FOR MBBS/BDS as part of the CBME curriculum systemic Pharmacology (Drugs acting on Kidney)

1. DIURETICS
Dr.Arka Mondal
Assistant Professor

2. Introduction
 Diuresis:- ↑Urine volume
 Natriuresis:-↑Na excretion
 Kaliuresis:- ↑K excretion
 Diuretics:-drugs that ↑renal excretion of water & solutes (mainly Na
salt) to ↓fluid volume of the body & adjust the water electrolyte
balance
 Use for –
 Pathological condition like-
 Edema,
 CHF
 Renal disease
 Hypertension

4. Classification of diuretics
High efficacy/high-
ceiling/Loop
diuretics/
Inhibitors of
Na+K+2Cl - symport
 Furosemide
 Torsemide
 Bumetanide
Medium efficacy diuretics/
Inhibitors of Na+ Cl- symport
 Benzothiadiazines :-
Chlorothiazide,
Hydrochlorothiazide
Hydroflumethiazide
Benzthiazide
 Thiazide like-
Chlorthalidone,
Metolazone,
Xipamide
Indapamide
Clopamide
Low efficacy/weak diuretics
 Carbonic anhydrase
Inhibitors:-Acetazolamide
 Potassium sparing diuretics:-
 1. Aldosterone antagonist:
Spironolactone
Eplerenone
 2. Renal epithelial Na+
 channel inhibitors:-
Amiloride, Triamterene
 Osmotic diuretics:-
Mannitol, Glycerol, Isosorbide

5. CARBONIC ANHYDRASE INHIBITORS(CA-Inhibitors)
Drug-Acetazolamide, Methazolamide, Dorzolamide, Brinzolamide
Systemic
(oral route use as diuretics)
Topical
(Use in Glaucoma)
Acetazolamide, Methazolamide Dorzolamide, Brinzolamide
 Carbonic Anhydrase Enzyme-
 Distribution-Kidney, CNS, Eye, Gastric mucosa, Pancreas & RBC
 In kidney:-
 Present in luminal & basolateral membrane (membrane bound) & in cytoplasm of
proximal tubular epithelial cell(PCT)

6. :-
• Site of Action-PCT
Inhibit HCO3- reabsorption in the PCT(↓availability of H+ ion in PCT)
Also-
Inhibits Cl-,Na, Bicarbonate reabsorption →less water reabsorbed
Resulted-↑Na concentration in tubular fluid↔
Partially compensated by ↑NaCl reabsorption in later segments of tubule
thus its (low efficacy diuretics)
Inhibit both the membrane – bound and cytoplasmic forms of carbonic anhydrase
CA-inhibitors

7. Mechanism
of
Action:-

8. Other Actions:-
Aqueous humor:- ↓the rate of formation →consequently ↓ IOP
CSF:-↓ the rate of formation (sedation & paresthesia)
↑seizure threshold
Pharmacokinetics:-
Absorption-well orally (Acetazolamide)
t1/2-6-10hrs
Oral BA-100%
Excretion- unchanged in urine

9. Therapeutic Uses:-
Glaucoma- as adjuvant in narrow angle glaucoma (Local action so less
side effect)
Acute Mountain sickness(High altitude sickness)-
Above 10,000ft.
Symptoms:- Cerebral edema, Headache, Dizziness due to hypoxia
followed by respiratory alkalosis
℞-Tab. Acetazolamide-250 mg(prophylaxis)
24hr.before the ascent –cont.2days after returning to ground level
Mechanism:-
Acetazolamide→↓pH by metabolic acidosis which counteract
respiratory alkalosis

10. It ↑ventilation with acclimatization & maintain oxygenation
Familial periodic paralysis-
Occur due to sudden fall in plasma K+ level which is corrected by
Acetazolamide
Metabolic alkalosis:-
In Heart failure pt.→ alkalosis occur due to excessive use of diuretics
Preferred drug- Acetazolamide
Epilepsy:- in absence seizure as adjuvant
Acetazolamide→↑seizure threshold

11. Side effect:-
Hypokalemia-due to loss of K+
Acidosis
Renal Stone formation due to precipitation of calcium phosphate salts
in an alkaline urine
Drowsiness, paresthesia
Contraindications:-
Hepatic cirrhosis:- due to alkaline urine→ interfering with excretion of
ammonia
Acidosis or severe chronic obstructive pulmonary disease

