta-blockers nonselective in cirrhosis?
Non selective beta-blockers (NSBBs) have been used for decades in patients with liver cirrhosis to reduce portal pressure and the risk for portal hypertensive bleeding (1-3). International guidelines recommend NSBB as primary and secondary prophylaxis for variceal bleeding in cirrhosis (4).
What is selective and nonselective beta-blockers?
Beta-1 selective blockers are preferred for therapy of heart disease, whereas the nonselective beta-blockers are preferred as therapy to prevent recurrent variceal hemorrhage in patients with cirrhosis and portal hypertension.
Which beta-blockers are non selective?
WHAT ARE NAMES OF NONSELECTIVE BETA-BLOCKERS?Betapace.Betapace AF.Blocadren (DSC)Corgard.Hemangeol.Inderal.Inderal LA.Innopran XL.More items...•
Why is propranolol used for portal hypertension?
Propranolol, a nonselective β blocker, has been shown to be effective for the prevention of variceal bleeding and rebleeding, and is widely used as the pharmacotherapy for the treatment of portal hypertension in patients with cirrhosis.
How do beta-blockers help with variceal bleeding?
Beta blockers — Beta blockers, which are traditionally used to treat high blood pressure, are the most commonly recommended medication to prevent bleeding from varices. Beta blockers decrease pressure inside of the varices, which can reduce the risk of bleeding by 45 to 50 percent [1].
How does beta-blockers affect the liver?
Abstract. Drug-induced liver injury is a common cause of acute liver failure. β-blockers are a widely prescribed class of medications; however, hepatotoxicity is a rare adverse effect of this medication of which clinicians must be aware. This case suggests that hepatotoxicity may be a class effect of β-blockers.
Which beta-blockers are selective?
The cardio-selective beta-blockers include atenolol, betaxolol, bisoprolol, esmolol, acebutolol, metoprolol, and nebivolol.
How do beta-blockers help in cirrhosis?
Non-selective beta-blockers (NSBBs) are the mainstay of treatment for portal hypertension in the setting of liver cirrhosis. Randomised controlled trials demonstrated their efficacy in preventing initial variceal bleeding and subsequent rebleeding.
How does beta blocker work?
These drugs work in two ways: 1) by blocking beta1 receptors and reducing cardiac output, and 2) by blocking beta2 receptors, producing splanchnic vasoconstriction and reducing portal flow.
Do beta blockers reduce portal pressure?
Consequently, they reduce portal pressure. In primary prophylaxis, beta blockers reduced the bleeding risk from 30 to 15%; in secondary prophylaxis, this risk decreased from 60 to 42% in the first year. Heart rate decrease does not necessary correlate with reduction in hepatic venous pressure gradient (HVPG).
What is non-cardioselective beta blocker?
Non-cardioselective beta-blockers act in two principal ways to reduce portal pressure (Table 1 ). Firstly, there is beta 1 receptor blockade, which results in reduced cardiac output and splanchnic blood flow 22.
What causes portal hypertension?
The second event accounts for 20–30% of increased intrahepatic resistance to portal inflow. There is contraction of sinusoidal and perisinusoidal contractile cells [stellate cells and vascular smooth muscle cells (VSMCs)] with intrahepatic imbalance between vasoconstrictors (such as endothelin 1 and angiotensin) and vasodilators (such as nitric oxide and glucagon) 18. This imbalance leads to reduced intrahepatic eNOS activity. The third event is splanchnic vasodilatation in response to a relatively ischaemic liver or extrahepatic excess of NO, with sGC‐PKG signalling and smooth muscle cell relaxation 19. The result is increased portal blood flow, which maintains portal hypertension. These hemodynamic changes lead to the hyperdynamic circulation, which manifests as high cardiac output with low systematic vascular resistance and arterial hypotension 18. The second and third events are amenable to drug therapy.
Does timolol have a lower solubility than nadolol?
Timolol, like nadolol, has low lipid solubility and is less likely to result in central side effects. Timolol also has a greater affinity for both beta 1 and, particularly, beta 2 receptors than propranolol or nadolol 28. Theoretically, this characteristic could result in a greater reduction in portal pressure.
Can beta blockers reduce portal pressure?
There are many studies investigating the role of non-selective beta-blockers in portal hypertension. Satisfactory reduction in portal pressure is possible in a third to half of patients with propranolol and nadolol, although combining these drugs with nitrates may be more effective.
Does carvedilol reduce portal pressure?
Carvedilol can reduce portal pressure to a greater degree than propranolol, and is effective in primary and secondary prophylaxis 10 - 12 . Hepatic venous pressure gradient (HVPG) monitoring has a role predicting response to NSBB and long-term prognosis 13, 14.
What is the purpose of beta blockers?
Beta-blockers, which include propranolol, nadolol, and timolol, are used to provide primary and secondary prophylaxis. Beta-blockers lower the cardiac output (via blockade ...
What is the effect of beta blockers on the cardiac output?
Beta-blockers lower the cardiac output (via blockade of beta1 adrenoreceptors) and cause splanchnic vasoconstriction (via blockade of vasodilatory adrenoreceptors of the splanchnic circulation), reducing portal and collateral blood flow. Next: Somatostatin Analogs.
