ADH is a peptide hormone synthesized in the hypothalamus and stored in the posterior pituitary. It is released in response to falling blood pressure, increases in plasma osmolality, and severe hypovolemia or hypotension. ADH acts through three receptor types, V1a, V1b, and V2. The V1a receptor mediates vasoconstriction while the V2 receptor mediates the antidiuretic effect of ADH by increasing water reabsorption in the renal collecting ducts. Desmopressin is a synthetic analog of ADH used to treat diabetes insipidus, nocturnal enuresis, hemophilia, and Von Willebrand's

1. By:Awgichew Shewasinad
[Bpharm,M.Sc.Pharmacology]
Anti-Diuretic Hormone and Drugs
Targeting ADH Receptors

2. Anitdiuretic Hormone/Vasopressin
2
 ADH is a peptide hormone synthesized in the
hypothalamus and stored in the posterior pituitary
 Released from the pituitary in response
− to falling BP
− increase in plasma osmolality
− Severe hypovolemia/hypotension
6/3/2022

3. ADH….
 The antidiuretic mechanism in mammals involves two
anatomical components:
− a CNS component for the synthesis, transport, storage,
and release of vasopressin, and
− a renal collecting-duct system composed of epithelial
cells that respond to vasopressin by increasing their
permeability to water.
3 6/3/2022

4. ADH….
 a neurotransmitter; among its actions in the CNS are
apparent roles in the secretion of ACTH and in the
regulation of the CVS, temperature, and other
 also may play a role in hemostasis by promoting the release
of coagulation factors by the vascular endothelium and
increasing platelet aggregation.
4 6/3/2022

5. Vasopressin receptors
 Vasopressin receptors are GPCRs
 3 types of receptors, V1a, V1b, and V2.
V1a receptor
 is the most widespread subtype of vasopressin receptor;
 found in vascular smooth muscle, the adrenal gland,
myometrium, the bladder, adipocytes, hepatocytes, platelets,
renal medullary interstitial cells, vasa recta in the renal
microcirculation, epithelial cells in the renal cortical collecting-
duct, spleen, testis, and many CNS structures. 6/3/2022
5

6. Vasopressin receptors ……
V1b receptors
 have a more limited distribution and are found in the anterior
pituitary, several brain regions, the pancreas, and the
adrenal medulla.
V2 receptors
 are located predominantly in principal cells of the renal
collecting-duct system but also are present on epithelial
cells in the thick ascending limb and on vascular endothelial
cells
6 6/3/2022

7. Vasopressin receptors ……
 V1a receptors mediate the vasoconstrictor
action of vasopressin;
 V2 receptors mediate the antidiuretic action
7 6/3/2022

8. ADH…….
• ADH acts as non-adrenergic peripheral vasoconstrictor
• Concentrate urine by ↑g reabsorption of water by the renal
tubules
• Anitdiuretic effect is mediated by V2 receptors located in
DCT & CT
• At supra-anitdiuretic doses, it causes direct stimulation of V1
receptors in the vascular smooth muscles
 ADH causes by activating on V1 receptors
 Vasoconstriction
 Platelet aggregation
6/3/2022
8

9. ADH ….
9
 ADH, via extrarenal V2-like receptors, regulate the
release of coagulation factor VIII and Von Willebrand
factor……role in hemostasis
 Desmopressin is a long-acting synthetic analog of ADH
with minimal V1 activity and an antidiuretic-to-pressor
ratio 4000 times that of vasopressin
6/3/2022

10. ADH ….
10
Pharmacokinetics
 Vasopressin is inactive by PO, like other peptides (IV
or IM)
 Eliminated by renal and hepatic metabolism.
 Desmopressin can be administered IV, SC,
intranasally, or orally
6/3/2022

11. Indications:Vasopressin and desmopressin
 Primary diabetes insipidus
 Polyuria, polydipsia, or hypernatremia
 Nocturnal enuresis, bedtime desmopressin therapy,
decrease nocturnal urination
 Vasopressin infusion is effective in some cases of
bleeding
 Desmopressin is also used for the treatment of
coagulopathy in hemophilia A and (Factor VIII
deficiency) Von Willebrand's disease
 Used in preparation for minor surgery such as tooth
extraction
6/3/2022
11

12. Toxicities
 Headache, nausea, abdominal cramps, agitation, and
allergic reactions occur rarely
 Therapy can result in hyponatremia
 Water intoxication
 Vasopressin (but not desmopressin) can cause severe
vasoconstriction & should be used cautiously in patients
with CAD
6/3/2022
12

13. 13
I Thank You
6/3/2022