Diuretics are drugs that promote increased production of urine. The main classes of diuretics are loop diuretics, thiazide diuretics, carbonic anhydrase inhibitors, osmotic diuretics, and aldosterone antagonists. Loop diuretics such as furosemide act on the loop of Henle and are highly effective. Thiazide diuretics such as hydrochlorothiazide are commonly used to treat hypertension and edema. Carbonic anhydrase inhibitors reduce fluid production in various tissues. Osmotic diuretics work by increasing osmotic pressure in the kidney tubules. Aldosterone antagonists such as spironolactone counteract sodium retention caused by

1. DIURETICS

3. The Nephron
• Nephrons are the structural and functional units that form
urine, consisting of:
– Glomerulus-a tuft of capillaries associated with a renal
tubule
– Bowman’s capsule-blind, cup-shaped end of a renal tubule
that completely surrounds the glomerulus
– Long tubular portion

4. STRUCTURE OF GLOMERULI

5. Anatomy of the Bowman’s Capsule
• Parietal layer
• Visceral layer - Podocytes

6. Juxtaglomerular Apparatus (JGA) and
macula densa

7. Mechanisms of Urine Formation
 Urine formation and
adjustment of blood
composition involves
three major processes
 Glomerular filtration
 Tubular reabsorption
 secretion

8. Mechanisms of Urine Formation
• The kidneys filter the body’s entire plasma volume 60 times
each day
• Gfr is 180 L/day and plasma vol is 3L so its 60 times each
day……
• The filtrate:
– Contains all plasma components except protein

9. PCT
• Reabsorption of 65% of filtered
Na+/ K+/ CA2+, and Mg2+ , 85% of
NaHCO3
•100% of glucose and amino
acids.
•Isotonic reabsorption of water.
•CARBONIC ANHYDRASE
INHIBITORS

10. Contd.
• Specific sodium-coupled symporters→ reabsorption
of glucose, amino acids, phosphate, and sulfate from
the glomerular filtrate.
• The proximal tubule → secretion and reabsorption of
organic weak acids and weak bases
• Basolateral K+ channels maintain an inside-negative
membrane potential

12. LOOP OF HENLE
Active reabsorption of 15–25% of filtered Na+/ K+/ Cl–
Secondary reabsorption of Ca2+ and Mg2+
Tubular fluid emerging from the ascending thin limb is hypertonic
 LOOP DIURETICS

13. • 4 times higher osmolarity of medullary tip
(papilla) is maintained by the hairpin structure
of the loop of Henle acting as passive counter
current multiplier and the arrangement of
blood vessels as vasa recta

14. DCT
•SEGMENT IS IMPERMEABLE TO WATER
•Active reabsorption of 4–8% of filtered
Na+ and Cl–
• Ca2+ absorption under parathyroid
hormone control
•NO LEAKY K+ CHANEL
•THIAZIDES

15. CORTICAL CT
• Na+ alone pump
• Na+ reabsorption (2–5%) K+
and H+ secretion by
aldosterone
• K+-sparing diuretics,amiloride

16. MEDULLARY CT
•Water reabsorption under vasopressin
control
•NO Na+K+ATPase on basolateral
membrane

17. FREE WATER CLEARANCE
• the rate of free-water clearance represents the rate at which
solute-free water is excreted by the kidneys
• When free-water clearance is positive, excess water is being
excreted by the kidneys
• when free-water clearance is negative, excess solutes are
being removed from the blood by the kidneys and water is
being conserved.

19. Classification
High efficacy diuretics (Na+ - K+ -2Cl-
cotransport inhibitor):
• Sulfomyl Derivatives:Furosemide, Bumetanide,
Torsemide,
 Medium efficacy diuretics (lnhibitors of Na--
Cl- sympoft)
(a) Benzothiadiazines (thiazides)
• Hydrochlorothiazide, Benzthiazide,
• Hydroflumethiazide, Bendrofumethiazide

20. Contd.
(b)Thiazide like (related heterocyclics)
• Chlorthalidone, Metolazone,
Xipamide,Indapamide,Clopamide
Weak or adjunctive diuretics:
(a) Carbonic anhydrase inhibitors:Acetazolamide
(b) Potassium sparing diuretics
(l) Aldosterone antagonist:
• Spironolactone, Eplerenone
(li) Inhibitors of renal epithelial Na+ channel
• Triamterene, Amiloride.

