ADH Flashcards
ADH synthesised by
hypothalamic neurons (supraoptic and paraventricular nucleus)
Action of ADH through
Vasopressin receptors (All GPCR)
V1 / V1A - BV- VC (vasopressin) - increases BP (treatment of shock)
V2 - endothelial cells where it increases synthesis of vWF, Factor 8 clotting factors & kidney where it acts on medulla of collecting duct and increases Aquaporin 2 and reabsorbs water, leading to decreased urine volume (antidiuretic)
V3 / V1B - pituitary, where it increases release of ACTH and endorphins
Vasopressin agonists
Natural
1. Arginine vasopressin - human form - iv
2. Lysine vasopressin - longer acting - from swine(pigs) -iv
Synthetic
1. Terlipressin - V1 agonist - iv
2. Felypressin - V1 agonist - iv
3. Desmopressin (DDAVP) - V2 agonist - oral, nasal spray, inj - longest acting & most potent
Use of natural vasopressin agonists
Treatment of resistant shock (increases BP)
Use of Terlipressin
DOC for bleeding oesophageal varices & DOC for hepatorenal syndrome (cirrhosis -> low albumin-> reduces blood to kidney ->ARF: Tx: Albumin + Terlipressin)
Use of Felypressin
add to local aesthetics to reduce absorption
use of Desmopressin
Tx of haemophilia A (increases factor 8 synthesis), DOC of neurogenic DI, DOC of nocturnal eneurosis
SE of Desmopressin
SE: dilution hyponatremia (nausea/vomiting, seizures, central pontine myelinolysis)
Vasopressin agonists
Natural
1. Arginine vasopressin - human form - iv
2. Lysine vasopressin - longer acting - from swine(pigs) -iv
Treatment of resistant shock (increases BP)
Synthetic
1. Terlipressin - V1 agonist - iv - DOC for bleeding oesophageal varices & DOC for hepatorenal syndrome (cirrhosis -> low albumin-> reduces blood to kidney ->ARF: Tx: Albumin + Terlipressin)
2. Felypressin - V1 agonist - iv - add to local aesthetics to reduce absorption
3. Desmopressin (DDAVP) - V2 agonist - oral, nasal spray, inj - longest acting & most potent - Tx of haemophilia A (increases factor 8 synthesis), DOC of neurogenic DI, DOC of nocturnal eneurosis
SE: dilution hyponatremia (nausea/vomiting, seizures, central pontine myelinolysis)
Nocturnal enuresis/bedwetting
Treatment if child> 6 yrs
1st: Training - reduce water intake before sleep & alarm method
2nd -
Desmopressin (DOC) - oral, nasal spray - reduces renal volume
Oxybutinin - oral - anticholinergic drug - relax detrusor muscle of bladder
Imipramine - oral - TCA - has anticholinergic properties
Neurogenic DI
defect in ADH hormone
1. no ADH secretion - neurogenic/ central DI - DOC: Desmopressin
Other drugs - Carbamazepine (AED), Chlorpropamide (DM) : increases ADH secretion from brain
Desmopressin challenge test
Desmopressin challenge test - only improvement in neurogenic DI - increase in urine osmolarity, while urine remains dilute in nephrogenic DI
nephrogenic DI
receptors of ADH not responding - nephrogenic DI - DOC: thiazides + Indomethacin (NSAID) - CI: in Li toxicity
Li induced nephrogenic DI - Amiloride
drug in both types of DI
Thiazides can be used in both types of DI
Desmopressin can be used only in neurogenic DI
Diabetes Insipidus
defect in ADH hormone
1. no ADH secretion - neurogenic/ central DI - DOC: Desmopressin
Other drugs - Carbamazepine (AED), Chlorpropamide (DM) : increases ADH secretion from brain
[Desmopressin challenge test - only improvement in neurogenic DI - increase in urine osmolarity, while urine remains dilute in nephrogenic DI]
- receptors of ADH not responding - nephrogenic DI - DOC: thiazides + Indomethacin (NSAID) - CI: in Li toxicity
Li induced nephrogenic DI - Amiloride
Thiazides can be used in both types of DI
Desmopressin can be used only in neurogenic DI
Vasopressin antagonist
Vaptan - block VP receptor
- Conivaptan - V1A + V2 antagonist - iv
- Tolvaptan - V2 antagonist - oral, iv
Mozavaptan, Lixivaptan
Tx of SIADH ( syndrome of inappropriate ADH secretion) -
mc due to head injury, head tumours
adult polycystic kidney disease
CHF
CLD
CKD
- Demeclocycline (antibiotic) - V2 antagonist
Tx of SIADH
Tx of SIADH ( syndrome of inappropriate ADH secretion) -
mc due to head injury, head tumours
adult polycystic kidney disease
CHF
CLD
CKD
New drugs in trials
- Nelivaptan - V3 antagonist
- Relcovaptan, Balovaptan - V1A antagonist
Drugs causing SIADH
dilutional hyponatremia in blood
Carbamazepine
Chlorpropamide
Cyclophosphamide
Vincristine
SSRI
Drugs causing Diabetes Insipidus
dehydration, dilute urine
LAPDog
Lithium - blocks ADH receptors - nephrogenic DI
Alcohol - decrease ADH secretion - neurogenic DI
Phenytoin - decrease ADH secretion - neurogenic DI
Demeclocycline - blocks ADH receptors - nephrogenic DI
why is there excessive urination after drinking alcohol
Alcohol reduces ADH secretion and increases water loss in urine and causes polyuria
