Vasopressin Analogues
Chemical
Vasopressin
Synthetic peptide hormone
Terlipressin
Synthetic vasopressin analogue (Most selective for V1 receptor)
Desmopressin
Synthetic vasopressin analogue (V2 selective)
Use
Vasopressin
- Cranial DI (ineffective for Renal DI)
- Platelet dysfunction (F VIII & vWF deficiency)
- Oesophageal variceal haemorrhage
- NA sparing in Septic Shock
Terlipressin
- Acute variceal bleeding
- Hepatorenal syndrome
Desmopressin
- Mx haemophilia & vWF deficiency
- Bleeding post cardiac sx
- Antidiuretic (DI of any cause)
- 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
- H2O retention
- IHD
- Cerebral vasospasm
- 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