Pharm - Vasopressin

Question 1

What is vasopressin and what are its physiological functions?

Answer 1

Vasopressin is a hormone synthesised in the hypothalamus and released from the posterior pituitary. It has a significant role in regulating plasma volume and osmolality.It has additional activity as a neurotransmitter in the brain regulating circadian rhythm, thermoregulation and ACTH release.Vasopressin acts on V1, V2, V3 and oxytocin-type receptors.V1 receptors: - activation of V1 receptors on vascular smooth muscle in systemic, splanchnic, renal and coronary beds leads to activation of phospholipase C via GPCR and increased intracellular calcium leading to vasocontriction. - activation of V1 receptors in pulmonary circulation leads to vasodilation by nitric oxide release.V2 receptors: - located in DCT and collecting duct of kidney - via GPCR leads to activation of adenylate cyclase, increasing cAMP and mobilisation of aquaporin channels to the apical membrane of tubules. - on endothelial cells activation causes release of vWF and factor VIIIV3 receptors: - central nervous system thought to mediate ACTH release and thermoregulation.

Question 2

What uses does vasopressin have in Critical Care?

Answer 2

1. Vasoconstriction in septic shock (VASST trial showed non-inferiority to NA).
2. Management of diabetes insipidus
3. Management of bleeding abnormalities - vWF deficiency and Haemophilia A (factor VIII deficiency)
4. Management of oesophageal variceal bleeding

Question 3

What can you tell me about diabetes insipidus?

Answer 3

Can be divided into cranial and nephrogenic:
Cranial (deficiency of vasopressin release from posterior pituitary):
- Familial
- Iatrogenic (Neurosurgery)
- Tumours
- Infection
- Sarcoidosis
- Vascular (haemorrhage, stroke)
- Trauma

-Nephrogenic:
- Familial
- Renal tubular acidosis
- Drugs e.g. lithium, demeclocyclineIt is treated by removing the underlying cause.

Desmopressin/DDAVP can reduce the polyuria and polydypsia.

Question 4

What are the causes of SIADH?

Answer 4

1. Ectopic secretion:- tumours: small cell lung cancer
2. central nervous system disorders:- infarction, tumours, infection, trauma
3. Pulmonary infection
4. Drugs (e.g. carbamazepine)

Question 5

What is SIADH?

Answer 5

Syndrome of inappropriate anti-diuretic hormone.Usually suggesting inappropriate over production.Resulting in free water reabsorption from DCT and collecting ducts causing hypo-osmolar, euvolaemic hyponatraemia in the absence diuretic therapy.