Product Name: Terlipressin
Form: Free base
CAS No: 14636-12-5
Molar Mass: 1227.37
Chemical Formula: C52H74N16O15S
Synonyms: 1-Triglycyl-8-lysine Vasopressin, Terlipressinum
Storage: Store at -20℃
Sequence: GGGCYFQNCPKG
Target: Vasopressin V1 receptor
Application:
Terlipressin (CAS: 14636-12-5) is a synthetic analog of vasopressin, also known as antidiuretic hormone (ADH), used primarily in the management of hepatorenal syndrome (HRS) and variceal bleeding. It acts as a prodrug that is metabolized in vivo to form lysine vasopressin, which binds to vasopressin receptors, particularly V1 receptors in vascular smooth muscle cells. Terlipressin induces vasoconstriction of splanchnic vessels, reducing portal hypertension and improving systemic vascular resistance. This mechanism helps to alleviate complications such as renal hypoperfusion in HRS and control bleeding from esophageal varices. In pharmaceutical chemistry, terlipressin's targeted action on vasopressin receptors represents a significant advancement in the management of complications associated with liver cirrhosis, offering a specific and effective therapeutic approach to improve outcomes in patients with HRS and variceal bleeding. Its application underscores its importance in hepatology and critical care medicine, providing life-saving interventions for patients with advanced liver disease. Additionally, ongoing research explores terlipressin's potential in other conditions characterized by vasodilatory shock and renal impairment, highlighting its versatility in cardiovascular and renal therapeutics.
Current Research:
Terlipressin is a synthetic vasopressin analog primarily used in the management of acute variceal bleeding and hepatorenal syndrome (HRS), which are serious complications of cirrhosis. As a prodrug, terlipressin is metabolized into its active form, lysine-vasopressin, which exerts potent vasoconstrictive effects, particularly in the splanchnic circulation. This property is crucial for controlling bleeding from esophageal varices and improving renal perfusion in patients with liver cirrhosis and renal failure. Terlipressin has become an important therapeutic agent in the critical care setting due to its ability to address these life-threatening conditions.
Mechanism of Action
Terlipressin works by mimicking the action of vasopressin (antidiuretic hormone), a naturally occurring peptide hormone that regulates water balance and blood pressure. Upon conversion to its active form, lysine-vasopressin, terlipressin binds to vasopressin receptors (V1 and V2) in the vascular smooth muscle. The primary action occurs through the V1 receptor, which mediates vasoconstriction of the splanchnic vasculature, reducing portal pressure and controlling variceal bleeding. In patients with hepatorenal syndrome, terlipressin also increases renal blood flow, thereby improving kidney function and mitigating the effects of acute renal failure.
Indications and Uses
Terlipressin is indicated for the treatment of acute variceal bleeding and hepatorenal syndrome, both of which are commonly seen in patients with advanced liver cirrhosis. In the case of variceal bleeding, terlipressin helps to control hemorrhage by constricting the blood vessels in the esophageal varices, reducing the blood flow and subsequently the bleeding risk. For patients with hepatorenal syndrome, a condition characterized by kidney dysfunction in the context of cirrhosis, terlipressin helps to improve renal perfusion by vasoconstricting the renal vasculature, thus enhancing kidney function. The drug is typically administered intravenously in a hospital setting, with dosing adjusted based on clinical response.
Efficacy and Clinical Benefits
Clinical studies have demonstrated that terlipressin is highly effective in controlling acute variceal bleeding, significantly reducing mortality rates when used as part of a comprehensive treatment strategy that includes endoscopic interventions and antibiotic therapy. In patients with hepatorenal syndrome, terlipressin has been shown to improve kidney function and increase urine output, often leading to a reversal of renal failure. In addition to its efficacy in these critical situations, terlipressin is well tolerated when administered according to the recommended dosing schedule, with a favorable safety profile compared to other vasoconstrictors. The drug is often used in combination with other therapies to optimize patient outcomes, such as using antibiotics to prevent infections and managing bleeding with endoscopic procedures.
Safety and Tolerability
Terlipressin is generally well tolerated, though it can cause side effects, particularly when used in higher doses or over extended periods. The most common side effects are related to its vasoconstrictive properties and include hypertension, abdominal pain, and ischemic events, particularly in the mesenteric, coronary, or digital circulations. Less common but more serious adverse effects include arrhythmias and myocardial ischemia, especially in patients with preexisting cardiovascular disease. Close monitoring of blood pressure and cardiac function is recommended during therapy. Additionally, terlipressin can cause water retention and hyponatremia, particularly when used in patients with pre-existing fluid imbalances.
Advantages and Limitations
One of the key advantages of terlipressin is its ability to effectively control bleeding in esophageal varices, a complication of cirrhosis that can be fatal if not managed appropriately. In patients with hepatorenal syndrome, terlipressin offers a targeted approach to improving kidney function, which can delay the need for renal replacement therapy (e.g., dialysis). Another advantage is its ability to be administered intravenously, allowing for precise control over dosing in the acute setting. However, its use is limited by potential cardiovascular side effects, particularly in patients with a history of heart disease. Additionally, terlipressin is not suitable for long-term use due to the risk of developing adverse events such as ischemia and hypertension.
Future Directions
Research into terlipressin continues to focus on expanding its therapeutic indications and improving its safety profile. Ongoing clinical trials are investigating its use in other conditions associated with cirrhosis and liver failure, such as spontaneous bacterial peritonitis and acute-on-chronic liver failure. There is also interest in exploring the combination of terlipressin with other pharmacological agents to enhance its effects while minimizing side effects, such as combining it with newer vasodilators or agents that improve endothelial function. Additionally, strategies to develop more targeted and less cardiovascularly risky formulations of vasopressin analogs may further increase the safety and efficacy of terlipressin for a broader range of patients.
Reference:
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