This document discusses different classes of diuretic drugs. It describes the mechanisms and sites of action of high ceiling loop diuretics like furosemide, medium efficacy thiazide diuretics, carbonic anhydrase inhibitors, potassium sparing diuretics, and osmotic diuretics like mannitol. Adverse effects and clinical uses are provided for each class. The major functions of the kidney and sites of sodium reabsorption are also reviewed.

1. DIURETICS
BYBY
MR. V P PATILMR. V P PATIL
ASST. PROF.ASST. PROF.
DEPT. OF PHARMACOLOGYDEPT. OF PHARMACOLOGY
BLDEA’SBLDEA’S
SSM COLLEGE OF PHARMACY AND RESEARCHSSM COLLEGE OF PHARMACY AND RESEARCH
CENTRE.CENTRE.
VIJAYAPUR.VIJAYAPUR.

2. Diuretics

3. 1. Major Functions of The Kidney
• Regulation of osmolarity of the body fluid
• Regulating the volume of the extracellular fluid
• Regulating concentrations of electrolytes of the
extracellular fluid
• Regulation of acid-base balance
• Clearance of metabolic waste products (urea, uric acid,
creatinine)
• Production of special substances (erythropoietin, renin,
prostaglandins, and thromboxane)

5.  Diuretics are the drugs which causes net loss
of Na + and water in urine by inhibiting
reabsorption of Na+ & water.
 Normally sodium is reabsorbed ---
~ 65 % in PCT
~ 20 % in As Loop of Henle
~ 10 % in DCT
~ 5 % in CD

6. 65 %
10%
20 %
5 %

7. Diuretics
 High efficacy ( High ceiling diuretics):
( Inhibitors of Na+
K+2Cl Co-transport )
 Sulphamoyl deri - Furosemide, Bumetanide,
 Phenoxy acetic acid deri - Ethacrynic acid
 Organomercurials - Mersalyl
 Medium efficacy :
( Inhibitors of Na-Cl Co-transport )
Hydrochlorothiazide, Benzthiazide,
Metazolone

8. Diuretics
Weak or adjuvant diuretics :
 Carbonic anhydrase inhibitors :
Acetazolamide
 Potassium sparing diuretics :
 Aldosterone antagonist : Spironolactone
 Directly acting (Inhibitors of renal epithelial Na
channel) : Triamterene , Amiloride
 Osmotic diuretics : Mannitol

9. Diuretics
High ceiling loop diuretics : Furosemide
(Inhibitors of Na+ K+ 2Cl Co-transport) :
-- Major action on thick Ascending loop of
Henle
-- Diuretic response can be increased to 10 L of
urine
-- It is active in patients with severe renal
failure

10. Furosemide

11. Diuretics
Furosemide :
 Minor action on PCT – weak carbonic
anhydrase activity – excretion of HCO3-
 I.V cause increase in systemic venous
capacitance and decrease left ventricular filling
pressure.

12. Diuretics
Furosemide
 Furosemide increases calcium excretion
{thiazides decrease calcium excretion}
 It increase the plasma uric acid levels by
decreasing renal excretion – interference with
tubular secretion and reabsorption.
 Hyperglycemia is seen with loop diuretics.

13. Furosemide
Hypokalemia, Hearing loss, Hyperuricemia, Hyperglycemia
Hypocalcemia
Interactions:
1.Furosemide + ACE-I ---Antihypertensive action potentiated
2. - + NSAIDS --- Loss of diuretic effect
3. - + Aminoglycosides --- ototoxicity
4. - + Li --- Li toxicity
Dose: Furosemide – 20-80mg once daily in morning
Diuretics

14. Diuretics
High ceiling loop diuretics :
(Inhibitors of Na+ K+ 2Cl Co-transport) :
Bumetanide : It is 40 times more potent than
furosemide .
Ethacrynic acid : similar to furosemide
It is an irritant – orally it produces diarrhea.
It is toxic and can cause hearing loss and
hepatotoxicity.

15. Diuretics
Uses of high ceiling diuretics :
 Edema
 Heart failure
 Acute pulmonary edema
 Hypertension
 Hypercalcemia

16. Diuretics
Inhibitors of Na+ / Cl - symport :
Hydrochlorothiazide , Metazolone, Indapamide
 The primary site of action is cortical diluting
segment or early distal tubule.
 Secondary action is CA inhibition in PCT.

17. Diuretics
Inhibitors of Na+ /Cl - symport : Thiazides :
 Increased urinary Na+, Cl-, K+
and Mg++
excretion
 Weak CAase inhibition – excretion of HCO3
 Uric acid excretion, Ca++
 Moderately efficacy as 90% of Na+ is reabsorbed before it
reaches DCT
 They decrease blood pressure and increase blood sugar.
 They are not effective in low GFR.

