Terlipressin

Warning

H332 (100%): Harmful if inhaled [Warning Acute toxicity, inhalation]

P261, P271, P304+P340, and P317 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

H01BA04

H - Systemic hormonal preparations, excl. sex hormones and insulins

QH - Systemic hormonal preparations, excl. sex hormones and insulin

Terlipressin mimics the biological effects of endogenous vasopressin, but it displays increased selectivity for the V1 receptor and a longer half-life than vasopressin. These pharmacokinetic and molecular properties of terlipressin give it several advantages, such as the prevention of rebound hypotension when the drug is stopped and convenience in patients with limited intravenous access. Terlipressin increases arterial pressure (diastolic, systolic, and mean) and decreases heart rate in patients with hepatorenal syndrome type 1 (HRS-1). After the administration of a single 0.85 mg dose of terlipressin in patients with HRS-1, cardiovascular effects were observed within five minutes after dosing and were maintained for at least six hours after dosing. The maximum change in blood pressure and heart rate occurred at 1.2 to two hours post-dose.

Endogenous vasopressin, also referred to as antidiuretic hormone (ADH) or arginine vasopressin (AVP), regulates important physiological processes such as osmotic balance, blood pressure regulation, sodium homeostasis, and kidney functioning. It is a nonapeptide synthesized in the hypothalamus and stored in the posterior pituitary. Vasopressin mediates its biological effects by binding to three subtypes of vasopressin receptors. V1 receptors are expressed on vascular smooth muscle and many other cells such as hepatocytes: activating these G-protein-coupled receptors leads to vasoconstriction. V2 receptors are predominantly expressed on the basolateral membrane of the distal tubule and collecting ducts of the kidney: these receptors are responsible for the antidiuretic effect of vasopressin, regulating water permeability of kidney tubules and therefore maintaining water homeostasis. V3 receptors mediate the effects of vasopressin on the central nervous system. Vasopressin is considered a stress hormone as it is released into the bloodstream in response to various volume and pressure stimuli, such as pain, surgery, syncope and shock. Shock conditions such as hypovolemia initially cause an increase in the release of vasopressin to maintain organ perfusion; however, as the shock state progresses, plasma vasopressin concentrations decrease due to several causes such as depleted stores of vasopressin in refractory shock and a central inhibitory effect of initially elevated vasopressin levels on further vasopressin release. Terlipressin is a synthetic vasopressin analogue that can cause sustained increases in blood pressure in patients with shock conditions. It exhibits twice the selectivity for vasopressin V1 receptors versus V2 receptors. Terlipressin is pharmacologically active but acts as a prodrug for [lypressin] (also known as lysine vasopressin), a vasoconstrictor and antidiuretic agent. The exact mechanism of action of terlipressin is not fully understood; however, terlipressin works to cause vasoconstriction in shock and other conditions associated with vasodilation. Hepatorenal syndrome (HRS) is caused by splanchnic and systemic arterial vasodilation along with a reduced mean arterial pressure (MAP) and cardiac output, resulting in a marked decrease in effective circulating volume. Terlipressin is thought to increase renal blood flow in patients with HRS-1 by reducing portal hypertension and blood circulation in portal vessels and increasing effective arterial volume and mean arterial pressure (MAP).