Vasopressin Analogues

VASOPRESSIN ANALOGUES

Lypressin

It is 8-lysine vasopressin. Though somewhat less potent than AVP, it acts on both V₁ and V₂ receptors and has longer duration of action (4–6 hours). It is being used in place of AVP—mostly for V₁ receptor mediated actions.

PETRESIN, VASOPIN 20 IU/ml inj; 10 IU i.m. or s.c. or 20 IU diluted in 100–200 ml of dextrose solution and infused i.v. over 10–20 min.

Terlipressin

This synthetic prodrug of vasopressin is specifically used for bleeding esophageal varices; may produce less severe adverse effects than lypressin.

Dose: 2 mg i.v., repeat 1–2 mg every 4–6 hours as needed. GLYPRESSIN 1 mg freeze dried powder with 5 ml diluent for inj.

Desmopressin (dDAVP)

This synthetic peptide is a selective V₂ agonist; 12 times more potent antidiuretic than AVP, but has negligible vasoconstrictor activity. It is also longer acting because enzymatic degradation is slow; t½ 1–2 hours; duration of action 8–12 hours. Desmopressin is the preparation of choice for all V₂ receptor related indications. The intranasal route is preferred, though bioavailability is only 10–20%. An oral formulation has been recently marketed with a bioavailability of 1–2%; oral dose is 10–15 times higher than intranasal dose, but systemic effects are produced and nasal side effects are avoided. Most patients find oral tablet more convenient.

Dose: Intranasal: Adults 10–40 μg/day in 2–3 divided doses, children 5–10 μg at bed time.

Oral: 0.1–0.2 mg TDS.

Parenteral (s.c. or i.v.) 2–4 μg/day in 2–3 divided doses. MINIRIN 100 μg/ml nasal spray (10 μg per actuation); 100 μg/ml intranasal solution in 2.5 ml bottle with applicator; 0.1 mg tablets; 4 μg/ml inj.

Uses

A) Based on V₂ Actions (Desmopressin is the drug of choice)

1. Diabetes Insipidus

DI of pituitary origin (neurogenic) is the most important indication for vasopressin. It is ineffective in renal (nephrogenic) DI, since kidney is unresponsive to ADH. Lifelong therapy is required, except in some cases of head injury or neurosurgery, where DI occurs transiently.

The dose of desmopressin is individualized by measuring 24 hour urine volume. Aqueous vasopressin or lypressin injection is impracticable for long-term treatment. It can be used in transient DI and to differentiate neurogenic from nephrogenic DI—urine volume is reduced and its osmolarity increased if DI is due to deficiency of ADH, but not when it is due to unresponsiveness of kidney to ADH. Desmopressin 2 μg i.m. is the preparation of choice now for the same purpose.

2) Bedwetting In Children And Nocturia In Adults

Intranasal or oral desmopressin at bedtime controls primary nocturia by reducing urine volume. Nocturnal voids are reduced to nearly half and first sleep period in adults is increased by ~2 hr. Fluid intake must be restricted 1 hr before and till 8 hr after the dose to avoid fluid retention. Monitor BP and body weight periodically to check fluid overload. Withdraw for one week every 3 months for reassessment.

3. Renal Concentration Test

5–10 U i.m. of aqueous vasopressin or 2 μg of desmopressin causes maximum urinary concentration.

4. Haemophilia, Von Willebrand’s Disease

AVP may check bleeding by releasing coagulation factor VIII and von Willebrand’s factor. Desmopressin is the preferred preparation in a dose of 0.3 μg/kg diluted in 50 ml saline and infused i.v. over 30 min.

B) Based on V₁ Actions

1. Bleeding Esophageal Varices

Vasopressin/ terlipressin often stop bleeding by constricting mesenteric blood vessels and reducing blood flow through the liver to the varices, allowing clot formation. Terlipressin stops bleeding in ~80% and has been shown to improve survival. It has replaced AVP because of fewer adverse effects and greater convenience in use. Octreotide (a somatostatin analogue) injected i.v. is an alternative. However, definitive therapy of varices remains endoscopic obliteration by sclerotherapy.

2. Before Abdominal Radiography

AVP/lypressin has been occasionally used to drive out gases from bowel.

Adverse Effects

Because of V₂ selectivity desmopressin produces fewer adverse effects than vasopressin, lypressin or terlipressin. However, transient headache and flushing are frequent.

Nasal irritation, congestion, rhinitis, ulceration and epistaxis can occur on local application. Systemic side effects are: belching, nausea, abdominal cramps, pallor, urge to defecate, backache in females (due to uterine contraction). Fluid retention and hyponatraemia may develop.

AVP can cause bradycardia, increase cardiac afterload and precipitate angina by constricting coronary vessels. It is contraindicated in patients with ischaemic heart disease, hypertension, chronic nephritis and psychogenic polydipsia. Urticaria and other allergies are possible with any preparation.