Drugs for treatment of heart failure

Question 1

MOA of sodium nitroprusside

Answer 1

Release NO that causes vasodilation
Reduce preload and afterload → decrease cardiac load and BP → treat CHF

See MOA of nitrates for more detailed explanation

Question 2

Adverse effects of sodium nitroprusside

Answer 2

1. Hypotension
2. Cyanide poisoning
3. Methemoglobin > cellular hypoxia

Question 3

Examples of Loop Diuretics (most efficacious diuretic agents)

Answer 3

Sulfonamide derivatives: furosemide, bumetanide

ethacrynic acid

Question 4

MOA of Loop Diuretics

Answer 4

1. Loop diuretics selectively inhibit the luminal Na+/K+/2CL- transporter in the thick ascending limb of Henle’s loop
2. Loop diuretics cause an increase in Mg2+ and Ca2+ excretion
3. Loop diuretics induce renal PGs synthesis. NSAIDs (aspirin, indomethacin) interfere with the actions of loop diuretics by reducing the PGs synthesis
4. Furosemide increases renal blood flow

Question 5

PK of Loop diuretics

Answer 5

1. rapidly absorbed, response extremely rapid following IV injection
2. DOA of furosemide: 2-3H
3. eliminated by tubular secretion as well as glomerular filtration

Question 6

Clinical uses of Loop Diuretics

Answer 6

1. acute pulmonary oedema and other oedema
2. acute hyperkalemia
3. acute renal failure
4. anion overdose: toxic ingestions of bromide, fluoride, and iodide

Question 7

Adverse effects of Loop Diuretics

Answer 7

1. hypokalemic metabolic alkalosis
2. ototoxicity (avoid use together with aminoglycoside antibiotics, if possible)
3. Hyperuricemia
4. Hypomagnesemia

Question 8

Examples of Thiazides (most widely used diuretic agents)

Answer 8

1. Hydrochlorothiazide
2. Indapamide
3. Clorthalidone

Question 9

MOA of Thiazides

Answer 9

1. inhibit NaCl reabsorption by blocking the Na+/Cl- transporter
2. enhances Ca2+ reabsorption in DCT
3. action of thiazides depends in part on renal PGs synthesis, NSAIDs (aspirin, indomethacin) interfere with the actions of thiazide by reducing the PGs synthesis

Question 10

Clinical uses of thiazides

Answer 10

1. Hypertension
2. CHF
3. nephrolithiasis due to idiopathic hypercalciuria
4. nephrogenic diabetes insipidus

Question 11

Adverse effects of thiazides

Answer 11

1. Hypokalemic metabolic alkalosis
2. Hyperuricemia
3. Hyperglycaemia
4. Hyperlipidemia
5. Hypoatremia

Question 12

Examples of potassium-sparing diuretics

Answer 12

1. spironolactone
2. triamterene
3. amiloride
4. eplerenone

Question 13

MOA of Spironolactone and Eplerenone

Answer 13

Competitively bind to aldosterone receptors in the late distal convoluted tubule and the collecting duct → inhibition of the effects of aldosterone → decreased Na+ reabsorption and K+ excretion → diuresis

Question 14

MOA of triamterene and amiloride

Answer 14

direct inhibition of the epithelial sodium channels (ENaC) in the distal convoluted tubule and the collecting duct → reduced Na+ reabsorption and reduced K+ secretion → diuresis

Question 15

PK of potassium-sparing diuretics

Answer 15

1. spironolactone has a rather slow onset of action, requiring several days before full therapeutic effect is achieved
2. triamterene is metabolised in the liver, shorter half-life and must be given frequently than amiloride, amiloride is excreted unchanged in the urine

Question 16

Clinical uses of potassium-sparing diuretics

Answer 16

1. diuretics

2. hyperaldosteronism

Question 17

Adverse effects of potassium-sparing diuretics

Answer 17

1. hyperkalemia
2. metabolic acidosis
3. gynecomastia (not with eplerenone)
4. acute renal failure (triamterene + indomethacin)
5. kidney stones (with triamterene)