This PPT covers drugs used as diuretics. Pharmacotherapy of all drugs used as diuretics are covered here. Thiazides, high ceiling, aldosterone antagonist, osmotic diuretics are explained

1. DIURETICS
PREPARED BY: JEGAN. S. NADAR

2. DIURETICS
 Diuretics are drugs that increase the volume of urine excreted
 Most diuretic agents are inhibitors of renal ion transporters that decrease the
reabsorption of Na+ at different sites in the nephron.
 As a result, Na+ and other ions, such as Cl−, enter the urine in greater than normal
amounts along with water, which is carried passively to maintain osmotic equilibrium.
 Diuretics, thus, increase the volume of urine and often change its pH, as well as the ionic
composition of the urine and blood
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5. HIGH EFFICACY DIURETICS / LOOP DIURETICS
 They are Inhibitors of Na+ K+ 2Cl¯ Co-transport
 They act major mainly on the ascending limb of the loop of Henle
 Of all the diuretics, these drugs have the highest efficacy in mobilizing Na+ and Cl− from
the body.
 They produce more amounts of urine as compared to other diuretics.
 Furosemide is the most commonly used of these drugs
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6. MECHANISM OF ACTION
 Loop diuretics inhibit the co-transport of Na+ K+ 2Cl− in the luminal membrane in the
ascending limb of the loop of Henle
 This causes decreased reabsorption of these ions
 Urine volume increases
 These agents have the greatest diuretic effect of all the diuretic drugs, since the ascending
limb accounts for reabsorption of 25% to 30% of filtered NaCl
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8. PHARMACOKINETICS:
 Loop diuretics are administered orally or parenterally.
 Their duration of action is relatively brief (2 to 4 hours)
 They are secreted into urine.
SIDE EFFECTS
 Ototoxicity
 Hyperuricemia
 Acute hypovolemia
 Hypokalemia Jegan

9. USE OF HIGH CEILING DIURETICS
1. Edema
2. Acute pulmonary edema
3.Cerebral edema
4. Hypertension
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10. MEDIUM EFFICACY DIURETICS / THIAZIDE DIURETICS
 They are Inhibitors of Na+Cl¯ symport
 The thiazides are the most widely used diuretics.
 They are sulfonamide derivatives.
 All thiazides affect the distal convoluted tubule, and all have equal maximum diuretic
effects
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11. MECHANISM OF ACTION
 The thiazide and thiazide-like diuretics act mainly in the cortical region of the ascending
loop of Henle and the distal convoluted tubule
 They Inhibit Na+Cl¯ symport present in the tubules
 Therefore, reabsorption of these ions is decreased.
 As a result, these drugs increase the concentration of Na+ and Cl− in the tubular fluid
 Decreased sodium reabsorption causes increase in blood volume
 They have a lesser effect in the proximal tubule.
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13. PHARMACOKINETICS:
 The drugs are effective orally.
 Most thiazides take 1 to 3 weeks to produce a stable reduction in blood pressure
 They exhibit a prolonged half-life.
 All thiazides are secreted by the organic acid secretory system of the kidney
SIDE EFFECTS
• Hypokalaemia – muscle pain and fatigue
• Hyperglycemia: Inhibition of insulin release due to K+ depletion (proinsulin to insulin) –
precipitation of diabetes
• Hyperlipidemia: rise in total LDL level – risk of stroke
• Hyperurecaemia: inhibition of urate excretion
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14. USE OF THIAZIDE DIURETICS
1. Edema
2. Hypertension
3.Heart failure
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15. POTASSIUM-SPARING DIURETICS
 Potassium-sparing diuretics act in the collecting tubule to inhibit Na+ reabsorption and
K+ excretion
 The major use of potassium sparing agents is in the treatment of hypertension (most
often in combination with a thiazide) and in heart failure (aldosterone antagonists).
 These drugs should be avoided in patients with renal dysfunction because of the
increased risk of hyperkalemia.
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16. SPIRONOLACTONE
SPIRONOLACTONE
 It is a steroid, chemically related to the mineralocorticoid aldosterone.
 Aldosterone penetrates the late DT and CD cells and acts by combining with an intracellular
mineralocorticoid receptor (MR)
 By combing with receptor aldosterone induces the formation of ‘aldosterone-induced proteins’ (AIPs).
 The AIPs promote Na+ reabsorption and K+ secretion.
 Spironolactone acts from the interstitial side of the tubular cell, combines with MR and inhibits the
formation of AIPs in a competitive manner
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18. PHARMACOKINETICS
 Spironolactone is absorbed after oral administration and are significantly bound to
plasma proteins.
 Spironolactone is extensively metabolized and converted to several active metabolites.
 The metabolites, along with the parent drug, are responsible for the therapeutic effects
USE
 Diuretic
 Secondary hyperaldosteronism
 Heart failure
 Resistant hypertension
 Ascites
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19. ADVERSE EFFECTS
Spironolactone can cause
 Gastric upset.
 Gynecomastia in male patients
 Menstrual irregularities in female patients.
 Hyperkalemia,
 Nausea,
 Mental confusion can occur.
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20. TRIAMTERENE AND AMILORIDE
 Triamterene and amiloride block Na+ transport channels
 This results in decrease in Na+/K+ exchange.
 Causes sodium excretion and prevents potassium secretion
 Like the aldosterone antagonists, these agents are not very efficacious diuretics.
 Both triamterene and amiloride are commonly used in combination with other diuretics,
usually for their potassium sparing properties.
 The side effects of triamterene include increased uric acid, renal stones, and K+
retention Jegan

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22. CARBONIC ANHYDRASE INHIBITOR
ACETAZOLAMIDE
 Carbonic anhydrase catalyzes the reaction of CO2 andH2O, leading to H2CO3, which
spontaneously ionizes to H+ and HCO3 (bicarbonate).
 Acetazolamide inhibits carbonic anhydrase located intracellularly (cytoplasm) and on
the apical membrane of the proximal tubular epithelium
 Acetazolamide will inhibit carbonic anhydrase because of which the decreased level of
H+ decreases which impairs Na + exchange since Na/H+ pump will not function
 Sodium excreted and diuresis occurs
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24. PHARMACOKINETICS:
 Acetazolamide can be administered orally or intravenously.
 It is approximately 90% protein bound
ADVERSE EFFECTS:
 Metabolic acidosis (mild),
 potassium depletion,
 renal stone formation,
 drowsiness,
THERAPEUTIC USES:
 Glaucoma
 Mountain sickness
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25. OSMOTIC DIURETICS
 Mannitol is a nonelectrolyte of low molecular weight that is pharmacologically inert—
 It can be given in large quantities sufficient to raise osmolarity of plasma and tubular
fluid.
 It is minimally metabolized in the body; freely filtered at the glomerulus and undergoes
limited reabsorption:
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26. Mannitol appears to limit tubular water and electrolyte reabsorption in a variety of ways:
 Retains water isoosmotically in PT—dilutes luminal fluid which opposes NaCl
reabsorption.
 Inhibits transport processes in the thick AscLH by an unknown mechanism
 Expands extracellular fluid volume (because it does not enter cells, mannitol draws water
from the intracellular compartment)
 Passive salt reabsorption is reduced.
Jegan

27. Thank You