18. Re
es DCT
---------- ----------

19. Diuretics
Adverse effects of thiazides diuretics :
 Hypokalemia
 Hearing loss
 Hyperuricemia – ppt of gout
 Hyperglycemia
 Hypercalcemia
Contraindications:
 Hypokalemia, Ventricular arrhythmia, Volume
depleted states

20. Diuretics
Thiazides : Interactions
 Thiazides + Steroids, Estrogen –-- Anagonism of diuretic action
 - + Li --- Li toxicity
 - + Aminoglycosides --- Nephrotoxicity
Dose: Chlorthalidone – 12.5mg-25mg, Indapamide - 20mg
Uses :
 Edema
 Hypertension

21. Diuretics
Carbonic anhydrase inhibitors :
 CA is an enzyme which catalyzes the reversible
reaction
H20 +CO2 «-------------» H2CO3.
 Carbonic acid ionizes into HCO3 and H+, thus
helps in the transport of CO2 and H+
secretion.
 The CA enzyme is present in the renal tubular
cells, gastric mucosa, pancreas, ciliary body
and RBC.

23. Diuretics
Carbonic anhydrase inhibitors : Acetazolamide
 The net effect is inhibition of HCO3
reabsorption in PCT.
 The secretion of H+ is inhibited.
 The urine produced is rich in bicarbonate --
alkaline urine – depletes body of HCO3----
producing acidosis.

24. Diuretics
Carbonic anhydrase inhibitors :
Extra – renal actions :
 Lowering of intraocular tension due to
decreased formation of aqueous humor.
 Decreased gastric acid and bicarbonate
secretion.

25. Diuretics
CAase inhibitors : Acetazolamide :
adverse effects :
 Acidosis, hypokalemia,
Dose: Acetazolamide – 250mg – 1000mg/d
Uses :
 Glaucoma
 To alkalinize urine
 In aspirin poisoning – Alkalinizes urine
 Acute mountain sickness(↓ collection of fluid in lungs
climbers)

26. Diuretics
Potassium Sparing Diuretics :
 Aldosterone antagonists – Spironolactone.
 Na+ channel inhibitors -- Amiloride,
Triamterene.

28. Diuretics
Potassium Sparing Diuretics :
 Spironolactone : Aldosterone antagonists
 Aldosterone acts by combining with
intracellular receptors --- induces formation
of proteins – which promotes reabsorption
of Na+ and secretion of K+
 It increases calcium excretion by direct
action on the tubules
 Action is dependent on aldosterone

29. Diuretics
Potassium Sparing Diuretics :
Spironolactone :
 oral bioavailability ~75 %
 ↑ excretion of Na+, Cl-
 ↓ excretion of K+, H+, Ca++ Mg++
 Converted into metabolite – canrenone

30. Diuretics
Potassium Sparing Diuretics :
 Spironolactone :
adverse effects
 Gynaecomastia, menstrual irregularities,
impotence, hyperkalemia.
Uses
 It is a weak diuretic – more useful in cirrhotic,
nephrotic and refractory edema
 It is used to counteract the K+ loss due to
thiazides and loop diuretics

31. Diuretics
Renal epithelial Na+ channel inhibitors :
Triamterene, Amiloride
 Non-steroidal in nature
 Action is similar to spironolactone – but
independent of aldosterone
 Acts by inhibiting Na channels of the DT and
CD

32. Diuretics
Renal epithelial Na+ channel inhibitors :
Triamterene, Amiloride
 Both are used in conjunction with thiazides
and loop diuretics
 Hyperkalemia occurs when used with ACE
inhibitors.

33. Diuretics
Renal epithelial Na+ channel inhibitors :
Amiloride :
 10 times more potent than the triamterene
 It decreases calcium excretion and increases
urate excretion
 Half life ~ 15 hrs
 Blocks entry of lithium into renal cells and
mitigate DI caused by lithium

35. Diuretics
Mannitol: Osmotic diuretics :
 It is a non-electrolyte – pharmacologically
inert
 Not metabolized, freely filtered in the
glomerulus, undergoes limited reabsorption
 Inhibits water and electrolyte reabsorption

36. Diuretics
Mannitol: Osmotic diuretics :
 Expands extracellular fluid and increases GFR
 Increases renal blood flow - salt reabsorption is
reduced
 Primary action is to increase urinary volume
 Not absorbed orally – given I.V

37. Diuretics
Mannitol: Osmotic diuretics : Uses
 To maintain GFR and urine flow in renal
failure
 Forced diuresis in poisoning
 To reduced IOT – by its osmotic activity