12. OSMOTIC DIURETICS
Freely filtered at the glomerulus
Not reabsorbed by renal tubule
Relatively inert pharmacologically
Non – metabolizable
Increase plasma osmolarity
Currently available osmotic diuretics
-Mannitol, Glycerin, Isosorbide, Urea

13. Site of action: Proximal tubule , Descending loop of Henle
MOA:- Osmotic diuretics
↓
↑osmolarity of plasma & tubular fluid
↓
↑Urine volume
↓
↑Renal Blood Flow
↓
↓ Medullary hypertonicity → ↓ salt reabsorption
Acts by an osmotic effect in the tubules as non-re-absorbable solutes

14. In general, osmotic diuretics ↑↑ the urinary excretion of nearly all
electrolytes including Na+, K+, Ca 2+, Mg2+, Cl-, HCO3
- & phosphate
Mannitol→↓tubular water electrolyte reabsorption by following method
1.Due to osmotic effect-fluid is retained in the lumen of PT
2.Expand ECF- ↑Intravascular volume
↓
Draws water from the intracellular compartment to Ecf
↓
↑↑ GFR & hydrostatic pressure in glomerular capillaries & inhibit rennin release
↓
(↑urine volume)
3.↑renal blood flow→ Specially in medulla

15. -:Therapeutic Uses:-
In impending renal failure (e.g shock, ischemia, nephrotoxins,
Hemoglobinuria, myoglobinuria)→↑urine volume
Acute attacks of glaucoma-They draw fluid from eye, by osmotic
effect into blood
For short - term reductions in IOP (both pre-operatively and post-
operatively)
To reduce cerebral edema and brain mass (before and after
neurosurgery)
Head injury with ↑intracranial Tension→↓ICT
 To produce forced diuresis in case of poisoning (barbiturate)

16. -:Adverse Effects:-
Headache, nausea, vomiting
Loss of water in excess of electrolytes can cause hyponatremia and
dehydration
I.V. urea- Pain & thrombosis (site of administ.)
-:Contraindicated:-
 Anuria due to severe renal disease/ATN
 Heart failure / Acute LVF(left ventricular failure)-↑osmolality of ECF, may
produce pulmonary edema
 Cerebral hemorrhage

17. Na-K-2Cl SYMPORT
INHIBITORS
Also Called:
•Loop Diuretics
•High Ceiling Diuretics
Ethacrynic
Acid
(EDECRIN)
Torsemide
(DEMADEX)
Bumetanide
(BUMEX)
Furosemide
(LASIX)
 Process maximal Na+ excreting capacity when compared to thiazides &
potassium-sparing diuretics so called as “High ceiling Diuretics”

18. MOA:-
 Site of action:- thick ascending limb of loop of Henle
• Enter proximal tubule via organic acid transporter
• Inhibition of the apical Na+-K+-2Cl- cotransporter of the TALH
• Result:-
• ↓NaCl reabsorption
• ↓K+ Accumulation in cell
• ↓reabsorption of Mg/Ca
• ↑Mg++, Ca++ excretion-hypomagnesaemia
• Competition with Cl- ion for binding
• Stimulate renal PG synthesis→ NSAIDs interfere with
loop diuretics by ↓PG synthesis

20. Pharmacokinetics
• Absorption:-Rapid orally,
• BA- ranges from 65-100%
• Extensively bound to plasma proteins
• Furosemide and bumetanide-administered by oral, i.v., and i.m. routes.
• Torsemide is given orally
• Furosemide has a rapid onset of action—within 2–5 min of i.v.
• The duration of action of furosemide is short (4-6 hours)
• secreted by proximal tubule organic acid transporters
• Bumetanide-40 time more potent than furosemides
• Ethacrynic acid-100% BA

21. THERAPEUTIC EFFECTS
Increase Na Excretion
to 25% of Filtered Load
Treatment for
Oliguric Acute Renal Failure
Increase Ca Excretion
Treatment for
Hypercalcemia
Impair Free Water
Reabsorption
Increase Venous
Capacitance
Treatment for
Pulmonary Edema
Increase Urine Volume
Treatment for
Severe Edema
 Furosemides → Diuretic of Choice in pt. with severe renal failure (Acute + chronic)
IN CHF
↓pre-load due to potent
natriuretic &diuretic action

