This document discusses various anti-diuretic agents including antidiuretic hormone (ADH or vasopressin), its synthesis and release mechanisms. It classifies anti-diuretic agents into antidiuretic hormone, thiazide diuretics, and miscellaneous agents. It describes the pharmacological actions of ADH including its effects on kidneys to increase water permeability and reduce urine volume, and its effects on blood vessels and other tissues. It also discusses analogues of ADH including lypressin, terlipressin, and desmopressin, and their uses, pharmacokinetics, and adverse effects. Thiazide diuretics and some other miscellaneous drugs that provide alternative anti

1. Pharmacology
By-
Dr. Mrunal R. Akre

2. Anti-diuretic

3. Antidiuretic
 Antidiuretics (more precisely ‘anti-
aquaretics’, because they inhibit water
excretion without affecting salt excretion)
are drugs that reduce urine volume,
particularly in diabetes insipidus (DI)
which is their primary indication.

4. Classification of Anti diuretic
Agents:
 Antidiuretic hormone:-
(ADH,Vasopressin),Desmopressin,Lypressin,
Terlipressin
 Thiazide diuretics: Amiloride.
 Miscellaneous: Indomethacin, Chlorpropamide,
Carbamazepine

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

6. 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.

7.  ANTIDIURETIC HORMONE (Argenine Vasopressin-AVP)
◦ It is a nonapeptide secreted by posterior pituitary (neurohypophysis) along with
oxytocin.
◦ It is synthesized in the hypothalamic (supraoptic and paraventricular) nerve cell
bodies as a large precursor peptide along with its binding protein
‘neurophysin’.
◦ Both are transported down the axons to the nerve endings in the median
eminence and pars nervosa.
◦ Osmoreceptors present in hypothalamus and volume receptors present in left
atrium, ventricles and pulmonary veins primarily regulate the rate of ADH
release governed by body hydration.
 Actions
◦ Kidney -AVP acts on the collecting duct (CD) principal cells to increase their
water permeability— water from the duct lumen diffuses to the interstitium by
equilibrating with the hyperosmolar renal medulla
◦ Mechanism of action
 Vasopressin is instrumental in rapid adjustments of water excretion according to the
state of body hydration, as well as in dealing with conditions prevailing over longterm
 Pharmacokinetics
 AVP is inactive orally because it is destroyed by trypsin. It can be
administered by any parenteral route or by intranasal application.
plasma t½ is short ~25 min. However, the action of aqueous
vasopressin lasts 3–4 hours.
 TM- Aqueous vasopressin (AVP) inj: POSTACTON 10 U inj; for i.v.,
i.m. or s.c. administration.

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

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

10. PHARMACOLOGICAL ACTIONS OF
ADH/AVP ( VASOPRESSIN)
 2. Blood Vessels:
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

11. PHARMACOKINETICS OF ADH/AVP (
VASOPRESSIN)
 Absorption- Orally inactive because
destroyed by trypsin
 Metabolism- Liver
 Excretion- Kidney
 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.

12.  VASOPRESSIN ANALOGUES
◦ Lypressin
 It is 8-lysine vasopressin.
 Though somewhat less potent than AVP, it acts on both V1 and V2 receptors
and has longer duration of action (4–6 hours).
 It is being used in place of AVP—mostly for V1 receptor mediated actions.
 TM- PETRESIN, VASOPIN 20 IU/ml inj; 10 IU i.m. or s.c. or 20 IU diluted in
100–200 ml of dextrose solution and infused i.v. over 10–20 min.
◦ Terlipressin
 This synthetic prodrug of vasopressin is specifically used for bleeding
esophageal varices; may produce less severe adverse effects than lypressin.
 Dose: 2 mg i.v., repeat 1–2 mg every 4–6 hours as needed.
 TM- GLYPRESSIN 1 mg freeze dried powder with 5 ml diluent for inj, T-
PRESSIN, TERLINIS 1 mg/10 ml inj.
◦ Desmopressin (dDAVP)
 This synthetic peptide is a selective V2 agonist; 12 times more potent
antidiuretic than AVP, but has negligible vasoconstrictor activity.
 Dose: Intranasal: Adults 10–40 μg/day in 2–3 divided doses, children 5–10 μg
at bed time. Oral: 0.1–0.2 mg TDS. Parenteral (s.c. or i.v.) 2–4 μg/day in 2–3
divided doses.
 TM- MINIRIN 100 μg/ml nasal spray (10 μg per actuation); 100 μg/ml
intranasal solution in 2.5 ml bottle with applicator; 0.1 mg tablets; 4 μg/ml inj.
◦ Uses
 A. Based on V2 actions (Desmopressin is the drug of choice)
 Diabetes insipidus, Bedwetting in children and nocturia in Adults, Haemophilia, von
Willebrand’s disease

13. USES
 A. Based on V2 action:
◦ Diabetes insipidus (DI)- DI of pituitary origin
(neurogenic) important indication for vasopressin but
ineffective in renal DI (nephrogenic).
◦ Bedwetting in children & nocturia in adults-
Desmopressin reduce urine volume resulting control
nocturia condition.
◦ Renal concentration test- 5-10 U i/m causes maximum
urine retention and urine concentration.
◦ 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:
◦ Bleeding esophageal varices: Vasopressin stops the
bleeding by constricting mesenteric blood vesscles and
reducing blood flow though liver & allowing clot formation.
◦ Before abdominal radiography: Lypressin used to drive
out gases form bowel facilitate easy abdominal radiography.

14.  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

15. 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.

16. 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

17. To be continued……..