Loop diuretics such as furosemide act directly on the ascending loop of Henle to increase urinary output and reduce fluid volume and blood pressure. Thiazide diuretics such as hydrochlorothiazide act on the distal convoluted tubule to inhibit sodium reabsorption and increase the excretion of sodium, chloride, water and potassium. Potassium-sparing diuretics such as spironolactone competitively bind to aldosterone receptors to prevent potassium loss while sodium and water are excreted. Osmotic diuretics such as mannitol work by increasing the osmolarity of the renal filtrate to pull water from tissues into the renal tubules.

1. Drugs affecting
Renal system
Diuretics

2. Structure of KIDNEY
 Functional unit : Nephron
 Glomerulus, Proximal convoluted tubule,
Loop of Henle, Distal convoluted tubule,
Collecting tubules and ducts.

4. Normal kidney function
Excretion of drugs, drug metabolites &
waste products such as
Urea
Uric acid
Creatinine
Regulation of NaCl and electrolyte content
(aldosterone, natriuretic peptides)

5.  Regulation of water balance (ADH)
 Acid-base balance
 Local hormone synthesis : Angiotensin,
prostacyclin & erythropoeitin.
 Hydroxylation of Vitamin D

6. Mechanisms of urine formation
 Glomerular filtration
 Tubular Reabsorption
 Active tubular secretion

7. Renal tubule transport
mechanisms

9. DIURETICS
Definition :
Drugs that cause excretion of sodium
and water in urine.

10. Classification
High efficacy Medium efficacy Low efficacy
Loop diuretics
Furosemide
Bumetanide
Torasemide
Osmotic
diuretics
Mannitol
Isosorbide
Glycerol
Thiazides
Hydrochlorthiazide
Benzthiazide
Hydroflumethiazide
Bendroflumethiazide
Thiazide like
Chlorthalidone
Metolazone
Xipamide
Indapamide
Clopamide
CA inhibitors
Acetazolamide
dorzolamide
brinzolamide
K+ sparing diuretics:
Aldosterone
antagonists
Spironolactone
Eplerenone
Renal epithelial Na+
channel inhibitors
Triamterene
Amiloride

15. Diuretic agents
 Diuresis : increase in urine volume
 Natriuresis : increase in sodium
excretion
 Directly act on cells of nephron or
indirectly modify content of filtrate

16. Classification
 Act directly on different segments of
nephron
 Act indirectly by modifying content of
urinary filtrate
 Weak diuretics mainly have nondiuretic
use

17. Different segments of nephron
 Thick ascending loop of Henle :
o Furosemide
o Bumetanide
o Torsemide
o Piretanide
o Ethacryanic acid
o Indacrinone

18. Early part of DCT :
 Thiazide group
o Hydrochlorthiazide
o Chlorothiazide
o Benzthiazide
o Polythiazide
o Bendroflumethiazide
o Clopamide

19.  Thiazide like diuretics :
o Chlorthalidone
o Xipamide
o Indapamide
o Metolazone
o Quinethazone

20.  Collecting tubules & ducts :
o Amiloride
o Triamterene

21.  Later part of DCT & Collecting tubules :
o Spironolactone
o Eplerenone

22. Modifying urinary filtrate
 Osmotic diuretics :
o Mannitol
o Glycerol

23. Weak diuretics
 Carbonic anhydrase inhibitors :
o Acetazolamide
o Dorzolamide
o Brinzolamide
o Methazolamide
o Ethoxzolamide
o Dichlorphenamide

24. Loop diuretics

26. Loop Diuretics
 Act directly on the ascending limb of the
loop of Henle to inhibit sodium & chloride
reabsorption
 Increase renal prostaglandins, resulting in
the dilation of blood vessels and reduced
peripheral vascular resistance

27. Drug Effects
 Potent diuresis and subsequent loss of
fluid
 Decreased fluid volume causes:
 Reduced BP
 Reduced pulmonary & systemic vascular
resistance
 Reduced central venous pressure
 Reduced left ventricular end-diastolic
pressure
 Potassium and sodium depletion

28. Indications
 Diuretic uses :
o Edema associated with CHF, Cirrhosis
or renal disease
o Control of hypertension esp associated
with renal disease
o Oliguric renal failure
o Toxic anions Br, I, F ingestion
o Mild hyperkalemia

29.  Non diuretic uses :
o Mild-moderate hypercalcemia

30. Adverse effects
o Hyperuricemia
o Hypercalciuria & hypomagnesaemia
o Hypokalemia with met alkolosis
o Ototoxicity
o Hyperglycemia
o Hypersensitivity reaction
o GI disturbance, hepatotoxic, pancreatitis
with ethacrynic acid
o Myalgia with bumetanide & piretanide.

