Vasopressin Analogues

Chemical

Vasopressin

Synthetic peptide hormone

Terlipressin

Synthetic vasopressin analogue (Most selective for V1 receptor)

Desmopressin

Synthetic vasopressin analogue (V2 selective)

Use

Vasopressin

  1. Cranial DI (ineffective for Renal DI)
  2. Platelet dysfunction (F VIII & vWF deficiency)
  3. Oesophageal variceal haemorrhage
  4. NA sparing in Septic Shock

Terlipressin

  1. Acute variceal bleeding
  2. Hepatorenal syndrome

Desmopressin

  1. Mx haemophilia & vWF deficiency
  2. Bleeding post cardiac sx
  3. Antidiuretic (DI of any cause)
  4. Nocturnal enuresis

Dose

Vasopressin

0.01 – 0.1 units/min

Terlipressin

1 – 2mg QID

Desmopressin

IV 2 – 4mcg BD

IN 10 – 40mcg in 24hr

PO 500mcg BD

Presentation

Vasopressin

Clear colourless vial

20U/mL

Terlipressin

Powder. Most be mixed

Desmopressin

Route

Vasopressin

IV

Terlipressin

IV

Desmopressin

PO/IV/Nasally

Onset

Vasopressin

Fast

Terlipressin

Delayed

Desmopressin

Offset

Vasopressin

~30mins

Terlipressin

6hrs

Desmopressin

8 – 12hrs

MoA

Vasopressin

Vasopressin receptor agonist (all GPCR)

  • V1 – vascular smooth m.
  • Gq – intense VC
  • V2 – BASOLATERAL MEMBRANE of distal tubules & collecting duct → ↑H2O reabsorption
  • V2 – endothelial cells → ↑vWF release

Terlipressin

The most selective V1 receptor agonist

  • Gq – intense VC
  • Especially selective for splanchnic circulation

Desmopressin

Selective V2 receptor agonist

  • G5 – basolateral membrane of tubule cell → ↑Aquaporin 2 insertion – ↑H2O reabsorption
  • G5 – endothelial cells → ↑vWF release
  • Promotes platelet adhesion
  • Protects F VIII from breakdown in plasma

PD

CVS

Vasopressin

  • ↑SVR
  • ↑Circulating vol
  • ↑CO
  • CA vc & ↑afterload = ↓Myocardial O2­ delivery

Terlipressin

Desmopressin

GI

Vasopressin

  • Marked splanchnic VC
  • ↑Glycogenolysis

Terlipressin

↓↓↓ portal pressure

Desmopressin

Renal

Vasopressin

↑H2O reabsorption

Terlipressin

Desmopressin

↑water reabsorption

HAEM

Vasopressin

  • ↑platelet aggregation
  • ↑vWF, ↑F VIII

Terlipressin

Desmopressin

  • ↑Platelet aggregation
  • ↑vWF, ↑F VIII

Side Effects

Side Effects​

Vasopressin

  • Hyponatraemia
  • Hypertensive crisis

Terlipressin

  • Abdominal pain
  • Colic
  • HTN
  • Headache

Desmopressin

  • ↓Na+
  • Headache
  • Insomnia

Contraindication

Vasopressin

  1. H2O retention
  2. IHD
  3. Cerebral vasospasm
  4. Pregnancy → oxytocin like effect → premature uterine contractions

Terlipressin

Desmopressin

PK

A

Vasopressin

0% OBA

Terlipressin

IV only

Desmopressin

0.1% OBA

D

Vasopressin

30% PPB. VD 0.2L/kg

Terlipressin

PPB 30%

Desmopressin

0.3L/kg

M

Vasopressin

  • 65% unchanged by kidneys
  • 35% liver + kidney peptidases

Terlipressin

  • Endothelial peptidases
  • 65% unchanged in urine
  • 35% endothelial peptidases

Desmopressin

  • No liver metabolism

E

Vasopressin

  • Renally
  • t½ B 30 mins  

Terlipressin

  • 65% unchanged in urine

Desmopressin

  • 65% unchanged in kidneys