From the Guidelines
The main mechanism responsible for reversal of hepatorenal syndrome by terlipressin is peripheral-vasal constriction (option 4). Terlipressin is a vasopressin analog that acts primarily on V1 receptors in the splanchnic circulation, causing vasoconstriction of the dilated splanchnic vessels. In hepatorenal syndrome, there is pathological splanchnic vasodilation which leads to decreased effective arterial blood volume, activation of vasoconstrictor systems, and subsequent renal vasoconstriction with reduced renal blood flow. By constricting the peripheral splanchnic vessels, terlipressin helps redistribute blood from the splanchnic circulation back to the systemic circulation, increasing effective arterial blood volume and mean arterial pressure. This leads to improved renal perfusion, decreased activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, and ultimately improved renal function. Terlipressin is typically administered at 1-2 mg every 4-6 hours intravenously for up to 14 days in the treatment of hepatorenal syndrome, often in combination with albumin infusion to further improve intravascular volume, as supported by recent studies 1. Predictors of response to terlipressin treatment include markers of better liver function, such as a bilirubin of ≤ 10 mg/dL, better kidney function by an sCr of ≤ 5 mg/dL, an increase in the MAP of ≥ 5 mm Hg with treatment, and lower grades of acute-on-chronic liver failure (ACLF) 1. It is essential to monitor patients on terlipressin for the development of ischemic complications, such as arrhythmia, angina, and splanchnic and digital ischemia, and to exercise caution when administering terlipressin to patients with known cardiac failure or underlying respiratory conditions 1. The use of a continuous infusion of terlipressin has been shown to achieve the same efficacy as bolus dosing with a lower total daily dose and fewer side effects 1. Overall, the evidence supports the use of terlipressin as a effective treatment for hepatorenal syndrome, with peripheral-vasal constriction being the main mechanism responsible for its therapeutic effect.
From the FDA Drug Label
Terlipressin is a synthetic vasopressin analogue with twice the selectivity for vasopressin V1 receptors versus V2 receptors. Terlipressin acts as both a prodrug for lysine-vasopressin, as well as having pharmacologic activity on its own Terlipressin is thought to increase renal blood flow in patients with hepatorenal syndrome by reducing portal hypertension and blood circulation in portal vessels and increasing effective arterial volume and mean arterial pressure (MAP).
The main mechanism responsible for reversal of hepatorenal syndrome by terlipressin is activation of vasopressin receptors, specifically V1 receptors, which leads to vasoconstriction. This is most closely related to option 3. Activation of alpha-adrenergic receptors of the arteriole and venous vascular, although the label specifically mentions vasopressin receptors, not alpha-adrenergic receptors. However, the key concept of vasoconstriction is relevant. 2