31. Drug Interactions
 Digitalis
 Lithium
 NSAIDs
 Probenacid
 Cotrimoxazole
 Aminoglycosides

32. Thiazides

34. Thiazides
 Acts on the distal convoluted tubule
 Inhibit tubular reabsorption of sodium,
chloride, and potassium ions
 Result: water, sodium, and chloride are
excreted
 Potassium is also excreted to a significant extent

35. Indication
 Diuretic uses :
 Essential Hypertension – first line drug
 Edematous states :
pulmonary edema due to CCF, nephrotic
syndrome & pregnancy

36.  Non diuretic uses :
 Diabetic insipidus
 Idiopathic hypercalciuria

37. Adverse Effects
 Hypokalemia
 Hypochloraemic alkolosis
 Hyperuricaemia
 Hypercalcemia
 Hyperglycemia
 Hyperlipidaemia
 Erectile dysfunction
 Hypersensitivity reaction

38. Drug interaction
 Digitalis
 Lithium
 NSAIDs
 Probenacid
 Cotrimoxazole
 Aminoglycosides

39. Potassium-Sparing
Diuretics

41. Mechanism of Action
 Interfere with sodium-potassium exchange
in collecting ducts and convoluted tubules
 Prevent potassium from being pumped into
the tubule, thus preventing its secretion

42.  Competitively bind to aldosterone
receptors
 Block the reabsorption of sodium and
water
 Sodium and water are excreted

43. Uses of Amiloride
 Diuretic
 Edematous –Liver cirrhosis
 Combined with thiazides in refractory edema
 Combined with thiazide and loop diuretics in
hypertension
o Amiloride-5-10mg / d
o Triamterene-50-100mg / d

44.  Non diuretic use:
 Prevents lithium induced polyuria
 Cystic fibrosis
 Potassium loss

45. Adverse effects
 Hyperkalaemia
 Triamterene-increases blood urea,
nausea, dizziness & precipitates renal
stones
 Amiloride -fall in BP , diarrhoea , skin
rashes

46. Drug interactions
 Potassium supplements & ACE inhibitors
 NSAIDS decrease effects of these agents
 Quinidine increase risk of arrhythmias

47. Aldosterone receptor
antagonist

48. Indications
 Diuretic use :
 Primary and secondary
hyperaldosteronism
 With loop and thiazide diuretics in
hypertension

49.  Non diuretic uses:
 CHF
 Hypokalaemia.

50. Adverse effects
 Hyperkalaemia
 Delays healing of peptic ulcer
 GIT disturbances, skin rashes,
gynaecomastia, menstrual irregularities

51. Osmotic Diuretics

52. Osmotic diuretics
 Act by modifying the content of urinary
filtrate
 Cause increase osmolarity

53. Mechanism of Action
 Work mostly in the proximal tubule
 Nonabsorbable, producing an osmotic
effect
 Pull water into renal tubules from the
surrounding tissues

54.  Inhibits tubular reabsorption of water and
solutes
 Increases glomerular filtration and renal
plasma
 Reduces excessive intraocular pressure

55. Indications
 Used in the treatment of patients in the
early oliguric phase of ARF
 To promote the excretion of toxic
substances
 Reduction of intracranial pressure
 Treatment of cerebral edema

56. Adverse Effects
 Convulsions
 Thrombophlebitis
 Pulmonary congestion
 Osmotic diarrhoea
 Headaches, chest pains, tachycardia
 Blurred vision
 Chills and fever