22. • Acute pulmonary oedema—loop diuretics act in the following way
I.V. furosemide
↑PG synthesis and release
↑Renal blood flow
↑Systemic venous capacitance
Results in shift of blood from central pulmonary to systemic vessels
↓left ventricular filling pressure
Produces quick relief from pulmonary oedema

23. ADVERSE EFFECTS
Hypomagnesemia
Metabolic
Alkalosis
Hypokalemia
Profound ECFV
Depletion
Hyperglycemia
Hyperuricemia
Ototoxicity
Hypocalcemia
Due to ↓Na+ absorption at PT
℞-
loop diuretic +K+-sparing diuretic
Ethacrynic Acid
↑ urinary excretion of Ca2+ and Mg2+
↓renal excretion of uric acid & may
precipitate attacks of gout
↓ insulin secretion

24. Contraindications:-
 Severe Na+ and volume depletion
 Hypersensitivity to sulfonamides
Drug interaction:-
 Loop diuretics × warfarin- Displacement of plasma protein binding of warfarin
 Loop diuretics × Li+ →clearance is decreased for Li
 Furosemide × aminoglycosides:- Both are ototoxic drugs(Additive effect)
 Furosemide ×Probenecid, NSAID’s → Inhibitors of organic acid transport (OAT-
1,3) →↓concentration in tubular fluid→ (↓uricosuric action of probenecid)

25. Na-Cl SYMPORT INHIBITORS
Also Called:
•Thiazide Diuretics
•Thiazide-Like Diuretics
Chlorthalidone
(HYGROTON)
Metolazone
(ZAROXOLYN)
Chlorothiazide
(DIURIL)
Hydrochlorothiazide
(HYDRODIURIL)

26. MECHANISM OF ACTION
• Site of action:-Early distal convoluted tubule (DCT)
• Thiazides freely filtered and secreted in proximal tubule
• Bind to the electroneutral Na-Cl cotransporter in renal cortex
• Thiazides impair Na+ and Cl- reabsorption in the early distal tubule:
“Medium efficacy” because 90% of filtered Na+ load is reabsorbed
before reaching the site of action of thiazide (DCT)
• Some of the thiazides also have weak carbonic anhydrase inhibitory
action and ↑HCO3
- loss (except-indapamide)
• ↑Ca++ reabsorption on DCT→ Because blocked of Na-Cl cotransporter
will enhance basolateral Na/Ca exchanger
• Thiazide action depends →On renal PG synthesis so (NSAIDs) ↓PG
synthesis will inhibit thiazide action

29. Pharmacokinetics
• Absorption- well orally
• BA-approx.100%
• Diuresis within one hour
• They have a long duration of action and are excreted in urine
• T1/2 for chlorothiazide is 1.5 hours, chlorthalidone 44 hours
– Whole Body Effects of Thiazides:-
– Increased urinary excretion of:
– Na+, Cl-,K+,Water,HCO3- (dependent on structure)
– ↓ ECF volume (contraction)
– ↓ blood pressure (lower CO)
– ↓ GFR

30. THERAPEUTIC EFFECTS
Increase Na Excretion
to 5-10% of Filtered Load
Treatment for
Hypertension(moderate-severe)
↓ Ca Excretion & ↑Ca
reabsorption
Treatment for
Calcium
Nephrolithiasis
Treatment for
Nephrogenic
Diabetes
Insipidus
Treatment for
Mild Edema
Due to diuretic effect &
Vasodilatory effect
↓Ca containing Kidney stone
Use along with loop diuretics in
severe resistant oedema
↓responsiveness of
ADH
Thiazides ↓urine vol. upto-50%
paradoxically

31. • “Thiazides used as Anti-diuretics in Diabetes insipidus” Explain
why..?
Possible Mechanism-
1.Paradoxical effect:-
Thiazides
↓↓
↓effective circulatory volume
↓↓
↓GFR
Due to which there is more reabsorption of water from kidney tubules
(Less excretion of Urine)

32. 2.
Thiazides
↓↓
inhibits cyclonucleotide phosphodiesterase Enzyme
↓↓
↑cAMP
↓↓
↑Permeability of collecting Duct towards water
↓↓
↓Volume of urine

