know about your bed wet :p

1. Anti-diuretics
By
PRIYADHARSHINI [PD]

2. What are Anti-diuretics?
Substances that inhibit water excretion without
affecting salt excretion.
• Reduce urine output
• More precise term anti-aquaretics
• Primary indication - diabetes insipidus

3. Diabetes Insipidus

4. Drug classification
• Anti-diuretic hormone: ADH/Vasopressin,
Desmopressin, Lypressin, Terlipressin
• Thiazide Diuretics: amiloride
• Miscellaneous: indomethacin,
chlorpropamide, carbamazepine

5. ADH
• Synthesis: posterior pituitary secretes both
ADH and oxytocin.
• Regulation: osmoreceptors in hypothalamus
volume receptors in left atrium,
ventricles, pulmonary veins.
• Stimulus: rise in plasma osmolarity
contraction of ECF volume.
• Human form: 8-arginine-vasopressin.

6. ADH receptors
• G protein coupled cell membrane receptors
• Types: V1 and V2
• V1 receptors: all except on renal CD cells,
AscLH cells and vascular endothelium.
• Subtypes: V1a and V1b
• V1a: vascular, uterine, visceral smooth muscle,
adipose tissue, brain
• V1b: anterior pituitary, brain and pancreas.

7. • V2 receptor: more sensitive
• location:
• collecting duct in kidney: regulate water
permeability
• AscLH cells: activate Na/K/2Cl transporter
• vascular endothelium: vasodilator

8. Actions
• Kidney:
Acts on CD cells increase the permeability
Water gets absorbed concentrated urine
(hyperosmolar urine with same osmolarity of the
medulla)
• Blood vessels:
i. Constriction of blood vessels via v1 receptors
ii. Raises BP
iii. Prolonged exposure causes smooth muscle
hypertrophy.

9. Actions
• GIT:
Increased peristalsis
Evacuation and expulsion of gases
• Uterus:
i. Contraction due AVP acting on oxytocin
receptors.
ii. Increases sensitivity to oxytocin.

10. • CNS:
i. AVP doesn’t penetrate blood brain barrier
ii. Acts as a peptide neurotransmitter
iii. Regulation of temperature
iv. Systemic circulation
v. Task learning
vi. ACTH release

11. • Other uses:
• Platelet aggregation
• Hepatic glycogenolysis
• Coagulation factor VIII release
• Von willebrand’s factor release

12. Mechanism of action
• V2R:
• Principal cells of collecting duct: increased
aquaporins expression leading to increased
water absorption decreased urine formed.
• Increased vasopressin regulated urea
transporter expression in terminal CD cells
increased medullary hypertonicity
increased water absorption decreased
urine formed.

13. • V1R:
• Constricts vasa recta: diminished blood flow
to inner medulla; reduces washing off effect
and helps in maintaining high osmolarity;
contributing to antidiuresis.

15. AVP interactions
• Lithium, demelocycline; partially antagonise
AVP action (limit CAMP formation)
• NSAIDS (indomethacin): augments AVP
{increased renal PG synthesis}
• Carbamazepine, chlorpropamide: potentiates
AVP action on kidney.

17. AVP uses
• Based on V2 actions:
i. Diabetes insipidus
ii. Bedwetting in children
iii. Nocturia in adults
iv. Renal concentration test
v. Hemophilia, von willebrand’s disease
• Based on V1 actions:
i. Bleeding esophageal varices
ii. Before abdominal radiography

18. Adverse effects
• Transient headache
• Flushing
• Nasal irritation
• Congestion
• Belching
• Nausea
• Hyponatremia and fluid retention

19. Thiazides
• Paradoxical anti-diuretic effect in DI
• Short and brisk action
• Low efficacy
• Valuable in renal DI as AVP is ineffective
• Induce state of sustained electrolyte
depletion.
• Reduce GFR and fluid load
• Hydrochlorothiazide 25-50mg TDS

20. Other antidiuretics
• Amiloride: indomethacin
i. Drug of choice, reduce polyurea in renal DI.
ii. Reduces renal PG synthesis
• Chlorpropamide:
i. long acting sulphonylurea oral hypoglycemic
ii. Sensitizes the kidney to ADH action.
• Carbamazepine: anti-epileptic

21. Thank you