What is the drug of choice for esophageal varices and portal hypertension, and what are the alternative drugs?

Drug Therapy for Esophageal Varices and Portal Hypertension

Terlipressin is the drug of choice for acute bleeding from esophageal varices due to portal hypertension, while non-selective beta-blockers (NSBBs) are the first-line therapy for prevention of bleeding. 1, 2

Acute Bleeding Management

• Vasoactive drugs are essential in acute variceal bleeding to reduce splanchnic blood flow and portal pressure 1
• Terlipressin (a synthetic vasopressin analog) is the preferred agent with the most convincing data for controlling acute variceal bleeding 1
  • Mechanism: Acts as a prodrug for lysine-vasopressin, reducing portal hypertension and increasing mean arterial pressure 3
  • Advantage: Longer half-life and fewer adverse effects compared to vasopressin 1
• Alternative vasoactive drugs for acute bleeding include:
  • Octreotide (somatostatin analog): Has a good safety profile and is as effective as vasopressin 1, 2
  • Somatostatin: Direct vasoconstrictor with good safety profile 1, 4
• Vasopressin is less preferred due to:
  • Short half-life requiring continuous IV infusion 1
  • Significant side effects including mesenteric or myocardial ischemia from systemic vasoconstriction 1, 4

Prevention of Variceal Bleeding

Primary Prevention (Before First Bleed)

• NSBBs are the first-line drug therapy for prevention of initial variceal bleeding 2, 5
  • Propranolol: Starting dose 20-40 mg orally twice daily, adjusted every 2-3 days until target heart rate of 55-60 beats per minute 2
  • Nadolol: Starting dose 20-40 mg orally once daily, adjusted to target heart rate 2
  • Carvedilol: May achieve better response rates than propranolol due to additional α-adrenergic blockade 6
    • Carvedilol leads to a significantly greater decrease in hepatic venous pressure gradient than propranolol 6
    • Can be used in patients who don't respond to propranolol 6

Secondary Prevention (After First Bleed)

• Combination of NSBBs and endoscopic treatment (variceal band ligation) is recommended 2, 5
• NSBBs alone may be less successful for secondary prophylaxis compared to their use in primary prevention 5

Mechanism of Action

• NSBBs reduce portal pressure through two mechanisms 2, 7:
  • Decreasing cardiac output via β1-receptor blockade
  • Producing splanchnic vasoconstriction via β2-receptor inhibition, reducing portal venous inflow
• The goal is to decrease hepatic venous pressure gradient by ≥20% from baseline or to <12 mmHg 2, 7
• NSBBs reduce the risk of first variceal bleeding from 30% to 14% in patients with medium/large varices 2

Special Considerations

• In acute bleeding, beta-blockers should be temporarily suspended if the patient is hypotensive (systolic BP <90 mmHg) 1
• Contraindications to NSBBs include hypotension, bradycardia, and severe reactive airway disease 2, 7
• A short course of prophylactic antibiotics is recommended in patients with bleeding varices 1
• Isosorbide mononitrate is not recommended as monotherapy due to systemic hypotensive effects but may be combined with beta-blockers in non-responders 2, 8

Monitoring

• Patients on NSBBs should have target heart rate (55-60 bpm) and systolic blood pressure monitored 2
• The desired reduction of 20% in portal pressure gradient is achieved in about 50-75% of patients with propranolol or carvedilol 1, 7