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
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
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.
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