Description

Terlipressin is a synthetic analogue of the hormone vasopressin. It is a prodrug, meaning it is an inactive substance that is metabolized in the body into its active form, lypressin (also known as lysine vasopressin). It is a potent vasoconstrictor, with a long-lasting and more selective effect than vasopressin. Terlipressin is administered intravenously.

Indications

Terlipressin is used to treat conditions characterized by significant vasodilation, particularly in the splanchnic circulation (the blood supply to the abdominal organs). Its primary indications are:

• Hepatorenal syndrome (HRS): A life-threatening condition in people with severe liver disease where the kidneys suddenly fail. Terlipressin is used to improve kidney function in adults with this condition.
• Bleeding esophageal varices: This is a severe complication of liver disease where enlarged veins in the esophagus rupture and bleed. Terlipressin is used to control this bleeding.

Mechanism of Action

Terlipressin’s mechanism of action is based on its role as a vasopressin receptor agonist. Here is a breakdown of how it works:

1. Prodrug conversion: After administration, terlipressin is slowly converted by enzymes in the body into its active metabolite, lypressin. This gradual conversion contributes to its sustained effect.
2. Vasopressin receptor binding: Lypressin primarily binds to and activates V1 vasopressin receptors, which are found on the smooth muscle of blood vessels. It has a higher selectivity for V1 receptors than V2 receptors.
3. Vasoconstriction: The activation of V1 receptors causes powerful vasoconstriction (narrowing of blood vessels). This effect is most pronounced in the splanchnic circulation, which is abnormally dilated in conditions like hepatorenal syndrome and portal hypertension.
4. Blood flow redistribution: By constricting the splanchnic blood vessels, terlipressin reduces blood flow to the portal venous system. This, in turn, decreases the pressure within the portal vein and esophageal varices, helping to control bleeding.
5. Improved kidney perfusion: In hepatorenal syndrome, the widespread vasodilation in the splanchnic circulation leads to a decrease in the effective arterial blood volume, which triggers a compensatory constriction of blood vessels to the kidneys. By reversing the splanchnic vasodilation, terlipressin increases mean arterial pressure and redistributes blood flow, improving perfusion to the kidneys and restoring their function.