Diuretics

Question 1

Acetazoleamide

Answer 1

Carbonic Anhydrase Inhibitor

MoA: Self-limited NaHCO3 Diuresis and decrease total body HCO3- stores

–> decrease RBF and GFR

–> Diuresis and increase K+ excretion

–> increase urine pH (metabolic acidosis)

TX: gluacoma, acute mountain sickness, induce urinary alkalinization

ADVERSE: Hyperchloremic metabolic Acidosis (“ACID”azolamide causes ACIDosis)

–> renal stones and renal loss of K+

Question 2

Mannitol

Answer 2

OSMOTIC DIURETIC

MoA: increase tubular fluid osmolarity resulting increase ruine flow and decreased intracranial/intraocular pressures

–> acts on proximal tubule and thin limbs of loop of henle

USES: Drug overdose, elevated intracranial/intraocular pressure

ADVERSE: Pulmonary edema, Hyponatremia (nausea, headache, vomiting) hypernatremia (loss of water in excess of electrolytes)

CONTRAINDICATED IN impaired liver function and Anuria

Question 3

Furosemide (MoA)

Answer 3

NKCC inhibitors (loop diuretics)

MoA:

–> Inhibit Na+-K+-2Cl- cotransporter (NKCC) = inhibit reabsorption of solute from Thick ascending limb

–> Venodilation: decrease right atrial pressure and pulmonary capillary wedge pressure within minutes (IV)

–> Increase Fractional Ca2+ excretion (Loops lose Ca+)

–> increase fractional Mg2+ excretion (decreasing voltage-dependent paracellular transport

Question 4

describe the clinical indication and adverse effects of Furosemide

Answer 4

• Applications:

–> pulmonary edema

–> Congestive heart failure

–> acute renal failure

–> hypercalcemia: saline + loop diuretics

• ADVERSE

–> Hyponatremia, Hypokalemia, hypocalcemia, hypomagnesia, ototoxicity, hypERuricemia

Question 5

Chlorthalidone

Answer 5

NCC inhibitors (thiazides)

MoA: Inhibit DCT Na+-Cl- cotransporter (NCC) block coupled Na+ and Cl- reabsorption

–> decrease Ca2+ excretion

–> vasorelaxation (increase Ca2+ activated K+ channels) (much weaker)

TX OF: Hypertension, HF (control edema), hypercalciuria (stimulates Ca+ reabsorption), nephrolithiasis (reduces kidney stone formation), Nephrogenic diabetes insipidus (recovers abundance of aquaporin-2 channels)

Question 6

Amiloride

Answer 6

RENAL EPITHELIAL Na+ channel Inhibitors

MoA: block eptihelial Na+ channels on principal cells in the LATE distal convoluted tubule and initial connecting tubule and cortical collecting ducts

–> modest natriuesis and prevention of K+ loss

• USES: used as K+ sparing agents in HYPOKALEMIC ALKALOSIS

–> used with other diuretics to prevent to prevent hypokalemia

Question 7

Spironolactone (-ONE)

Answer 7

aldosterone-receptor antagonist

MoA: Antagonize aldosterone receptors in RENAL COLLECTING TUBUELS

–> decrease Na+ reabsorption resultin gin Natriuresis

–> decrease loss of K+ in exchange for Na+

USES: HF, hyperaldosteronism, edema and hypertension

ADVERSE:

–> HYPERKALEMIA

–> metabolic acidosis, (gynecosmastia, antiandrogen effects)

Question 8

describe the therapeutic effects of Aldosterone-receptor antagonists

Answer 8

Spironolactone, eplerenone

• Prevention of LV remodeling and cardiac fibrosis
• prevention of sudden cardiac death
• Hemodynamic effects (BP reduction, modest diuresis and natriuresis)
• Vascular effects

Question 9

Describe the clinical applications of Spironolactone

Answer 9

• Edema and hypertension (coadministered with thiazide or loop diuretics)
• Added to standard therapy of heart failure
• primary hyperaldosteronism (blocks receptors)
• refractory edema associated withs secondary aldosteronism (cardiac failure, hepatic cirrhosis, nephrotic syndrome, severe ascites)

Question 10

describe adverse effects of Apironolactone

Answer 10

- hyperkalemia (if you prevent the loss of K+)

• metabolic acidosis in cirrhotic patients
• effects due to bindign to other steroid receptors (gynecomastia, impotence, decreased libido, hirsutism)