Heart failure

Question 1

Types of HF drugs

Answer 1

1. ACE-I
2. AT1 blockers
3. beta blocker
4. diuretics (loop, potassium sparing)
5. sacubitril-valsartan
6. hydralazine
7. ivabradine
8. nitrates

Question 2

Sacubitril MOA

Answer 2

• inhibits neprilysin, prevents breakdown of BNP (promote vasodilation, natriuresis, diuresis)

Question 3

why must valsartan be combined with saculbitril

Answer 3

• neprilysin also breaks down AngII -> saculbitril cause accumulation of AngII -> exacerbate HF via water retention thus need AT1 blocker

Question 4

sacubitril-valsartan clinical indication

Answer 4

HFrEF

Question 5

sacubitril-valsartan adverse effects (RARE) (4)

Answer 5

• hypotension
• hyperkalemia
• cough and angioedema (due to excessive bradykinin -> neprilysin breaks down bradykinins)
• renal failure

Question 6

loop diuretics examples

Answer 6

furosemide

Question 7

loop diuretic MOA

Answer 7

• inhibit Na+/K+/2Cl- transporter in ascending limb -> K+ cannot be excreted thus Mg2+ and Ca2+ excreted into urine instead -> diuresis
• induce renal PG synthesis -> increase renal blood flow and GFR -> diuresis
• furosemide -> increase renal blood flow

Question 8

loop diuretic mode of administration, duration, elimination (3)

Answer 8

• IV injection, rapid response
• duration of effect -> 2-3 hours
• eliminated by tubular secretion and glomerular filtration

Question 9

loop diuretics clinical indications (4)

Answer 9

• ACUTE pulmonary edema/ peripheral edemas
• ACUTE hyperkalemia
• ACUTE renal failure
• ANION OVERDOSE

*acute relief due to fast onset of action

Question 10

loop diuretics adverse effects

Answer 10

• hypokalemic metabolic alkalosis (reduced K+ retention)
• ototoxicity -> NO aminoglycoside
• hyperuricemia
• hypomagnesemia

Question 11

potassium sparing diuretics examples

Answer 11

• spironolactone
• eplerenone
• triamterene
• amiloride

Question 12

spironolactone, eplerenone MOA

Answer 12

• mineralocorticoid receptor antagonists
• blocks binding of aldosterone receptor -> cannot activate Na channel to increase Na reabsorption -> more urine

Question 13

triamterene, amiloride MOA

Answer 13

• blocks Na channel directly -> decrease Na reabsorption -> more urine

Question 14

spironolactone onset of action

Answer 14

• very slow, requires a FEW DAYS

Question 15

triamterene metabolism and Thalf (2)

Answer 15

• metabolized in the liver
• shorter Thalf than amiloride

Question 16

amiloride metabolism

Answer 16

• excreted unchanged in urine

Question 17

potassium sparing diuretics clinical indications

Answer 17

• diuretic
• hyperaldosteronism

Question 18

potassium sparing diuretics adverse effects (4)

Answer 18

• hyperkalemia thus metabolic acidosis
• GYNECOMASTIA (spironolactone)
• acute renal failure (triamterene + indomethacin)
• kidney stones (triamterene)

Question 19

hydralazine MOA

Answer 19

• direct arterial vasodilator (inhibits IP3 induced release of calcium from sarcoplasmic reticulum in smooth muscles) -> reduce peripheral resistance -> compensatory release of epinephrine (sympathetic stimulation) -> increase venous return and CO

Question 20

hydralazine clinical indications (3)

Answer 20

• HFrEF; oral, combine with isosorbide dinitrate
• hypertension; oral (when 1st line fails)
• acute peri partum/ post partum hypertension

Question 21

hydralazine PK

Answer 21

IV: 5-30mins onset; 2-6hours duration
oral: 20-30mins onset; 2-4hours duration

Question 22

hydralazine adverse effects 4

Answer 22

• flushing,
• hypotension
• tachycardia (baroreflex associated sympathetic activation)
• hydralazine induced lupus syndrome (HILS)

Question 23

hydralazine contraindication

Answer 23

• coronary artery disease (due to sympathetic stimulation by hydralazine)