Why do vasoconstrictors reduce blood flow?
Therefore, these drugs reduce blood flow in the gastroesophageal collaterals because of their vasoactive effects on the splanchnic vascular system.
What is the role of propranolol in blood pressure?
Propranolol is a noncardioselective beta-blocker that reduces portal pressure through the reduction of portal and collateral blood flow. It competes with adrenergic neurotransmitters (eg, catecholamines) at sympathetic receptor sites. Similar to atenolol and metoprolol, propranolol blocks sympathetic stimulation mediated by beta1-adrenergic ...
How does a vasodilator affect the portal?
Vasodilators have been shown to exert a small effect on the reduction of portal flow, an increase in portal resistance, and decrease on portal pressure. These agents reduce intrahepatic vascular resistance without decreasing peripheral or portal-collateral resistance.
What are the goals of pharmacotherapy?
The goals of pharmacotherapy are to reduce mortality and morbidity, and prevent complications associated with acute bleeding related to portal hypertension. Two main categories of drugs, vasoconstrictors and vasodilators, are used.
Where does somatostatin come from?
Somatostatin, an orphan drug, is a naturally occurring tetradecapeptide isolated from the hypothalamus and from pancreatic and enteric epithelial cells. Through vasoconstriction, somatostatin diminishes blood flow to the portal system, thus decreasing variceal bleeding.
What is the mechanism of portal hypertension?
Moreover, there is intrahepatic resistance to this blood flow , the first known mechanism of portal hypertension. This is due not only to an alteration in hepatic architecture, but also to a dynamic situation originating in the contraction of perivascular smooth muscle cells, myofibroblasts, and hepatic stellate cells, which represent approximately 30% of global intrahepatic resistance, this concept first described by Bathal and Groszmann. 1 The previously mentioned mechanisms increase portal territory pressure. By employing hepatic vein pressure gradient (HVPG = wedged hepatic pressure-free hepatic pressure) as a portal pressure reflex, it is known that an HVPG of >10 mmHg is required for esophageal varices to appear, and an HVPG of over 12 mmHg is a requirement for these varices to bleed. 2
How do beta blockers work?
These drugs work in two ways: 1) by blocking β1 receptors and reducing cardiac output, and 2) by blocking β2 receptors, producing splanchnic vasoconstriction and reducing portal flow. Consequently, they reduce portal pressure. In primary prophylaxis, beta blockers reduced the bleeding risk from 30 to 15%; in secondary prophylaxis, this risk decreased from 60 to 42% in the first year. Heart rate decrease does not necessary correlate with reduction in hepatic venous pressure gradient (HVPG). When this gradient is reduced to less than 12 mmHg, the patient will not bleed; when this is reduced > 20% from basal values bleeding risk is extremely low, estimated at 9% at 2 years. The only way to know whether the patient has become a responder is to measure the HVPG. Additionally, by means of this method we also can identify the non-responders, who have a higher rate of re-bleeding, between 54 and 64%, and can attempt to utilize a more aggressive therapy, such as adding isosorbide mononitrate to the beta blocker or combining the beta blocker with endoscopic ligation. These options are discussed in the present review.
What is the role of propranolol in preventing variceal re-bleeding?
Propranolol and nadolol, which are non-selective beta blockers, reduce portal pressure via two mechanisms: 1) Cardiac output is reduced by blocking β1 adrenergic receptors, 2) Splachnic vasoconstriction by blocking β2 receptors (vasodilators). By means of these two mechanisms splanchnic flow is reduced, as is portal pressure, reflecting a reduction of pressure in collateral veins (varices) and also in their walls.
Is sclerotherapy a primary prophylaxis?
In primary prophylaxis, endoscopic sclerotherapy is not recommended due to the morbidity related with this procedure. A meta-analysis comparing endoscopic variceal ligation (EVL) vs beta blocker treatment 16 estimated an odds ratio (OR) for first bleeding episode of 0.48 (0.24 to 0.96), with a necessary number to treat (NNT) of 13 patients in favor of EVL, although it does not offer great advantages with regard to survival. Thus, EVL is not recommended as primary prophylaxis 17 at present. EVL should be considered for the patient who is unable to tolerate or does not respond to beta blocker therapy. Additionally, this meta-analysis has been criticized for including trials published only as summaries and also for including one trial in which number of patients who bled under beta blocker treatment was higher than in other reports; as if this were not sufficient, no cost analyses were included for EVL. In a new trial 18 in which 50 patients were randomized for banding and 50 for beta blocker therapy as primary prophylaxis, there was a bleeding frequency at 22 months of 10 patients (20%) for the first group and 16 patients (32%) for the second group (p = 0.23) without a difference in mortality. Future trials should focus on comparing EVL and beta blocker therapy with respect to survival and cost analysis. Preliminary data suggest that propranolol plus EVL is not better than banding alone in primary prophylaxis, 19 although it does reduce variceal recurrence. The same study published in an extended form 20 reported that both endoscopic banding plus propranolol and endoscopic banding alone are effective in primary prophylaxis of bleeding from high-risk varices. Addition of propranolol does not decrease the probability of first bleeding or death in patients on EVL; however, varices recurrence is lower if propranolol is added to EVL.