Vasopressin

Chemical

A nonapeptide hormone formed in hypothalamus & released from PPG

  • 1° function is to regulate plasma osmolality & volume, however is also a potent vasoconstrictor

Synthesis

  • In cell bodies of supraoptic & paraventricular nuclei of hypothalamus
  • Transported down axons in neurosecretory granules
  • Stored in nerve terminals of PPG

Release

↑plasma osmolality

  • Detected by osmoreceptors in Ant. Hypothalamus (outside BBB)
  • OsmoR generates electrical impulse → travels axon length → stimulates vasopressin release by PPG

↓ECF volume

  • Hypovolaemia → ↓atrial P → stretch receptors of atria ↓firing rate → afferent fibres of atrial stretch receptors synapse with NTS of medulla → communicates with hypothalamus → controls its release by PPG

AII (by AII receptor on hypothalamus)

Pain

Nausea

Stress

Hypoxaemia

Acidosis

IPPV

Catecholamines → at low levels

  • Activate α1 receptor → stimulates vasopressin release

↓Release

  • ↓plasma osmolality
  • ↑plasma volume

MoA

Vasopressin receptors = all GPCR

  • V1 – vascular smooth m. of systemic, splanchnic, renal, coronary, myometrium & platelets

Gq → activates phospholipid C → ↑IP3 & DAG → ↑intrac Ca2+ → mass VC

  • V1b – adenohypophysis → stimulates release of adrenocorticotropin from APG
  • V2 – distal tubules & collecting duct→BASOLATERAL MEMBRANE

GS → activates AC → ↑cAMP → ↑Ca2+ → AQUAPORIN 2 channels insert on APICAL MEMBRANE → ↑H2O reabsorption

RECALL: Aquaporins insert on Apical membrane → Aquaporins = family of 5 water channels only one is vasopressin sensitive = AqP2

Endothelial cells

GS → induces release of vWF → vWF protects F VIII from break down in plasma → vWF also helps platelets adhere to site of bleeding

  • V3 – pituitary

Gq → activates phospholipase C → ↑IP3 & DAG → ↑intrac Ca2+ → ACTH release → memory & temp regulation

Vasopressin

Chemical

Vasopressin

Synthetic peptide hormone

Terlipressin

Synthetic vasopressin analogue (most sensitive 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)

  1. Oesophageal variceal haemorrhage
  2. NA sparing in septic shock

Terlipressin

  1. Acute variceal bleeding
  2. Hepatorenal sysdrome

Desmopressin

  1. Mx haemphilia & 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: 500 mcg BD

Presentation

Vasopressin

Clear colourless vial 

20U/ml

Terlipressin

Powder. Must be mixed

Desmopressin

Route

Vasopressin

IV

Terlipressin

IV

Desmopressin

PO/IV/Intranasal

Onset/Offset

Vasopressin

Fast – 30mins

Terlipressin

Delayed – 6hrs

Desmopressin

8 – 12hrs

MoA

Vasopressin

Vasopressin receptor agonist (all GPCR)

V1 – vascular smooth m.

Gq → intense VC

 V2 – BASOLATERAL MEMB. Of distal tubules & collecting duct → ↑H2O resorption

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 memb. of tubule cells → ↑aquaporin 2 insertion → ↑H2O reabsorption

G5 → endothelial cells → ↑vWF release → promotes platelet adherence → protects F VIII from

break down in plasma

PD

Vasopressin

CVS

  • ↑SVR
  • ↑circulating volume
  • ↑CO
  • CA VC & ↑afterload = ↓myocardial O2 delivery

GI

  • Marked splanchnic VC
  • ↑glycogenolysis

Renal – ↑H2O reabsorption

Haem

  • ↑platelet aggregation
  • ↑vWF, ↑F VIII

Terlipressin

GI – ↓↓↓portal pressure

Desmopressin

Renal – ↑H2O reabsorption

Haem

  • ↑platelet aggregation
  • ↑vWF, ↑F VIII

Side Effects

Vasopressin

Hyponatraemia

Hypertensive crisis

Terlipressin

Abdo pain

Colic

HTN

Headache

Desmopressin

↓Na+

Headache

Insomnia

Contraindications

Vasopressin

  1. H2O retention
  2. IHD
  3. Cerebral vasospasm
  4. Pregnancy → oxytocin like effect → prem. 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

VD 0.3L/kg

M

Vasopressin

65% unchanged by kidneys

35% liver + kidney peptidases

Terlipressin

Endothelial peptidases

Desmopressin

No liver metabolism

E

Vasopressin

Renally excreted

t ½ B 30 mins

Terlipressin

65% unchanged in urine

35% endothelial peptidases

Desmopressin

65% unchanged in kidneys