Antidiuretics

1. ANTIDIURETCS
Name-Manish Baghel
Roll No-64

2. INTRODUCTION
 Definition: These are drugs that reduce urine volume.
 Specially used in condition like diabetes insipidus (DI).
 Classification of Anti diuretic Agents:
 1 Antidiuretic hormone:
(ADH,Vasopressin),Desmopressin,Lypressin,
Terlipressin
2 Thiazide diuretics: Amiloride.
3 Miscellaneous: Indomethacin, Chlorpropamide,
Carbamazepine

3. 1. ANTIDIURETIC HORMONE: SYNTHESIS &
RELEASE OF ADH
Stimuli (rise in plasma osmolarity and Contraction of extra
cellular fluid)
Generate Impulse from
baroreceptor
Posterior pituitary gland secrete ADH
Hypothalamus nerve cell bodies synthesize ADH along with
protein Neurophysin
Transported to nerve endings in median eminence & pars nervosa
Osmoreceptor- Hypothalamus & Volume receptor- Left atrium,
ventricles & pulmonary veins primarily regulate the rate of ADH
release

4. ADH/AVP ( VASOPRESSIN) RECEPTOR DISTRIBUTION:
G protein coupled cell membrane receptors: Two subtypes
A) V1 receptors - Function mainly through phospholipase
C-IP3/DAG pathway Release Ca+ Cause
vasoconstriction, visceral smooth muscle contraction,
glycogenolysis. Platelet aggregation, ACTH release.
1.V1a- Present on vascular and other smooth muscles
platelets, liver.
2.V1b- Localized to the anterior pituitary.
B) V2 receptors- Present on collecting duct (CD) cells in the
kidney regulate their water permeability through
CAMP production.

5. PHARMACOLOGICAL ACTIONS OF ADH/AVP ( VASOPRESSIN)
1. Kidney:
ADH
Collecting
Duct Cells
Acts
on
Increase
water
permeability
Lumen Water
diffuse to
interstitium
Mechanism of Action
1
V2 receptor on
basolateral side of CD
cell membrane
Increases
cAMP
formation
Activatio
n
Causes
Activatio
n
Depend on
Protein
kinase A
Phosphorylation of relevant protein promote exocytosis of
auaporin 2 water channel containing vesicles in apical
membrane
More aqueous channels inserted in to apical
membrane
Water permeability of CD cell increased and prevent
urination

6. Mechanism of Action
2
V1 receptor action of
ADH
Constrict Vasa Recta
Diminish blood flow to inner
medula
Prevent Urine
formation
PHARMACOLOGICAL ACTIONS OF ADH/AVP ( VASOPRESSIN)
Dehydration ADH release
Over hydration ADH inhibited.

7. 2. Blood Vessels:
PHARMACOLOGICAL ACTIONS OF ADH/AVP ( VASOPRESSIN)
ADH acts on V1
receptor
Constriction of blood vessels ( Hence name
Vasopressin)
Increases blood
pressure
2. Other action:
•Smooth muscles- Constricted
•Gut- Increased peristalsis, evacuation and expulsion of
gases
•Uterus- Constricted
•CNS- ADH not penetrate BBB
•Lever- Glyconeogenesis

8.  Absorption- Orally inactive because destroyed by
trypsin
 Metabolism- Liver
 Excretion- Kidney
PHARMACOKINETICS OF ADH/AVP ( VASOPRESSIN)
ANALOGUES OF ADH/AVP ( VASOPRESSIN)
 Lypressin- 8-lysin analogues; acts on both receptor; longer
duration of action;
 Terlipressin- Synthetic prodrug; mainly used for bleeding
esophageal varices.
 Desmopressin- Synthetic peptide; selective V2 agonist;
12times more potent than all;
But produces systemic side effects which are overcomes
by nasal application.

9. USES:
A. Based on V2 action:
1.Diabetes insipidus (DI)- DI of pituitary origin (neurogenic)
important indication for vasopressin but ineffective in renal DI
(nephrogenic).
2. Bedwetting in children & nocturia in adults- Desmopressin reduce
urine volume resulting control nocturia condition.
3.Renal concentration test- 5-10 U i/m causes maximum urine
retention and urine concentration.
4.Haemophilia, Von Willebrand’s disease- It is genetic disorder where
missing or defective vonWillebrand factor (VWF), a clotting protein
is observed. While ADP releases clotting factor.
B. Based on V1 action:
1.Bleeding esophageal varices: Vasopressin stops the bleeding by
constricting mesenteric blood vesscles and reducing blood flow
though liver & allowing clot formation.
2.Before abdominal radiography: Lypressin used to drive out gases
form bowel facilitate easy abdominal radiography.

10. ADVERSE DRUG EFFECT:
Vasopressin, lypressin or terlipressin are nonselsctive derivatives so
shows more side effects as compaire to desmopressin (V2 selective).
• Transient headache and flusing- common.
• Nasal irritation, congestion, rhinitis, ulceration and epistaxis(nose
bleeding)
• Systemic effects- belching, nausea, abdominal cramps, pallor, urge to
defecate, backache in females (due to uterine contraction).
• Fluid retention and hyponatraemia.
• ADP causes bradycardia, increase cardiac afterload and precipitate
angina by constricting coronary vessels.
CONTRAINDICATION:
• Patients with;
• Ischemic heart disease,
• Hypertension,
• chronic nephritis
• psychogenic polydipsia.
• Urticaria and other allergies

11. 2.THIAZIDES DERIVATIVES:
Actually thiazide and high ceiling diuretics are diuretic drug but which
provides antidiuretic effect in Diabetes insipidus. high ceiling
diuretics are not used because is having short and strong action.
Thiazides reduce urine volume in both pituitary origin and renal
Diabetes insipidus.
Used when ADH is ineffective.
Mechanism of Action
Actual mechanism is unknown; But thiazides may
Induce sustained electrolyte depletion resulting Glomerular filtrate
completely reabsorbed Continuous electrolyte loss causes
decreases plasma osmolarity Antidiuretic action.
Thiazides reduces g.f.r. and produce fluid load on tubules.

12. 3. MISCELLANEOUS DERIVATIVES:
These all are supportive derivatives for antidiuretic activity:
Amloride hydrochloride is a pyrazine-carbonyl-guanidine it is a drug of
choice for lithium induced nephrogenic Diabetes insipidus.
Indomethacin: Reduce polyuria in renal Diabetes insipidus.
Chlorpropamide: It sensitizes ADH to acts on kidney cells.
Carbamazepine

13. REFERENCE