Acts at the GPCR Vasopressin receptors

V1 on vascular smooth muscle
Inc intracellular Ca conc, vasoconstrictive
V1 on platelets
increase platelet aggregation

V2 on the nephron
Aquaporin-2 trafficking from intracellular vesicle membrane – allowing water reabsorption
V2 on endothelial cells – allow vWF release that prevents breakdown of factor VIII

V3 (prev V1b) on pituitary
Contribute to ACTH release

Acts at the GPCR Vasopressin receptors
V1 on vascular smooth muscle – vasoconstrictive – markedly less than ADH (1500x less than ADH)
V1 on platelets - increase platelet aggregation – more potent than ADH
V2 on the nephron - expressed in the renal collecting duct (CD) - antidiuretic actions (10x ADH)

Acts at the GPCR Vasopressin receptors
V1 on vascular smooth muscle - vasoconstrictive
V1 on platelets - increase platelet aggregation
V2 on the nephron - antidiuretic actions

CVS: - in the presence of shock, vasopressin causes an increase in MAP and SVR via its vasoconstrictor effect. - In low doses it causes vasodilation in certain vascular beds in animal models. - It causes pulmonary vasodilation in hypoxic and physiological conditions. GU: a reduction in urine output and polydipsia is seen following administration in DI GIT: Gastric smooth muscle contraction Other: Increase in vWF and Factor 8 can be detected

CVS:
- in the presence of shock, vasopressin causes an increase in MAP and SVR via its vasoconstrictor effect.
- In low doses it causes vasodilation in certain vascular beds in animal models.
- It causes pulmonary vasodilation in hypoxic and physiological conditions.

GU:
a reduction in urine output and polydipsia is seen following administration in DI

GIT:
Gastric smooth muscle contraction

Other: Increase in vWF and Factor 8 can be detected

Vasoconstriction – increased MAP
Pulmonary vasodilation

Increased vWF, factor VIII

Antidiuretic: reduced urine output, resolution of polydypsia

Vasoconstriction (less)
Increased platelet aggregation
Antidiuretic (more)

Vasoconstriction
Increased platelet aggregation
Antidiuretic

IV only

BA
SL: 0.25%
PO: 0.08-0.16%
Intranasal: 10%

IV only

limited data

No PB

20%

30%

0.14 L/kg

0.2-0.32 L/kg

0.5 L/kg
Biphasic plasma curve

Metabolised by peptidases (Vasopressinases) to amino acids

Minimal hepatic metabolism

minimal

65% unchanged in urine

65% unchanged in urine

urine

10-35 mins

2-3hrs

50-70min

Hyponatraemia with H2O retention
May cause severe vasoconstriction -CVC only
Arrhythmias at higher doses
GIT smooth muscle constriction
cramping, nausea, diarrhoea

OD – Hyponatremia (Seizure, altered mental state, arrythmias, edema)

Hyponatraemia with H2O retention
May cause severe vasoconstriction -CVC only
Arrhythmias at higher doses
GIT smooth muscle constriction
cramping, nausea, diarrhoea

Prod hypothal.
released by the posterior pituitary
similar to oxytocin complex molecule wt

Deamino Arginine Vasopressin

Prodrug of lysine Vasopressin

Endogenous vasopressin hormone, clinically used as a non-adrenergic vasopressor.

NON-ADRENERGIC

Vasopressin Hormone

Vasopressin Analogue

Vasopressin Analogue

Catecholamine sparing drug in shock
Diabetes insipidus
Bleeding in vWF def / mild haemophilia

Central DI – ADH replacement (Intranasal/parenteral)
Nocturnal polyuria (intranasal).
Haemostasis in Haemophilia with fVIII def or Type 1 Von Willebrand disease during surgical procedures and postoperatively to maintain hemostasis (parenteral).

Commonly used to stop bleeding of varices in the food pipe (oesophagus).

Hepatorenal syndrome

Is a naturally occurring nonapeptide-9AA. Produced hypothal. released by the posterior pituitary. similar to oxytocin complex molecule wt

Is a naturally occurring nonapeptide-9AA.
Produced hypothal.
released by the posterior pituitary.
similar to oxytocin complex molecule wt

Is a naturally occurring nonapeptide-9AA

Synthetic analogue of 8-arginine vasopressin (ADH)

Antidiuretic peptide drug

displays enhanced antidiuretic potency, fewer pressor effects due to V2-selective actions, and a prolonged half-life and duration of action compared to endogenous ADH

analogue of vasopressin – Prodrug
Peiptidases  Lysine vasopressin

used as a vasoactive drug in the management of hypotension. It has been found to be effective when norepinephrine does not help

Longer duration of action than Vasopressin

Level 1

Level 2

Level 2

Acts at the GPCR Vasopressin receptors

Acts at the GPCR Vasopressin receptors

Acts at the GPCR Vasopressin receptors

Rapid onset

measured in international units
20 IU/ml vial
requiring dilution for eff¬ective delivery.
It cannot be given orally as it is
inactivated by trypsin

sublingual tablet, intra nasal spray, IV/IM

IV

IV infusion
0.01–0.04 units/min

sublingual tablet, intra nasal spray, IV/IM
0.1 to 1.2 mg divided into 2 or 3 doses

IV
1-2mg terlipressin acetate (0.85-1.7mg Terlipressin) Q6 hourly