57. Carbonic Anhydrase
Inhibitors

59. Carbonic anhydrase inhibitors
 Acetazolamide is prototype drug

60. Mechanism of Action
 Carbonic anhydrase helps to make H+ ions
available for exchange with sodium and water in
the proximal tubules
 CAIs
 block the action of carbonic anhydrase
 thus preventing the exchange of H+ ions with
sodium and water
 reduces H+ ion concentration in renal tubules

61.  Result:
 increased excretion of bicarbonate, sodium,
water, & K+
 Reabsorption of water is decreased and urine
volume is increased

62. Indications
 Adjunct drugs in the long-term
management of open-angle glaucoma*
 Used with miotics to lower intraocular
pressure before ocular surgery in certain
cases
 Also useful in the treatment of:
 Edema
 Epilepsy
 High-altitude mountain sickness

63.  Acetazolamide is used in the management
of edema secondary to HF when other
diuretics are not effective*
 Urinary alkalinization : urate caliculi &
cystinuria
 Metabolic alkalosis
 Recently : reducing respiratory work in
patient weaned from respirator

64.  CAIs are less potent diuretics than loop
diuretics or thiazides — the metabolic
acidosis they induce reduces their diuretic
effect in 2-4 days

65. Adverse effects
 Refractoriness after repeated use
 Hyperchloraemic acidosis
 Drowsiness, paraesthesia
 Hypokalaemia

66. Miscellaneous Diuretics
 Xanthine derivatives are naturally
occurring drugs that produce mild diuretic
responses.
(caffeine, theobromine, theophylline)
 They stimulate urine flow by increasing
blood flow to kidneys.

67.  Side effects
 CNS stimulation, hypotension, and
headache.

68. Anti-Diuretics

69. Anti-Diuretics
 Agents that decrease urine volume
 Primarly indicated in treatment of Diabetic
insipidus.

70. Antidiuretic agents
 ADH & its analogues :
o Desmopressin
o Terlipressin
o Felypressin
o Lypressin

71. Antidiuretic agents
 Thiazides
 Chlorpropamide, Clofibrates,
Carbamazepines.
 Amilorides.

72. Antidiuretic hormone (ADH)
 Also known as arginine vasopressin
 Hypothalamus & posterior pituitary
 Increased plasma osmolality or decreased
volume of ECF.
 Acts on V1a V1b V2.

73. Actions of ADH
 Water permeabilty in CD : V2
 Potent pressor of blood vesels V1a & also
vasodilation through V2
 Release of vWF & Factor Viii from
endothelium
 ACTH release : V1b

74. ADH receptors
Characteristics Vasopressin receptors
V 1a V 1b V2
Location Vascular & smooth muscles Anterior pituitary Collecting duct
Platelets Endothelium
Hepatocytes
Function Vasoconstriction ACTH release Antidiuretic
Visceral smooth contraction
Platelet aggregation &
glycogenolysis
Mechanism PLC / IP3-DAG PLC / IP3-DAG Adenyl cyclase

75. Therapeutic uses
 Based on V1 receptor actions :
o Bleeding esophageal varices
o Postop paralytic ileus & drive out intestinal
gas before abdominal radiography
o Abdominal surgery & Portal hypertension
o Acute hemorrhagic gastritis

76.  Based on V2 receptor actions :
o Central Diabetes insipidus
o Primary nocturnal enuresis
o Post lumbar puncture headache
o Hemophilia A & von Willebrands disease

77. Adverse effects
 Based on V1 receptor actions :
o Facial pallor
o Nausea
o Abdominal cramps
o Urge to defecate
o Precipitate angina

78. Adverse effects
 Based on V2 receptor actions :
o Fluid retention
o Hyponatremia

79. Adverse effects
 Common to Vasopressin & Desmopressin
o Intranasal : irritation, ulceration, rhinitis
o Rare : Urticaria, pruritis, other allergy.

80. ADH receptor antagonist
 V1 receptor antagonist :
 Relcovaptans
o CHF
o Hypertension

81.  V2 receptor antagonist :
 tolvaptans
 lixivaptans
 satavaptans
 mozavaptans
o Treatment of SIADH

82.  Antagonist at V1A / V2
 Conivaptans :
o SIADH
o CHF
 By iv route

83. Adverse effects
 Postural hypotension
 Hypokalemia
 Polydipsia
 Polyuria