33. ADVERSE EFFECTS
Hypomagnesemia
Metabolic
Alkalosis
Hypokalemia
ECFV
Depletion
Hyperglycemia
Hyperuricemia
Hyponatremia
Hypercalcemia
Impotence Increased LDL
Hyperlipidemia
Due to ↑thirst,
hypovolemia-induced
ADH elevation
Diluting effect
Rx-↓dose
↓water intake

34. • Drug interaction:-
• Thiazide × Digoxin, Li, Quinidine (due to hypokalaemia & increase
binding capacity of digoxine to Na+K+ATP-ase (leading to digoxin
toxicity)
• Thiazide + loop diuretics × Anti-coagulants, uricosuric drugs,
sulphonylurease & insulin-↓effect of those drugs
• Thiazide-like Diuretics:-
• Chlorthalidone:-
• Frequently used thiazide-like diuretic in hypertension as it has a
longest acting thiazide (48hr.)
• Indapamide:- more potent, longer acting and produce fewer adverse
effects than thiazides

35. • Use in hypertension.
• Metolazone:-
• More potent, longer acting and produce fewer adverse effects than
thiazides.
• Effective when GFR<20ml/min
• Dose:-2.5-10mg OD
• Xipamide:-
• Structurally related to chlorthalidone & frusemide

36. Na+ CHANNEL
INHIBITORS
Also Called:
•K-Sparing Diuretics
Amiloride
(MIDAMOR)
Triamterene
(DYRENIUM)

37.  Site of Action:-late collecting tubule & collecting duct
Mechanism of action:-
 Blockade of apical Na+ channel in the principal cells
 They directly block the Na+ channels in the luminal membrane of the cells of the
late DCT and CD leading to blocked of electrogenic entry of sodium causes a
drop in apical membrane potential (less negative), which is the driving force for
K+ secretion
 The net effect of these drugs is ↑Na+ excretion and retain potassium- hence these
are called K+-sparing diuretics.

39. Pharmacokinetics
• Triamterine
– 50% absorption of oral dose
– 60% bound to plasma proteins
– Extensive hepatic metabolism with active metabolites
– Secreted by proximal tubule via organic cation transporters
• Amiloride
– 50% absorption of oral dose
– not bound to plasma proteins
– not metabolized, excreted in urine unchanged
– Secreted by proximal tubular cation transporters

40. THERAPEUTIC EFFECTS
Enhance Natriuresis
Caused by Other Diuretics
Block Na Channels
Prevent Hypokalemia
Used in
Combination
with Loop &
Thiazide
Diuretics
Treatment for
Lithium-
Induced
Diabetes
Insipidus
-Amiloride augments
hydration of respiratory
secretions and thereby
improves mucociliary
clearance- cystic fibrosis

41. ADVERSE EFFECTS
Renal Stones
-least soluble
in urine
Hyperkalemia
Hyperkalemia
Amiloride
Triamterene
Headache, Nausea,
vomiting

42. MINERALOCORTICOID
RECEPTOR ANTAGONISTS
Also Called:
•K-Sparing Diuretics
•Aldosterone Antagonists
Spironolactone
Eplerenone

43. Spironolactone is an aldosterone antagonist
It is a synthetic steroid and structurally related to aldosterone
Aldosterone enters the cell and binds to specific mineralocorticoid
receptor (MR) in the cytoplasm of late distal tubule and collecting
duct (CD) cells
The hormone–receptor complex (MR–AL) enters the cell nucleus,
where it induces the synthesis of aldosterone-induced proteins
(AIPs)
The net effect of AIPs is to retain sodium and excrete potassium
Spironolactone competitively blocks the mineralocorticoid receptor
and prevents the formation of AIPs
Promotes Na+ excretion and K+ retention

44. Spironolactone is most effective
when circulating aldosterone levels
are high.
It also increases Ca2+ excretion
Low efficacy Diuretics-Mild ↑Na+ & Cl-
excretion

45. Pharmacokinetics
• Absorption:- 70% absorption in GI tract(oral BA-70-75%)
• Food-↑Absorption
• Distribution:-Extensively bound to plasma proteins-slow onset of
Action
• Metabolism:-Extensive first pass effect in liver and enterohepatic
circulation
• Active metabolite: Canrenone (active)-t1/2-17hr
• Excretion:-100% metabolites in urine

