This document provides information on diuretic drugs, including their mechanisms and sites of action, indications for use, and adverse effects. It discusses loop diuretics like furosemide and bumetanide that act in the thick ascending loop of Henle, thiazide diuretics like hydrochlorothiazide that act in the distal tubule, and potassium-sparing diuretics like amiloride and spironolactone that act in the collecting ducts. It also covers carbonic anhydrase inhibitors and osmotic diuretics. Non-diuretic uses and combinations with other drugs are mentioned. Resistance, interactions, and specific adverse effects are summarized for each drug class.

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

2.  DIRECTLY ACTING
A) Acting on thick ascending loop of henle-
FUROSEMIDE, BUMETANIDE, TORSEMIDE,
PIRETANIDE,ETHACRYNIC ACID,
INDACRINONE(uricosuric drug)
B) Acting on proximal part of distal tubule
THIAZIDE group- HYDROCHLORTHIAZIDE,
CHLORTHIAZIDE, BENZTHIAZIDE, POLYTHIAZIDE,
THIAZIDE like-CHLORTHALIDONE, METOLAZONE
INDAPAMIDE, ZIPAMIDE

3. C) Those acting on collecting ducts and tubules
AMILORIDE, TRIAMTERINE
Aldosterone antagonist- SPIRONOLACTONE,
EPLERENONE
INDIRECTLY ACTING
Osmotic diuretics- MANNITOL, GLYCEROL
Carbonic anhydrase inhibitors- ACETAZOLAMIDE,
DORZOLAMIDE, ETHOXZOLAMIDE,
METHAZOLAMIDE, DICHLORPHENAMIDE

4. 70%
20%
5%
4.5%
0.5%
Volume 1.5 L/day
Urine Na 100 mEq/L
Na Excretion 155 mEq/day
100%
GFR 180 L/day
Plasma Na 145 mEq/L
Filtered Load 26,100 mEq/day
Collecting
duct
Thick
Ascending
Limb

6.  Ethacrynic acid-ototoxicity, hepatotoxicity,
hypochloremic alkalosis
 Furosemide
 Bumetanide – 40 times potent
 Torsemide – three times potent and long acting
 Indacrinone –gout patients

8. RENAL TUBULAR
INTERSTITIUM LUMEN
Na+
K+
Cl-
TPC
Na+
H+
Na+
K+
PARACELLULAR DIFFUSION
Na+ K+
Mg++ Ca++
Cl-
+8 mV

9. RENAL TUBULAR
INTERSTITIUM LUMEN
Na+
K+
Cl-
TPC
Na+
H+
Na+
K+
PARACELLULAR DIFFUSION
Na+ K+
Mg++ Ca++
Cl-
+8 mV
THICK ASCENDING LOOP
LOOP DIURETICS

10.  Edematous conditions associated with CCF,
 Cirrhosis of liver, renal disease including nephrotic
syndrome
 Hypertension
 Acute renal failure
 Toxicity of ions
 Mild hyperkalemia
Non-diuretic use-moderate hypercalcaemia

11. Hyperuricemia
Hypercalciurea and hypomagnesaemia
Hypokalemia
Ototoxicity
Hyperglycemia
Hypersensitivity reactions
RESISTANCE TO LOOP DIURETICS
Renal insufficiency
Nephrotic syndrome
Cirrhosis of liver
Congestive heart failure

12.  Digitalis toxicity—due to hypokalemia
 Elevated serum lithium levels
 Aminoglycosides – increased ototoxicity
 NSAIDs diminish the action
 Probenacid competitive inhibition
 Cotrimoxazole –thrombocytopenia

13. MECHANISM OF ACTION
Inhibit Na+ and Cl- transporter in distal convoluted
tubules
Increased Na+ and Cl- excretion
Weak inhibitors of carbonic anhydrase, increased
HCO3- excretion
Increased K+/mg2+ excretion
Decrease Ca2+ excretion

14.  Early DCT
 Late DCT
Na+
Cl-
LUMEN
K+
Na+
Cl-
THIAZIDES

15.  Hypertension
 Congestive heart failure
 Hypercalciurea: prevent excess ca2+ excretion to
form stones in ducts
 Osteoporosis
 Nephrogenic diabetes insipidus
 Treatment of li+ toxicity

16.  Hypokalemia—digitalis toxicity
 Hyponatremia, hyperglycemia
 Hypochloremic alkalosis
 Diminished insulin secretion
 Elevated plasma lipids, hyperuricemia
 Hypercalcaemia
 Hypersensitivity reactions-sulfonamide derivative

17.  Spironolactone is a steroid compound, which is a
competitive aldosterone antagonist.
 It increases Na+ excretion and decreases K+ and
urea excretion. Its diuretic action is weak and is
achieved slowly.

