Pharmacology: Renal Pharmacology, Diuretics

1. DIURETICS
Dr. Ankita Bist
Assistant Professor
Department of Pharmacology

2. • 76 years old lady, has a history of cardiovascular disease including
hypertension and heart failure. She had been receiving furosemide
and developed mild hypokalemia for which a potassium
supplement was prescribed. 2 weeks later she arrives at the
hospital and during the assessment, she reveals she has been
experiencing nausea, abdominal cramping, and diarrhea along
with some muscle cramps, weakness, and a feeling that “her heart
was going to jump out of her chest.” What might be occurring
now?

4. DIURETICS
• Drugs which cause a net loss of Na+ and water in urine.
• Except osmotic diuretics which do not cause natriuresis
but produce diuresis
• Causes increase in urine volume.
• Causes concomitant decrease in extra-cellular volume
(blood volume)

5. CLASSIFICATION OF
DIURETICS
 Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide,
Metolazone
 High ceiling: Furosemide, Bumetanide, Torsemide,
 K+ sparing: Spironolactone, Eplerenone ,Triamterene,
Amiloride
 Others:
 Carbonic Anhydrase Inhibitors: Acetazolamide,
Methazolamide, Dorzolamide
 Osmotic Diuretics: Mannitol, Glycerin, Isosorbide

6. THIAZIDE DIURETICS
Mechanism of action:
•Inhibit Na+-Cl- symporter
•Increase excretion of Na and H2O causing decrease in blood
volume hypotensive action
•Na exchanges with K+ in the DT causing K+ loss: hypokalemia
•Additional Carbonic anhydrase inhibitory action
•Reduce Ca++ excretion: hypercalcemia
•Hyperglycemia
•Hyperuricemia

7. USES
• Hypertension (hydrochlorothiazide, indapamide)
• Edema
• Hypercalciuria and renal ca stones
• Diabetes insipidus (DI) (nephrogenic responds better)

8. LOOP
DIURETICS
Mechanism of action:
• Thick ascending limb of loop of Henle
• Inhibit Na+ K+-2Cl- cotransporter
• Increase excretion of Na, Cl and H2O causing decrease in blood
volume
• Na exchanges with K+ in the DT causing K+ loss: hypokalemia
• Increases Ca++ and Mg ++ excretion
• Hyperuricemia and hypokalemia

9. USES
• Edema: cardiac, hepatic, renal
• Acute pulmonary edema
• Cerebral edema – (osmotic diuretics more preferred)
• Hypertension (only in presence of CHF, renal insufficiency etc)
• Hypercalcemia

10. LOOP & THIAZIDE DRUGS:
COMPLICATIONS
• Hypokalemia
• Acute saline depletion
• Dilutional hyponatremia
• Hearing loss
• Hyperuricemia
• Hyperglycemia
• Hypocalcemia with loop and hypercalcemia with thiazides
• Magnesium loss

11. K+ SPARING DIURETICS
• MOA: competitive antagonists, either compete with aldosterone
or directly block Na channels.
• Aldosterone competitive antagonists: spironolactone, eplerenone
• Reduce reabsorption of Na+ and water
• K+ loss in urine is decreased
• Conserve K+ indirectly, produces mild natriuresis
• No effect in the absence of aldosterone
• Useful in states related to high aldosterone activity

12. ADVERSE EFFECTS
• Drowsiness, mental confusion, ataxia, epigastric discomfort, loose
motions
• Spironolactone has hormonal side effects: gynecomastia, erectile
dysfunction, menstrual irregularities
• Eplerenone is safer in this regard
• Hyperkaliemia in renal impaired patients, and those taking ACE I/
ARB’s
• Acidosis in cirrhotic
• Contraindicated in ulcer patients

13. RENAL EPITHELIAL NA+ CHANNEL
INHIBITORS
• Triamterene, amiloride
• Mechanism of action: blocks luminal renal epithelial Na+
channels, decrease reabsorption of Na+.
• Decreases K+ excretion, accompanied with small increase in Na+
loss, reduces Ca2+ and Mg2+ excretion
• Uses: hypertension, as adjuvant, prevents hypokalemia
• Adverse effects: nausea, diarrhea, headache, impaired glucose
tolerance, photosensitivity, rise in blood urea. HYPERKALEMIA

14. CARBONIC ANHYDRASE
INHIBITORS
• Acetazolamide, methazolamide, dorzolamide
• Reversible, non-competitive inhibitor of carbonic anhydrase.
• Acts at PT, DT and CD
• Less H+ available for exchange with Na+, induces natriuresis
• USES: Glaucoma, Alkalinize urine, epilepsy, mountain sickness
• ADR: Acidosis, hypokalemia, drowsiness, hypersensitivity, Hepatic
coma

15. OSMOTIC DIURETICS
• Mannitol, isosorbide
• Non-electrolyte, low molecular weight, pharmacologically inert
• Acts by:
raising osmolarity of plasma and tubular fluid
gets freely filtered at glomerulus
limits tubular water and electrolyte reabsorption (cations as well as
anions)
USES: Increased ICT, dialysis disequilibrium

16. THANK YOU