21. Contd.
(c) Osmotic diuretics
• Mannitol, Isosorbide, Glycerol

22. •Loop diuretics

24. Actions
• Decrease Positive and negative water clearance
• Increase renal blood flow due to prostaglandin
• Don’t decrease GFR by activating TGF
• Increase calcium excretion
• All inhibitors of Na+-K+-2Cl– symport increase urinary
K+ and titratable acid excretion
• Carbonic anhydrase inhibition
• Uric acid secretion

25. Uses
• Acute pulmanory edema (Acute LVF following
MI )
– Intravenous administration of furosemide or its
congeners produces prompt relief
– due to vasodilator action
• Edema
– cardiac,
– hepatic
– renal

26. Contd.
• Cerebral edema
– Furosemide combined with osmotic diuretics to
improve efficacy
• Hypertension: only in presence of renal
insufficiency, CHF, or in resistant case of
hypertensive emergencies

27. Contd.
• Along with BT:
to prevent volume overload
• Hypercalcemia of malignancy:
Promotes Ca excretion and prevent volume
overload

28. Pharmakokinetics
DRUG RELATIVE
POTENCY
ORAL
BIOAVAILABILIT
Y
t ½ hr.
Furosemide 1 60% 1.5
Bumetanide 40 80% 0.8
Ethacrynic acid 0.7 100% 1
Torsemide 3 80% 3.5

29. • Thiazide diuretics

30. Mechanism of action

31. Actions
• Decrease positive water clearance
• Carbonic anhydrase inhibition
• Reduce GFR
• Decrease calcium excretion

32. Uses
1. Hypertension
• Once daily dose is sufficent
• No fluid retention
• Low incidence of postural hypotension
• Effective in isolated systolic hypertension
• Low cost
• Lesser incidence of hip fracture because of
hypocalciuric action

33. Contd.
2. Edema:
• Mild to moderate
• For maintenance therapy
3. Hypercalciura
4. Diabetes insipidus:
• Reduce GFR
• Induce a sustained electrolyte depletion so
glomerular filtrate is completely reabsorb
Isotonicallly in PT

34. • Adverse effects

35. LOOP/THIAZIDE DIURETICS
• Hypokalemia
• Dilutional hyponatremia
• GIT & CNS disturbances
• Hyperuricemia
• Hyeperglycemia & hyperlipidemia
• Hypomagnesemia
• Hypo/hypercalcemia

36. CONTD.
• Ototoxicity
• Allergic reaction: rashes, photosensitivity
• Thiazides aggravates renal insufficiency,
probably by reducing g.f.r.

37. Contd.
• Diuresis induced in cirrhotics may precipitate
mental disturbances and hepatic coma.
• Avoided in toxaemia of
Pregnancy:miscarriage,fetal death

38. Interactions-Loop/thiazide diuretics
(1) aminoglycosides (synergism of ototoxicity
caused by both drugs)
(2) anticoagulants (increased anticoagulant
activity)
(3) digitalis glycosides (increased digitalis-induce
arrhythmia)
(4) lithium (increased plasma levels of lithium
(5) propranolol (increased plasma levels of
propranolol)

39. Contd.
(6) sulfonylureas (hyperglycemia)
(7) cisplatin (increased risk of diuretic-induced
ototoxicity)
8) NSAIDs (blunted diuretic response and salicylate
toxicity when given with high doses of salicylates)
(9) probenecid (blunted diuretic response) .

40. • Carbonic Anhydrase inhibitors

41. Contd.
• Acetazolamide
• Dorzolemide
• Brinzolamide

42. Mechanism of actions

43. Other action
Extrarenal actions of acetazolamide are:
• Lowering of intraocular tension due to
decreased formation of aqueous humour (it
is rich in HCO3-).
• Decreased gastric HCI and pancreatic
NaHCO3 secretion: This action requires
very high doses-clinically not significant

44. Contd.
• Raised level of CO2 in brain and lowering
of pH sedation and elevation of seizure
threshold.
• Alteration of CO2 transport in lungs and
tissues: these actions are masked by
compensatory mechanisms.

