1) Antidiuretic hormone (ADH), also known as vasopressin, is formed in the hypothalamus and stored in the pituitary gland. The two main stimuli for ADH release are increases in plasma osmolarity and decreases in extracellular fluid volume.
2) ADH binds to two types of G protein-coupled receptors: V1 receptors that constrict blood vessels and V2 receptors in the kidney's collecting duct that increase water permeability and reduce urine volume.
3) Drugs that decrease urine volume by decreasing water elimination include ADH analogues such as desmopressin, and natriuretics like thiazides and amiloride.
1. Antidiuretics-
Antidiuretic hormone- formed in hypothalamus and stores in pituitary
The two main physiological stimuli for ADH release are rise in plasma osmolarity and contraction
of e.c.f volume.
ADH receptors- G protein coupled receptors; two types;
1) V1- further subtypes -V1a receptors - vascular smooth muscles, uterine and visceral smooth
muscles, platelets, liver, etc.
-The V1b receptors - anterior pituitary, certain areas in brain and in pancreas.
Drugs which decrease urine volume by decreasing water
elimination
Classification
1. ADH and its analogues- Desmopressin, Lypressin, Terlipressin
2. natriuretics – thiazide, Amiloride
3. Miscellaneous- Carbamazepine, Chloropropamide, Indomethacin
2. 2) V2 receptors- primarily on the collecting duct (CD) principal cells and increase their
water permeability through cAMP production.
also present on AscLH cells which activate Na+ K+ 2Cl¯ cotransporter.
Vasodilatory V2 receptors are present on endothelium of blood vessels.
•ACTIONS:
1) Kidney- AVP acts on principal cells in the CD to increase their water permeability.
2) Blood vessels- AVP constricts BV through V1 receptors and increases peripheral resistance.
P/K- inactive orally(destroyed by trypsin), administered parenterally and by intranasal route
• half life time is short ~25min
• action of aqueous vasopressin lasts 3-4hrs.
Vasopressin analogues:
1) Desmopressin- selective V2 agonist, more potent that ADH
2) Terlipressin- prodrug to ADH, used for bleeding esophagitis
Doc in nocturnal enuresis.
3. Uses
1) based on V2 actions
- Diabetes insipidus
- bedwetting in children and nocturia in adults. (DOC- Desmopressin)
- bleeding disorders haemophilia , von willebrand disease etc.
2)Based on V1 actions
- Bleeding oesophageal varices.
-before abdominal radiography.
Adverse effects:
-transient headache and flushing are frequent.
-Nasal irritation, congestion, rhinitis, ulceration and epistaxis can occur on local application.
Systemic side effects are: belching, nausea, abdominal cramps, pallor, urge to defecate.
4. Natriuretics and Miscellaneous
1) Thiazides:
-Diuretic thiazides paradoxically exert an antidiuretic effect in DI.
Thiazides reduce urine volume in both pituitary origin as well as renal DI.
It decreases glomerular filtration of water.
2) Amiloride- drug of choice for lithium induced nephrogenic DI, because
it blocks Li+ entry along with Na+.
3) Chloropromide- reduce urine volume in DI of pituitary origin but not in renal DI. It
sensitizes the kidney to ADH action; thus its efficacy depends on small amounts of the
circulating hormone; it is not active when ADH is totally absent.
4) Carbamazepine- It is an antiepileptic, which reduces urine volume in DI of
pituitary origin.