Terlipressin, a provasopressin drug exhibits direct vasoconstrictor properties: Consequences on heart perfusion and performance*

Abstract

Besides long lasting effect through slow conversion into LVP, terlipressin is a fast acting vasopressor peptide per se that has an impact on coronary circulation and myocardial function.

Short-term effects of terlipressin bolus infusion on sublingual microcirculatory blood flow during septic shock

“…In this regard, it is particularly important that terlipressin is a prodrug capable of releasing sustained amounts of the active metabolite lysine-vasopressin, and therefore providing a prolonged biological effect. In addition, Ryckwaert et al [12] have recently demonstrated that terlipressin itself has intrinsic vasoconstrictive effects. Therefore, terlipressin may be considered as a fast-acting vasopressor peptide itself, exerting long-lasting drug effects through the slow release of lysine-vasopressin.…”

“…1-2 mg), microvessels may reach a near maximal vasoconstriction in the very early phase after terlipressin administration [8,12], whereas 6 h later, 0.5 mg of terlipressin may exert significant vasoconstrictive effects without compromising the microcirculation. This strengthens the concept that a continuous infusion of terlipressin may be as effective as bolus injection in restoring systemic blood pressure, and avoids the risk of early uncontrolled vasoconstriction [13,14].…”

Vasopressin and Its Immune Effects in Septic Shock

“…Furthermore, vasopressin may increase coronary arterial vasoconstriction and therefore has the potential to decrease coronary blood flow and induce ischemia. Indeed, the more selective V1 receptor agonist, terlipressin, induced coronary vasoconstriction in an animal model which was associated with a decrease in contractile function [44] . In another animal model of cardiac ischemia, vasopressin infusion resulted in decreased vital organ blood flow, in particular to the heart [45] .…”

Treatment and management of ascites and hepatorenal syndrome: an update

“…Therefore, patients with coronary heart disease, peripheral vascular disease, and/or cerebrovascular disease should not be treated with terlipressin. Some of these complications may be caused by the bolus injection, because of the acute effect of the prodrug [Ryckwaert et al 2009]. A continuous infusion may overcome this problem [Angeli et al 2009].…”

“…Because ornipressin was removed from the market, subsequent studies were performed using terlipressin. Terlipressin is a triglycyl-lysine-vasopressin with a vasoconstrictive effect per se when given as a bolus and an additional long-acting vasoconstrictive effect caused by lysine-vasopressin, which is produced by triglycyl-lysine-vasopressin degradation [Ryckwaert et al 2009]. Vasopressors such as terlipressin induce vasoconstriction in the splanchnic vasculature by acting on vasopressin 1 receptors, resulting in redistribution of blood flow to the kidneys.…”