Diuretics

Question 1

What is the purpose of diuretics?

Answer 1

To increase urine flow rate

Question 2

The extracellular matrix is high in what ions?

Answer 2

Sodium (140), Bicarbonate(25), Chloride(100)

Question 3

The intracellular matrix is high in what ions?

Answer 3

Potassium(125), Magnesium(40), Phosphate(150), Protein(40)

Question 4

Uses of diuretics

Answer 4

mobilize fluid, excrete fluid (edema, extracellular fluid), excrete electrolytes

Question 5

Classes of Diuretics

Answer 5

carbonic anhydrase inhibitors, thiazides and related agents, loop diuretics, potassium-sparing diuretics, osmotic diuretics, xanthines, ethanol, and water

Question 6

Carbonic Anhydrase Inhibitors

Answer 6

Prototype: Acetazolamide
Mechanism: inhibition of intracellular and extracellular carbonic anhydrase
Effects: weak diuretic, blocks Na+ and HCO3- reabsorption, increases Na+,HCO3-, and K+ excretion; inhibits formation of H+ and HCO3- intracellularly, inhibits Na+ and H+ luminal exchange, and Na+ and HCO3- basolateral cotransport
Uses: chronic glaucoma (decrease aqueous humor formation and intraocular pressure), prophylaxis of acute mountain sickness, urinary alkalization, not normally used as a diuretic
Adverse Effects: Metabolic acidosis (hypercholemic, decreased diuresis), Hypokalemia, drowsiness, tingling of extremities, and hypersensitivity (sulfa drug)

Question 7

Benzothiadiazides and Related Drugs

Answer 7

Thiazides: Hydrochlorothiazide, Chlorothiazide, and Polythiazide
Related Drugs: Chlorthalidone, Metalozone, Indapamide
Mechanism: inhibition of sodium chloride cotransporter on the luminal membrane of distal tubular cells (minimal effects at proximal convoluted tubule)
Effects: Modest diuretic that binds to Cl- binding site
Increases Na+, K+, Cl-, HCO3-, H2O excretion (10% of filtered load)
Decreases Ca2+ and uric acid excretion in chronic use
Uses: Hypertension, CHF, Cirrhosis, other edematous states, Hypercalciuria, Nephrogenic Diabetes Insipidus, Nephrotic Syndrome

Can be good in patients with osteoporosis
Be careful in patients with gout

Question 8

Thiazides and GFR

Answer 8

Thiazides are NOT effective if GFR

Question 9

Adverse Effects of Thiazides

Answer 9

Hypokalemia (can interact with digitalis), hypercalcemia, hyperuricemia (gout attacks), hyperglycemia, hypovolemia, hypersensitivity(because a sulfonamide)
can eventually lead to hyperlipidemia with chronic use (increased LDL, total cholesterol, and total TG)

Question 10

Loop Diuretics

Answer 10

Prototypic Drugs: Furosemide, Bumetanide, Torsemide, and Ethacrynic acid
Mechanism: inhibition of Na+-K+-2CL- cotransporter in luminal membrane of ascending limb of loop of Henle
Effects: increases Na+, K+, Ca2+, Cl-, and H2O excretion (25% excretion of filtered), various effects of HCO3-
Uses: Acute Pulmonary Edema, Edema of Cardiac, Hepatic, or Renal origin, Hypertension, and Hypercalcemia
Works in low GFR
Adverse Effects: hypovolemia, hypokalemia*, hyponatremia, hyperuricemia, hyperglycemia, hyperlipidemia, OTOTOXICITY (additive with other drugs like ahminoglycosides)

Ethacrynic Acid is not a sulfa!!! No hypersensitivity

Question 11

Potassium Sparing Diuretics

Answer 11

Aldosterone receptor antagonists and non steroidal renal epithelial Na+ channel inhibitors

Not sulfa drugs!

Question 12

Aldosterone Receptor Antagonists (K+ Sparing)

Answer 12

Spironolactone and Eplerenone
Mechanism: competitively inhibits the binding of aldosterone to mineralocorticoid receptor in late distal tubule and collecting duct cells
Effects: Increase Na+, Cl-, and H2O excretion (2-3% excretion of filtered), decrease K+ and H+ excretion
Often seen combined with thiazides or loop
Uses: Spironolactone - Primary Hyperaldosteronism, Prevent hypokalemia from thiazide or loop, drug of choice in hepatic cirrhosis patients and nephrotic syndrome
Eplerenone - hypertension and CHF post MI
Adverse Effects: hyperkalemia, gynecomastia* or menstrual irregularities

Question 13

Triameterene and Amiloride (K+ sparing)

Answer 13

Mechanism: inhibit luminal Na+ channel in late distal tubule and collecting duct
Uses: secondary hyperaldosteronism and prevention of hypokalemia
Adverse Effects: Hyperkalemia

Question 14

Osmotic Diuretics

Answer 14

Mannitol and Urea
Mechanism: freely filtered at glomerulus but poorly reabsorbed from the luminal fluid, little to no metabolism, given in hyper osmotic solution
Uses: maintain urine flow, oliguric acute renal failure, reduce intracranial or intraocular pressure, not useful for mobilizing edema
Adverse Effects: over expansion of extracellular fluid, alteration of Na+,K+ levels in blood