From the Guidelines
Terlipressin works in hepatorenal syndrome (HRS) by acting as a vasopressin analog that selectively constricts splanchnic blood vessels in the abdomen, thereby improving renal perfusion pressure and glomerular filtration rate 1.
Mechanism of Action
The mechanism of action of terlipressin in HRS involves binding primarily to V1 receptors in the splanchnic vasculature, causing vasoconstriction that redirects blood flow from the splanchnic circulation back to the systemic circulation. This increases effective arterial blood volume and mean arterial pressure, which subsequently improves renal perfusion pressure and glomerular filtration rate.
Key Points
- Terlipressin is a vasopressin analog used to treat HRS by counteracting splanchnic arterial vasodilation and improving renal perfusion 1.
- The typical dosing regimen for terlipressin in HRS is 1-2 mg intravenously every 4-6 hours, with treatment usually continuing for up to 14 days or until serum creatinine decreases to a target level 1.
- Terlipressin should be used alongside albumin infusion (typically 20-40g/day) to optimize intravascular volume 1.
- Treatment response typically occurs within 7-14 days, with approximately 40-50% of patients showing improvement in renal function 1.
- Side effects to monitor include ischemic complications (cardiac, digital, intestinal), arrhythmias, and hyponatremia due to its antidiuretic effects 1.
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 mechanism of action of terlipressin in HRS is through its vasopressin analogue properties, which allow it to:
- Reduce portal hypertension
- Decrease blood circulation in portal vessels
- Increase effective arterial volume
- Increase mean arterial pressure (MAP) This is achieved through its selectivity for vasopressin V1 receptors and its role as a prodrug for lysine-vasopressin 2.
From the Research
Mechanism of Action of Terlipressin in HRS
The mechanism of action of terlipressin in hepatorenal syndrome (HRS) involves:
- Vasoconstriction: Terlipressin is a vasopressin analog that causes vasoconstriction, which increases mean arterial pressure and systemic vascular resistance 3
- Reduction in plasma renin activity: The vasoconstrictor effect of terlipressin reduces plasma renin activity, which is a key factor in the pathogenesis of HRS 3
- Improvement in hemodynamics: Terlipressin improves hemodynamics by increasing glomerular filtration rate and reducing the activity of vasoconstrictor and sodium-conserving hormones 3
- Increased natriuresis: The improvement in hemodynamics with terlipressin is associated with increased natriuresis, which helps to improve renal function 3
Key Effects of Terlipressin in HRS
The key effects of terlipressin in HRS include:
- Reversal of HRS: Terlipressin has been shown to reverse HRS and improve renal function in patients with HRS 4, 3, 5
- Improvement in survival: Terlipressin has been shown to improve survival in patients with HRS, particularly in those who respond to treatment 4, 6
- Bridging to liver transplantation: Terlipressin can be used to bridge patients to liver transplantation, which can improve outcomes in patients with HRS 3
Comparison with Other Treatments
Terlipressin has been compared with other treatments for HRS, including:
- Midodrine and octreotide: Terlipressin has been shown to be more effective than midodrine and octreotide in improving renal function in patients with HRS 4, 7
- Norepinephrine: Terlipressin has been shown to have similar efficacy to norepinephrine in improving renal function in patients with HRS, but with more adverse events 5
- Dopamine: Terlipressin has been shown to have similar efficacy to dopamine in improving renal function in patients with HRS 5