45. Uses
• Glaucoma:
Brinzolamide and Dorzolamide topically used
• To alkalization of urine
For UTI and excretion of some acidic drug
• Epilepsy
As adjuvant in absence seizures

46. Contd.
• Acute mountain sickness
Reduce CSF formation and lowers brain pH
• Periodic paralysis

47. Adverse Effect
• Hypokalemia
• Metabolic acidosis
• Hypersensitivity reaction
• Calculus ,ureteric colic
• Bone marrow depression
• Hepatic coma precipitated

48. • Osmotic Diuretics

49. Mechanism of Action
• Retains water isoosmotically in PT Dilute luminal
fluid which opposes NACl reabsorption
• Inhibit transport process in thick ASCLH
• Expand the extracellular fluid volume:increases g.f.r.
and inhibits renin release
• Increases renal blood flow, especially to the medulla—
medullary hypertonicity is reduced -Corticomedullary
osmotic gradient is dissipated—passive salt
reabsorption is reduced

50. Contd.
Administration
• Mannitol can not absorb orally
• Given 10-20% i.v. solution

51. Use
 Increased intracranial & intraocular tension:
• Head injury
• Stroke
• Acute congestive glaucoma
 To maitain gfr & urine flow in impending acute renal
failure
• Shock
• Severe trauma
• Cardiac surgery
• Hemolytic reactions

52. Contd.
• Dialysis dysequlibrium syndrome
– To counteract low osmolality of plasma/e.c.f.
due to rapid haemodialysis or peritoneal dialysis

53. Adverse effects
• Headche
• Nausea and vomiting
• Hypersensitivity reaction

54. Contraindications
• Acute tubular necrosis
• Anuria
• Pulmonary edema
• Acute LVF
• Cerebral haemorrhage

55. • Aldosterone antagonist

56. Drugs
• Spironolactone, Eplerenone

58. Uses
• Congestive heart failure
– As additional drug to conventional therapy in
moderate to severe CHF
– Prevents ventricular remodeling & mortality

59. Other uses
• To counteract K+ loss due to Thiazide and Loop
diuretics
• Edema:
Mostly in Cirrhotic and Nephrotic edema where
Aldosterone level is high
• Hypertension:
a. Use as adjuvant therapy
b. Attenuate hypertension related Renal fibrosis
and vascular /ventricular hypertrophy

60. Contd.
• Hyperaldosteronism---primary
---secondary

61. Adverse Effect
• Drowsiness, Ataxia, loose motions
• Gynecomastia, Erectile dysfunction, breast
tenderness and menstrual irregularities
• Hyperkalemia
• Acidosis
• Peptic ulcer aggravated

62. Pharmacokinetics
• Oral bioavailability of spironolactone from
microfine powder tablet is 75%
• Completely metabolized in liver
• Converted to active metabolites, the most
important of which is Canrenone

63. Interactions
• Hyperkalemia-ACE –I ,ARB
• Aspirin block spironolactone action (inhibit
tubular secretion of canrenone)
• Spironolactone increase digoxin conc.

64. • Inhibitors of renal epithelial
Na+ channel

65. Drugs
• Amiloreide
• Traimterene

67. Uses
• Lithium induced DI
• Cystic fibrosis
• Hypokalemia

68. Adverse effect
• GIT side effects
• Hyperkalemia
• Rise in blood urea
• Impaired glucose tolerance
• Photosensitivity reactions

69. • Thiazides diuretics causes all EXCEPT:
• (a) Hyperglycemia
• (b) Increased calcium excretion
• (c ) Useful in congestive heart failure
• (d) Decreased uric acid excretion

70. • Regarding furosemide true statement is:
• (a) Acute pulmonary edema is an indication
• (b) Acts on PCT
• (c) Mild diuresis
• (d) Given only by parenteral route

71. • Spironolactone is contraindicated with which
of the following drugs?
• (a) Enalapril
• (b) Atenolol
• (c) Verapamil
• (d) Chlorthiazide

72. • Aldosterone antagonists are not useful in the
treatment
• of:
• (a) Hypertension
• (b) Congestive heart failure
• (c) Gynaecomastia
• (d) Hirsutism

73. • Intravenous furosemide is used for rapid control
of symptoms in acute left ventricular failure. It
provides quick relief of dyspnoea by:
• (a) Producing bronchodilation
• (b) Causing rapid diuresis and reducing circulating
• blood volume
• (c) Causing venodilation
• (d) Stimulating left ventricular contractility

74. • Which of the following diuretics can result in
metabolic acidosis?
• (a) Indapamide
• (b) Furosemide
• (c) Hydrochlorthiazide
• (d) Acetazolamide

75. • Epleronone is:
• (a) Aldosterone antagonist
• (b) Can cause hyperkalemia in predisposed
patients
• (c) A diuretic
• (d) All of these

76. • Loop diuretics acts on:
• (a) PCT
• (b) DCT
• (c) Thick ascending limb of loop of Henle
• (d) Collecting duct

77. • Furosemide causes all except:)
• (a) Hyperglycemia
• (b) Hypomagnesemia
• (c) Hypokalemia
• (d) Acidosis

78. •THANK YOU