46. THERAPEUTIC EFFECTS
Enhances Natriuresis
Caused by Other Diuretics
Blocks Aldosterone
Treatment for
Primary Hyper-
aldosteronism
Prevents Hypokalemia
Used in
Combination
with Loop &
Thiazide
Diuretics
Treatment for
Edema of Liver
Cirrhosis
Treatment for
Hypertension
Treatment for
Heart Failure
Hirsutism &
PCOD
Due to antiandrogenic
action

47. ADVERSE EFFECTS
Impotence
Gynecomastia
Metabolic
Acidosis
Hyperkalemia
CNS Side
Effects
Peptic Ulcers
Gastritis
Menstrual
Irregularities
Deepening of
Voice
 ↑Testosterone clearance
 Covert Testosterone to estradiol
 Inhibit androgen production
Inhibition of
H+ secretion

48. IMPORTANT DRUG INTERACTIONS:-
 ACE Inhibitors× spironolactone→ dangerous Hyperkalemia
 NSAID’s × spironolactone → ↓action of spironolactone
Eplerenone:-
 More selective aldosterone antagonist
 less estrogenic A/E → low affinity for androgen receptor
 Potent CYP3A4-inibitors
 Well absorbed orally
 Metabolism-liver
 USE:- Hypertension, CHF

49. ANTI-DIURETIC DRUGS

50. • Antidiuretics→ drugs that ↓ urine volume
• “Anti-Aquaretics”→inhibit water excretion without affecting salt excretion
ANTI-DIURETICS
 Vasopressin (ADH)
 Desmopressin
 Lypressin
 Terlipressin
Antidiuretic hormone &
its analogues  Thiazides
 Amiloride
Natriuretics
 Carbamazepine
 Chlorpropamide
 Indomethacin
Miscellaneous

51. • VASOPRESSIN(ADH):-
• Poly-peptide hormone consisting of nine amino acid
• synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and
stored in posterior pituitary
• Stimulated by ↑plasma osmolality (due to H20 loss & ↑Na concentration)
• Structurally similar to oxytocin & process cross biological activity like
contraction of smooth muscle of uterus, as well as the GIT
• ADH cause→↑permeability of the collecting ducts & distal tubules to water
• Result→↑reabsorption of water by nephrons
• T1/2- 15-20min
• ADH (Vasopressin) receptors:-
V1-receptor V2-receptor

52. V1-receptor V2-receptor
Vasopressin Receptor
V1a V1b
Also called V3
 Distribution:-
Renal medullary interstitial
cells
Vasa recta, platelets, spleen,
testis
Renal cortical CD
Myometrium, Adipocytes,
Platelets
Distribution:-
Anterior pituitary,
Certain areas in
brain,Pancreas
 Distribution:-
Principal cells of
collecting ducts (CDs)
in the kidney
More sensitive to
ADH than V1

53. Pharmacological Action of Vasopressin
V1 receptors
 V1a-mediated:-
• Blood vessels: Vasoconstriction
• GIT: Increases peristalsis
• Liver: Glycogenolysis
• Platelets: Aggregation
 V1b-mediated:-
• CNS: Release of ACTH from
anterior pituitary
V2 receptors:-
• ↑H20 permeability (↑ H20
reabsorption) in CD-↓ urinary
output
• Blood vessel-Vasodilatation
(Release NO)
• Release of clotting factor VIII &
Von Willebrand’s factor from
vascular endothelium

54. Drugs Affecting The renal actions of Vasopressin
Drugs ↑ Antidiuretic
response
 NSAIDS- Indomethacin
 Carbamazepine,
 Chlorpropamide,
 Clofibrate
Drugs ↓ Antidiuretic
response
 Lithium
 Demeclocycline
 Ethanol
Pharmacokinetics:-
 Inactive orally (Destroyed) by proteolytic Enzyme→ administered parentally
(i.m.,i.v.,s.c. or intranasal)
 Metabolized rapidly in liver

55. Vasopressin Analogues
• Desmopressin:-
• Selective V2 receptor agonist (Synthetic analogue)
• 10 time More potent than vasopressin-antidiuretic
• It has negligible V1 receptor mediated vasoconstrictor action
• It is administered by oral, nasal and parenteral routes
• t1/2 is 2hr. but duration of action is longer-10hr.
• DOC in Central diabetic insipidus(i.m./S.c., intranasally)
• Dose- 0.3-0.6 orally
• Lypressin:-
• It acts on both V1 and V2 receptors (Non-selective agonist)
• It is less potent but longer acting
• USE:-Oesophageal varices

