Glypressin Mechanism of Action

Pharmacotherapeutic group: Posterior pituitary lobe hormones (vasopressin and analogues). ATC code: H01B A04.
Pharmacology: Pharmacodynamics: Terlipressin (Triglycyl-Lysine-Vasopressin) is a synthetic analogue of the natural posterior pituitary hormone vasopressin. Terlipressin is a pro-drug with partial, intrinsic activity by itself. Terlipressin is transformed into the fully active metabolite lysine-vasopressin (LVP) by enzymatic cleavage. LVP remains within the therapeutic concentration range over a period of 4-6 hours.
Doses of 1 and 2 mg terlipressin acetate effectively reduce the portal venous pressure and produce marked vasoconstriction. The lowering of portal pressure and azygos blood flow is dependent on dose. The effect of the low dose is reduced after 3 hours, while haemodynamic data show that 2 mg terlipressin acetate is more effective than 1 mg terlipressin acetate with a sustained effect throughout the treatment period (4 to 6 hours).
Clinical efficacy and safety: Continuous IV infusion versus IV boluses in the treatment of type 1 hepatorenal syndrome in patients with cirrhosis.
The safety of continuous IV infusion of terlipressin has been compared with IV bolus in an open-label randomised controlled multicentre trial. Seventy-eight patients with type 1 hepatorenal syndrome were randomly assigned to either continuous IV infusion of terlipressin acetate at the initial dose of 2 mg/day or IV boluses of terlipressin at the initial dose of 0.5 mg every 4 hours. In case of no response, the dose was progressively increased to a final dose of 12 mg/day in both groups. Albumin was given at the same dose in both groups. The primary endpoint was defined as the prevalence of treatment-related adverse events (AEs) between the two groups. Both the total rate of treatment-related AEs as well as severe treatment-related AEs were lower in the continuous infusion group than in the bolus group (all treatment-related AEs: 12/34 patients (35%) vs 23/37 patients (62%), p<0.025. Severe treatment-related AEs: 7/34 patients (21%) vs 16/37 patients (43%); p<0.05). The rate of response to terlipressin was not statistically significantly different between the continuous infusion and bolus groups (76% vs 65%). The probability of 90-day transplant-free survival was not significantly different between the continuous infusion group and the bolus group (53% vs 69%).
Pharmacokinetics: GLYPRESSIN is administered by bolus i.v. injection. It shows a biphasic plasma level curve which indicates that a two compartment model can be applied. The half-life of distribution (T½_α) is about 8-10 minutes. The half-life of elimination (T½_β) is about 50-70 minutes.
Lysine vasopressin reaches maximum plasma levels about 1-2 hours following i.v. administration and has a duration of activity of 4-6 hours.
Toxicology: Preclinical Safety Data: There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections.