Portal Hypertension Medication

Updated: Nov 30, 2017
  • Author: Jesus Carale, MD; Chief Editor: BS Anand, MD  more...
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Medication

Medication Summary

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.

The main advantages to using vasoactive agents include the ability of these drugs to treat variceal bleeding in the emergency department, lower portal pressure, and offer the endoscopist a clearer view of varices because of less active bleeding. Vasoactive agents represent an ideal treatment for sources of portal hypertensive bleeding other than esophageal varices (eg, gastric varices >2 cm below the gastroesophageal junction or portal hypertensive gastropathy). [8, 15]

The vasoconstrictors somatostatin and octreotide are used to treat acute bleeding in patients with portal hypertension before performing endoscopy. [47, 51] Intravenous infusions of octreotide will lower portal blood pressure and can prevent rebleeding during the patient's initial hospitalization. Vasodilators such as isosorbide mononitrate (ISMN) reduce intrahepatic vascular resistance without decreasing the peripheral or portal-collateral resistance.

Beta-blockers, which include propranolol, nadolol, and timolol, are used to provide primary and secondary prophylaxis. 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.

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Somatostatin Analogs

Class Summary

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. It has effects similar to those of vasopressin but does not cause coronary vasoconstriction. Somatostatin has an initial half-life of 1-3 minutes and is rapidly cleared from the circulation.

Somatostatin analogs inhibit the secretion of hormones involved in vasodilation. Octreotide is a synthetic octapeptide. Compared with somatostatin, octreotide has similar pharmacologic actions with greater potency and longer duration of action. In the US, octreotide is used off-label for the management of variceal hemorrhage. [47]

Octreotide (Sandostatin)

Octreotide, a synthetic octapeptide, acts primarily on somatostatin receptor subtypes II and V. It inhibits growth hormone secretion and has a multitude of other endocrine and nonendocrine effects, including the inhibition of glucagon, vasoactive intestinal peptide, and GI peptides. Octreotide has greater potency and a longer duration of action than somatostatin.

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Beta-Blockers, Nonselective

Class Summary

Nonselective beta-blocking agents decrease hepatic arterial and portal venous perfusion. Beta-adrenergic blockers may block the effect of vasodilators, decrease platelet adhesiveness and aggregation, and increase the release of oxygen to tissues.

Nonselective beta-blockers have been shown to prevent bleeding in more than 50% of patients with medium or large varices. [8] These agents exert a moderate effect on the reduction of portal flow, and smaller effects on the increase in portal resistance and decrease on portal pressure.

Propranolol is used off-label for primary prophylaxis — in combination with endoscopic variceal ligation (EVL) — for esophageal varices. This agent is also indicated for secondary prophylaxis for esophageal varices.

Propranolol (Inderal, InnoPran XL)

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 receptors in the heart and vascular smooth muscles.

Nadolol (Corgard)

Nadolol is a noncardioselective beta-blocker that reduces portal pressure through the reduction of portal and collateral blood flow.

Timolol

Timolol is a noncardioselective beta-blocker that reduces portal pressure through the reduction of portal and collateral blood flow.

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Vasopressin-Related

Class Summary

Vasoconstrictors reduce portal blood flow and/or increase resistance to variceal blood flow inside the varices. Therefore, these drugs reduce blood flow in the gastroesophageal collaterals because of their vasoactive effects on the splanchnic vascular system. When used in combination with nitrates, the efficacy and safety of vasoconstrictors have been shown to improve. However, their use may be limited as the risk of adverse events is higher with combination therapy.

In the US, vasopressin is used off-label for the management of acute variceal bleeding.

Terlipressin is widely used in Europe but has not received FDA approval for use in the United States. This is a synthetic analogue of vasopressin. It is the only pharmacologic agent shown to reduce mortality from variceal bleeding. Terlipressin has longer biologic activity than vasopressin. It significantly reduces portal and variceal pressure and azygos flow. The drug is beneficial when combined with sclerotherapy. Terlipressin also has the advantage of preserving renal function, which is a particularly important feature in patients with cirrhosis.

Vasopressin (Pitressin)

Vasopressin has vasopressor and antidiuretic hormone (ADH) activity. It increases water resorption at the distal renal tubular epithelium (ADH effect) and promotes smooth muscle contraction throughout the vascular bed of the renal tubular epithelium (vasopressor effects). However, vasoconstriction is also increased in the splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels. Vasopressin decreases the portal pressure in portal hypertension.

A notable adverse effect of this agent is coronary artery constriction, which may dispose patients with coronary artery disease to cardiac ischemia. This can be prevented with the concurrent use of nitrates. Vasopressin is rarely used.

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Vasodilators

Class Summary

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.

Nitrates, however, technically work by decreasing resistance. They decrease portal flow by decreasing mean arterial pressure. Oral nitroglycerin is used off-label for the management of variceal bleeding.

Nitroglycerin PO (Nitro-Bid, Nitrostat, Nitro-Time)

Nitroglycerin causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. The result is a decrease in blood pressure.

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