2. 1. VASOPRESSSIN
• Antidiuretic hormonev ( ADH) , Arginine
vasopressin ( AVP)
• Nonapeptide
• Posterior pitiutary( source)
Cystein at 1 and 6 position and the disulfide
bond is essential for its Antidiuretic activity.
3. REGULATION OF SECRETION
• STIMULUS:
MAJOR
• Increase in PLASMA OSMOLALITY
MINOR
• Severe hypovolemia/hypotension
• Certain endogenous hormones /
neurotransmitters
• Pharmacologic agents
5. Physiological effects of ADH
1.↑ BP due to vasoconstriction ( V1a)
2.↓ urine output ( water reabsorbtion)
3. ACTH from anterior pitiutary
4. ↓ sweating
6.
7. VASOPRESSINRECEPTOR
CHARACTERISTICS
V 1a V 1b ( V 3) V2
LOCATION Vascular & smooth
muscle, platelets,
hepatatocytes
anterior pitiutary CD cells of kidney,
vascular
endothelium
FUNCTION Vasoconstriction ,
platelet aggregation
, glycogenolysis
ACTH release Antidiuretic action
MECHANISM Release of ca+2 by
PLC / IP3 – DAG
pathway
same as V1a ++ of adenyl
cyclase
12. Contd..
2. Contraction of intestinal
smooth muscle :
Postoperative ileus
Intestinal gas before abdominal radiography
3. Portal HT :
↓ haemorrhage during surgery
4. Acute haemorrhagic gastritis
13. V2 receptor action
1. Diabetes insipidus : 2 types
– CENTRAL DI – deficiency of ADH
– NEPHROGENIC DI –non functional ADH receptor
not responsive to ADH
Symptoms:-
– Polyuria – kidneys do not conserve water so large
amount of dilute urine is excreted.
– Polydipsia
14. CONTD....
Central DI : Desmopressin
• Dose : oral- 100 microg TDS
: nasal -10-40 microgram / day
:1-4 microgram/day ( i.v , i.m, s.c)
Nephrogenic DI :
– Thiazides
– Carbamazepine
– Amiloride
15. CONTD...
2.Primary noctural enuresis :
• Intranasal desmopressin
• Fluid restriction
Dose : oral -200-400 microgram at bed time
: nasal 20-40 microgram
3. Post – lumbar puncture headache
16. Contd...
4. von Willebrand Disease:-
Desmopressin increase von willebrand
factor and factor VIII & ↓ the Bleeding Time.
Dose :
0.3-0.4 microgm/ kg slow i.v ( 15-30 min)
17. Adverse effects of ADH agonist
V1 receptor
( vasoconstriction )
V2 receptor
Facial pallor Fluid retention & water
intoxication
Nausea , abdominal cramps, urge
to defecate
Dilutional hyponatraemia
Angina Intranasl- ulceration & rhinits
C/I – in HT & I HD Allergy- urticaria & pruritis
Vasopressin, terlipressin desmopressin
18. ADH receptor antagonists
Why were antagonists developed?
1. To counteract V1a receptor mediated
effects when TPR ↑↑
2.To counteract V2 receptor mediated effects
when there is excessive reabsorption of
water.
3. V1a / V2 combination- diseases associated
with ↑ TPR & fluid retention like CHF.