56. • Terlipressin:-
• Prodrug of vasopressin with selective V1 action
• i.v. administration
• Less toxic than lypressin
• Use:- oesophageal varices-control bleeding
-:Therapeutic uses of Vasopressin Analogues:-
• 1. For emergency control of bleeding esophageal varices:
• Terlipressin is preferred (Safer)
• Action:- Terlipressin
↓↓
acts on V1 receptor n constricts mesenteric blood vessels
↓↓
↓↓ blood flow to portal vessels through liver

57. ↓↓ pressure in the varices n stops bleeding
• 2. Vasopressin used before abdominal radiography to expel intestinal gas by
acting on V1 receptor in the intestine
• 3.Abdominal surgery in pt. with Portal hypertension →↓hemorrhage
• 4.Acute hemorrhagic gastritis →↓hemorrhage (V1 mediated vasoconstriction of
gastric vascular bed)
• 5. Central DI (Neurogenic)- Due to ↓↓ ADH secretion,
• Desmopressin-↓urine volume & well tolerated, Long acting
• 6.Primary nocturnal enuresis- Desmopressin (intranasally)+ restricted fluid
intake at bed time
• 7. Hemophilia and von Willebrand’s disease – i.v. Desmopressin, →controls
bleeding by promoting release of factor VIII and von Willebrand’s factor (by
acting on V2 receptors

58. • Adverse Effects of Vasopressin Analogues:-
• 1. Nausea, vomiting, diarrhoea, belching and abdominal cramps.
• 2. Backache→ is due to uterine contraction.
• 3. Vasopressin can precipitate an attack of angina by constricting coronary blood
vessels
• 4. Local irritation and ulceration due to Intranasal desmopressin use
• 5. Fluid retention and hyponatremia can occur (V2-mediated)
• 6.It should not be given to patients with acute renal failure
 ADH receptor Antagonist:-
 Vaptans like Conivaptans, Tolvaptan, Relcovaptan, Mozavaptan, Lixivaptan,
Satavaptan
 Tolvaptan:- orally effective non-peptide selective V2 blockers

59. • Metabolism- by CYP3A4
• T1/2-6-8hr.
• USE:-
 Hyponatraemia due to CHF-short term benefit by ↑water clearance by kidney
 Liver cirrhosis
 Syndrome of inappropriate ADH secretion (SIADH)
• A/E- thirst and dry mouth, fever.,g.i. upset and hyperglycaemia
• Conivaptan:-
• V1a,V2 blockers
 First non peptide antagonist approved for SIADH

60. Disease due to altered Vasopressin secretion/response
1. Diabetes Insipidus:-
• 1A.Central(neurogenic or pituitary) DI:- due to ↓ADH secretion
• It may be idiopathic
• Urine production-30ml/kg (low osmolality)
• Symptoms- Polydipsia
• Treatment:-(℞) life long
• DOC-Desmopressin –Intranasal -5mcg BD
• Other drugs:-
Chlorpropamide:- ↑Antidiuretic effect of ADH on kidney by V2 receptor action
Carbamazepine:-↓urine volume in high dose
Thiazides-due to paradoxical effect

61. • 1B.Nephrogenic DI:-
• ADH levels are normal, but renal tubules (CD) fail to respond to ADH
• Result due to defect in V2 receptor
• Congenital or Acquired(head injury & neurosurgery)
• Drug Induced- Li, Demeclocycline, Clozapine
• Treatment:-
• Thiazide –due to paradoxical effect
• Amiloride- lithium-induced nephrogenic DI (inhibit Li & Na entry into the renal
epithelial cells)
• Indomethacin→ ↓urine volume by inhibiting renal PG synthesis
2.SIADH:- (Syndrome of Inappropriate secretion of ADH)
 Excess secretion of ADH
 Impaired water excretion along with hyponatremia and low plasma osmolality

62. • Symptoms –
• Anorexia, nausea, vomiting, muscle cramps, lethargy, coma, convulsions &
death
• Treatment(℞):-
• 1. Restricted water intake
• 2. Drugs:-
Demeclocycline:- inhibits action of ADH in the CD
 Dose-600-1200mg OD
Vasopressin receptor antagonists:-
 Conivaptan-i.v. (V1a/V2) and tolvaptan-(orally) (V2 selective)

63. Thank You