Glypressin

• Acute Esophageal Variceal Bleeding: To control bleeding in patients with portal hypertension related to liver cirrhosis.
• Hepatorenal Syndrome (Type 1): Used in combination with albumin to improve renal function in patients with hepatorenal syndrome associated with advanced liver disease.
• Off-label/Clinically Accepted Uses:
• Management of shock states refractory to fluid resuscitation, especially in septic or vasodilatory shock.
• Control of other types of gastrointestinal bleeding from portal hypertension.

• Route: Intravenous (IV) bolus injection or slow IV infusion.
• Adults:
• Esophageal Variceal Bleeding: Initial dose 1 mg IV every 4 to 6 hours; may increase to 2 mg every 4 to 6 hours if bleeding persists, maximum 12 mg/day.
• Hepatorenal Syndrome: 1 mg IV every 4 to 6 hours; dose may be adjusted based on response, typically continued for 3 to 14 days.
• Pediatrics: Safety and efficacy not well established; use only if benefits outweigh risks with specialist guidance.
• Elderly: No specific dosage adjustment; monitor closely due to cardiovascular risks.
• Renal/Hepatic Impairment: Use cautiously in severe hepatic impairment (common in target population); monitor closely.
• Administration Notes:
• Administer via slow IV injection or infusion to minimize adverse effects.
• Monitor blood pressure and cardiac status during administration.

Terlipressin is a synthetic analogue of vasopressin with prolonged duration of action. It acts as a vasoconstrictor by binding selectively to vasopressin V1 receptors on vascular smooth muscle, leading to vasoconstriction mainly in the splanchnic circulation. This reduces portal venous pressure and blood flow, thereby controlling variceal bleeding and improving renal perfusion in hepatorenal syndrome through increased effective arterial blood volume.

• Absorption: Given intravenously; bioavailability is 100%.
• Distribution: Widely distributed; plasma protein binding ~30%.
• Metabolism: Terlipressin is a prodrug converted enzymatically to active lysine vasopressin.
• Half-Life: Approximately 6 hours (prolonged effect due to slow conversion).
• Excretion: Mainly metabolized by liver and kidneys; metabolites excreted in urine.

• Pregnancy: Category C — Animal studies have shown adverse effects on fetus at high doses; no well-controlled human studies. Use only if benefits justify risks.
• Lactation: Unknown if excreted in human milk; caution advised.

• Primary Class: Vasopressor and vasoconstrictor agent
• Subclass: Vasopressin analogue

• Known hypersensitivity to terlipressin or vasopressin analogues
• Ischemic heart disease or significant peripheral vascular disease (due to vasoconstriction risk)
• Hyponatremia (relative contraindication)
• Pregnant women unless benefit outweighs risk

• Cardiovascular Risks: May cause hypertension, arrhythmias, myocardial ischemia, or infarction. Monitor ECG and blood pressure closely.
• Ischemic Events: Risk of ischemia in extremities, mesenteric organs, and brain; discontinue if signs appear.
• Hyponatremia: Monitor serum sodium during therapy.
• Renal Impairment: Dose adjustments not well established; careful monitoring required.
• Overdose: Can cause severe vasoconstriction and ischemic complications; treat symptomatically.

Common:

• Abdominal cramps and pain
• Headache
• Bradycardia or palpitations
• Nausea and vomiting

Serious but Rare:

• Myocardial ischemia or infarction
• Ischemic skin necrosis
• Hypertension
• Arrhythmias
• Hyponatremia

Timing: Usually occurs during or shortly after administration; dose-dependent.

• Vasoconstrictors: Additive effects may increase risk of ischemia.
• Beta-blockers and Calcium Channel Blockers: May blunt cardiovascular responses; monitor closely.
• Alcohol: May exacerbate hypotension or vasoconstriction effects.
• No significant CYP450 involvement.

• Recent guidelines continue to recommend terlipressin as first-line vasoconstrictor for esophageal variceal bleeding and hepatorenal syndrome.
• Some countries have approved it specifically for hepatorenal syndrome type 1 treatment.
• Emphasis on cardiovascular monitoring and limiting duration of therapy.

• Store at 2°C to 8°C (refrigerated).
• Protect from light.
• Do not freeze.
• Use reconstituted solution promptly or as per manufacturer instructions.