Vasopressin Analogues

Vasopressin analogues include desmopressin (selective V2 agonist), vasopressin itself, and terlipressin (mainly V1 agonist). They treat central diabetes insipidus, nocturnal enuresis, bleeding disorders, vasodilatory shock, variceal bleeding and hepatorenal syndrome.

Mechanism. V2 receptor activation in the collecting duct inserts aquaporin 2 water channels, concentrating urine, and raises factor VIII and von Willebrand factor. V1 receptor activation on vascular smooth muscle causes vasoconstriction, notably in the splanchnic bed.

Pharmacokinetics. Desmopressin half-life is 2 to 3 hours with duration 6 to 20 hours, dose dependent. Terlipressin is a prodrug converted to lysine vasopressin, with effect lasting 4 to 6 hours. Vasopressin has a half-life of 10 to 20 minutes.

Desmopressin. Intranasal 10 to 40 micrograms daily in 1 to 3 doses; oral 100 to 200 micrograms two to three times daily (total up to 1.2 mg daily); sublingual 60 to 120 micrograms two to three times daily; intravenous or subcutaneous 1 to 4 micrograms daily in 1 or 2 doses.

Terlipressin. Variceal bleeding 2 mg intravenously every 4 hours for 48 hours, then 1 mg every 4 hours for up to 5 days. Hepatorenal syndrome 0.85 to 1 mg every 6 hours or 2 mg over 24 hours as infusion, increased to a maximum of 12 mg daily.

Vasopressin. Septic shock 0.01 to 0.04 units/min as an added vasopressor.

• Central diabetes insipidus: desmopressin at the lowest dose that controls polyuria and thirst, with sodium checks. After pituitary surgery, give by response (a single dose when urine output is high and sodium rising) because of triphasic patterns.
• Nocturnal enuresis (over 5 years): oral 200 to 400 micrograms (melt 120 to 240 micrograms) at bedtime.
• Nocturia in adults: sublingual 25 micrograms (women) or 50 micrograms (men) at bedtime.
• Mild haemophilia A and type 1 von Willebrand disease: 0.3 micrograms/kg intravenously over 20 to 30 minutes (maximum 20 micrograms), repeated every 12 to 24 hours; response fades after 3 to 4 doses.
• Uraemic or drug-induced platelet bleeding: same intravenous dose.
• Hepatorenal syndrome: terlipressin with albumin (20 to 40 g daily); stop if creatinine has not fallen by 25% by day 3 to 4 at the maximum dose.

Special groups. Pregnancy: desmopressin is safe in diabetes insipidus (placental vasopressinase may increase dose needs); avoid terlipressin. Breastfeeding: desmopressin is compatible. Children: enuresis from 5 years; limit fluid from 1 hour before to 8 hours after the dose. Older adults: high hyponatraemia risk, avoid for nocturia over 65 years. Kidney impairment: avoid desmopressin at eGFR under 50 mL/min. Liver impairment: safe. Regional: head injury and pituitary surgery cause temporary diabetes insipidus; intranasal sprays are unstable in heat.

Adverse effects. Desmopressin: hyponatraemia, headache, nausea, fluid overload and seizures. Terlipressin: ischaemia of fingers, bowel and heart, bradycardia, hypertension and respiratory failure with fluid overload. Vasopressin: peripheral and mesenteric ischaemia.

Contraindications. Desmopressin: hyponatraemia, SIADH, heart failure, concurrent loop or thiazide diuretics, polydipsia, and eGFR under 50 mL/min. Terlipressin: hypoxia (oxygen saturation under 90%), volume overload, coronary or peripheral ischaemia, and pregnancy.

Interactions. Carbamazepine, tricyclics, SSRIs and NSAIDs add hyponatraemia with desmopressin. Terlipressin with beta blockers adds bradycardia.

Monitoring. Sodium at 3 and 7 days after starting desmopressin and after dose changes, then every 3 to 6 months; urine output and weight; oxygen saturation and fluid balance with terlipressin.

Referral and escalation. Sodium under 130 mmol/L on desmopressin (stop), hepatorenal syndrome, and variceal bleeding.