What is the difference in action between terlipressin (Terlipressin) and vasopressin (Vasopressin)?

From the Guidelines

Terlipressin is preferred over vasopressin due to its longer half-life, allowing for intermittent bolus dosing, and its potentially better safety profile regarding ischemic complications, as evidenced by the most recent study 1. The key differences between terlipressin and vasopressin lie in their pharmacokinetics, dosing, and side effect profiles.

Key Differences

• Terlipressin has a longer half-life of 4-6 hours, whereas vasopressin has a half-life of 10-20 minutes, requiring continuous infusion 1.
• Terlipressin is administered as a prodrug, converted to the active form lysine-vasopressin in the body, typically dosed at 1-2 mg IV every 4-6 hours, whereas vasopressin is administered as a continuous IV infusion of 0.2-0.4 units/minute, which can be increased to a maximal dose of 0.8 units/minute 1.
• Terlipressin has greater selectivity for V1 receptors (vascular) over V2 receptors (renal), potentially causing less antidiuretic effect than vasopressin.
• The most recent study 1 recommends terlipressin as the vasoactive drug of choice in the treatment of hepatorenal syndrome and variceal bleeding, due to its safety profile and efficacy.

Clinical Use

• Terlipressin is primarily used for hepatorenal syndrome and variceal bleeding in many countries, while vasopressin is more commonly used for vasodilatory shock, cardiac arrest, and as adjunctive therapy in septic shock.
• The use of terlipressin is recommended over vasopressin in patients with variceal hemorrhage, as it has a better safety profile and is effective in controlling acute variceal hemorrhage, as stated in the study 1.

Safety Profile

• Both medications can cause tissue ischemia, hyponatremia, and cardiac effects, but terlipressin may have a better safety profile regarding ischemic complications.
• The study 1 also notes that terlipressin treatment does not require intensive care unit monitoring and can be administered intravenously through a peripheral line, making it a more convenient option for patients.

From the FDA Drug Label

Terlipressin is a synthetic vasopressin analogue with twice the selectivity for vasopressin V1 receptors versus V2 receptors. The main difference in action between terlipressin and vasopressin is the selectivity for vasopressin receptors. Terlipressin has twice the selectivity for V1 receptors compared to V2 receptors, which may result in different clinical effects.

• V1 receptor selectivity may lead to increased vasoconstriction and blood pressure elevation.
• The exact difference in clinical effects between terlipressin and vasopressin is not explicitly stated in the label, but the difference in receptor selectivity may influence their actions 2.

From the Research

Difference in Action of Terlipressin vs Vasopressin

• Terlipressin is an analog of the natural hormone arginine-vasopressin, used in the treatment of patients with cirrhosis and bleeding esophageal varices (BEV) and in patients with hepatorenal syndrome (HRS) 3.
• Terlipressin exerts its main pharmacological effect through stimulation of vasopressin-1 receptors, which are located in vascular smooth muscle and mediate vasoconstriction 3.
• In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion and it has a safer adverse reactions profile 4.
• Terlipressin decreases failure of initial hemostasis by 34%, decreases mortality by 34%, and is considered a first-line treatment for BEV, when available 3.
• The exact difference in action between terlipressin and vasopressin is not explicitly stated in the provided studies, but it can be inferred that terlipressin has a more targeted effect on vasopressin-1 receptors, resulting in a more selective vasoconstriction 5, 6.
• Terlipressin has been shown to be effective in the treatment of acute variceal hemorrhage, with a 34% relative risk reduction in mortality, and may be considered the vasoactive agent of choice in acute variceal bleeding 4.
• Vasopressin, on the other hand, is a natural hormone that has a broader range of effects, including vasoconstriction, but its use is not as well-studied as terlipressin in the context of BEV and HRS 3, 5.

Mechanism of Action

• Terlipressin reduces portal vein pressure and decreases the pressure in esophageal varices by increasing systemic vascular resistance, particularly in the splanchnic area 5.
• Terlipressin also improves glomerular filtration and excretion of sodium in patients with ascites, and reverses type 1 HRS in 33%-60% of cases when used in combination with albumin 3.
• The mechanism of action of vasopressin is not explicitly stated in the provided studies, but it is known to have a broader range of effects, including vasoconstriction, which may not be as targeted as terlipressin 3, 5.

Clinical Use

• Terlipressin is used in the treatment of patients with cirrhosis and bleeding esophageal varices (BEV) and in patients with hepatorenal syndrome (HRS) 3, 5.
• Terlipressin is also used as an adjunct vasopressor agent in the management of vasodilatory hyperdynamic septic shock 7.
• The clinical use of vasopressin is not as well-studied as terlipressin in the context of BEV and HRS, but it may be used in certain clinical situations where vasoconstriction is desired 3, 5.