18. Prevent K loss caused by other
diuretics in: Hypertension
Refractory edema
Primary aldosteronism- caused
by increased production of
aldosterone
Hirsutism due to P C O D.
Cirrhotic Edema

19. Collecting Duct
Na Na
Na
Na
Amiloride and Triamterene directly
block the ENaC channel(Epithelial
sodium channels)
Aldo
Spares potassium by decreasing the
lumen-negative gradient that drives
the expulsion of K/H into the lumen
Site of action: cortical collecting duct
Mechanism: Blocks E Na channels
Pharmacokinetics: Half-life = 3-5 hours
KK

20. Collecting Duct
Li
Li
Li
Li
Li
Amiloride blocks Li+ resorption
through Na+ Channelsreduces
lithium induced polyuria
They can be used to treat
edematous conditions including
liver cirrhosis, as they cause
hyperkalemia
Combined with thiazides to treat
refractory oedema

21.  Hyperkalemia-better to avoid K+ supplementation
 Drug interaction - do not use their combination,
since the potassium sparing effect is greater than
additive
 Caution with ACE inhibitors
 Reversible azotemia (triamterine)
 Triamterene nephrolithiasis.

22. Acetazolamide
prototype carbonic anhydrase inhibitor
developed from sulfanilamide (causes metabolic
acidosis and alkaline urine)
limited uses as diuretic
It is well absorbed orally and excreted unchanged in
urine
Action lasts for 8-12hrs

23. 1
1
1
1
1
1
1
1
1
1
1
1
1

24. inhibits carbonic anhydrase in
renal proximal tubule cells
carbonic anhydrase catalyzes
formation of HCO3- and H+ from
H2O and CO2
inhibition of carbonic anhydrase
decreases [H+] in tubule lumen
less H+ for Na+/H+ exchange
increased lumen Na+, increased
H2O retention

25.  Used to treat chronic open-angle glaucoma
aqueous humor has high [HCO3-]
 Acute mountain sickness  decrease CSF formation
and by decreasing pH
 Metabolic alkalosis they can produce
hyperchloremic acidosis
 Sometimes in epilepsy decreasing the pH
 Mostly used in combination with other diuretics in
resistant patients
 Alkalinisation of urine

26. Rapid tolerance
Increased HCO3- excretion causes metabolic acidosis
Drowsiness, fatigue, CNS depression
Paresthesia (pins and needles under skin)
Nephrolithiasis (renal stones), K+ wasting

27. Mannitol (prototype), Glycerol,
Mannitol is a nonelectrolyte of low molecular weight and is
pharmacologically inert freely filtered at glomerulus
Do not interact with receptors or directly block renal transport
activity dependent on development of osmotic pressure
Osmotic diuretics are not reabsorbed
Increases osmotic pressure specifically in the proximal tubule
and loop of Henle expands Extracellular volume
Inhibits transport processes in thick ascending LH
Prevents passive reabsorption of H2o
It increases urinary volume, excretion of all cations(Na, K,Mg,
Ca) and anions(Cl, HCO3, PO4)

28. Uses
To treat oliguria state in shock
Cerebral edema and glaucoma
To maintain GFR and urine flow in acute renal failure
Adverse effects
 Osmotic diarrhea- mannitol
 May worsen cardiac failure and pulmonary edema
C/I- acute tubular necrosis, anuria, pulmonary edema, CHF,
cerebral hemorrhage, left ventricular failure

29. Loop diuretics can be used to treat mild to moderate
hypercalcaemia
Thiazides reduce volume of urine in diabetes
insipidus more water reabsorption from collecting
ducts
Thiazides are helpful in idiopathic hypercalciurea
Potassium sparing diuretics can reduce lithium induced
polyuria
Amiloride can be used to treat cystic fibrosis by
increasing the fluidity in respiratory secretions

30. Spironolactone in congestive heart failure retards the
disease progression and reduces mortality
Carbonic anhydrase inhibitors and osmotic diuretics in
glaucoma
Osmotic diuretic in cerebral oedema
CAs can be used in metabolic alkalosis-as they produce
hyperchloremic acidosis
CAs can be used to treat petitmal epilepsy
Acute mountain sickness

31. Download slides from
Authorstream-raghuprasada
Slideshare-raghuprasada
Youtube-raghuprasada