What is the effect of Terlipressin (Terlipressin) on disease?

From the Guidelines

Terlipressin is recommended for the treatment of hepatorenal syndrome (HRS) at a dose of 1-2 mg every 4-6 hours by intravenous injection, with the goal of improving renal function and reducing mortality risk. The medication works as a vasopressin analog that causes vasoconstriction in the splanchnic circulation, reducing portal pressure and improving renal perfusion in patients with advanced liver disease 1.

Key Considerations

• Treatment with terlipressin should be initiated as soon as possible, as higher pretreatment serum creatinine is associated with treatment failure 1.
• The dose of terlipressin can be increased to a maximum of 2 mg every 4-6 hours if there is no reduction in serum creatinine at day 3 of therapy by at least 25% compared to the baseline value 1.
• Continuous infusion of terlipressin may be used as an alternative to bolus dosing, with a lower starting dose of 2 mg/d, which may reduce ischemic side effects and increase the dose gradually every 24-48 hours up to a maximum dose of 12 mg/d 1.
• Predictors of response to terlipressin treatment include markers of better liver function, such as a bilirubin of ≤ 10 mg/dL, better kidney function, and an increase in the mean arterial pressure (MAP) of ≥ 5 mm Hg with treatment 1.

Monitoring and Adverse Effects

• Patients on terlipressin need to be monitored for the development of ischemic complications, such as arrhythmia, angina, and splanchnic and digital ischemia 1.
• Treatment should be monitored closely for adverse effects, including abdominal cramps, diarrhea, hyponatremia, and cardiac arrhythmias 1.
• Blood pressure, heart rate, and fluid status should be regularly assessed during administration 1.

Special Considerations

• Terlipressin should not be used in patients with a serum creatinine ≥5 mg/dL, or oxygen saturation of <90% 1.
• Clinicians should exercise caution when ordering terlipressin for patients with known cardiac failure or underlying respiratory conditions, especially those with baseline hypoxemia 1.

From the FDA Drug Label

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). After administration of a single 0. 85 mg dose of terlipressin in patients with hepatorenal syndrome type 1 (HRS-1), an increase in the diastolic, systolic, and mean arterial pressure (MAP), and decrease in heart rate were evident within 5 minutes after dosing and were maintained for at least 6 hours after dosing.

The effect of Terlipressin on disease is to increase renal blood flow in patients with hepatorenal syndrome by:

• Reducing portal hypertension
• Reducing blood circulation in portal vessels
• Increasing effective arterial volume
• Increasing mean arterial pressure (MAP) This is achieved through its mechanism of action as a vasopressin receptor agonist 2, 2, 2.

From the Research

Effects of Terlipressin on Disease

• Terlipressin, a vasopressin agonist, has been shown to have beneficial effects in the treatment of various diseases, including esophageal varices bleeding, hepatorenal syndrome, and septic shock 3, 4, 5.
• In patients with cirrhosis and variceal bleeding, terlipressin reduces portal vein pressure and decreases pressure in esophageal varices, which can be life-saving when skilled endoscopists are not immediately available 3.
• Terlipressin also has a beneficial effect in the treatment of hepatorenal syndrome, with a success rate of up to 75% when combined with volume expansion 3.
• In septic shock patients, terlipressin has been shown to improve organ perfusion and reduce mortality when used in combination with norepinephrine 5.
• The use of terlipressin in critically ill children with liver disease has also been reported, with minimal evidence of gastrointestinal side effects and vasoconstrictive side effects 6.

Mechanism of Action

• Terlipressin exerts its main pharmacological effect through stimulation of vasopressin-1 receptors, which are located in vascular smooth muscle and mediate vasoconstriction 4.
• Terlipressin increases mean arterial pressure and decreases portal flow and pressure within minutes of administration in patients with cirrhosis and portal hypertension 4.
• Terlipressin also improves glomerular filtration and excretion of sodium in patients with ascites 4.

Safety and Efficacy

• The safety profile of terlipressin is favorable, with adverse events mostly being cardiovascular and related to vasoconstriction 4.
• Mortality and withdrawal of terlipressin due to adverse events occur in less than 1% of cases, and mild adverse events related to terlipressin treatment occur in 10%-20% of patients 4.
• The use of terlipressin in combination with albumin has been shown to reverse type 1 hepatorenal syndrome in 33%-60% of cases, and is considered the most efficient therapy for this condition 4.
• Low-dose terlipressin continuous infusion has been shown to improve tissue blood flow, stabilize hemodynamics, and protect organ function in septic shock patients without inducing significant side effects 5, 7.