Types of HF drugs
- ACE-I
- AT1 blockers
- beta blocker
- diuretics (loop, potassium sparing)
- sacubitril-valsartan
- hydralazine
- ivabradine
- nitrates
Sacubitril MOA
- inhibits neprilysin, prevents breakdown of BNP (promote vasodilation, natriuresis, diuresis)
why must valsartan be combined with saculbitril
- neprilysin also breaks down AngII -> saculbitril cause accumulation of AngII -> exacerbate HF via water retention thus need AT1 blocker
sacubitril-valsartan clinical indication
HFrEF
sacubitril-valsartan adverse effects (RARE) (4)
- hypotension
- hyperkalemia
- cough and angioedema (due to excessive bradykinin -> neprilysin breaks down bradykinins)
- renal failure
loop diuretics examples
furosemide
loop diuretic MOA
- 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
loop diuretic mode of administration, duration, elimination (3)
- IV injection, rapid response
- duration of effect -> 2-3 hours
- eliminated by tubular secretion and glomerular filtration
loop diuretics clinical indications (4)
- ACUTE pulmonary edema/ peripheral edemas
- ACUTE hyperkalemia
- ACUTE renal failure
- ANION OVERDOSE
*acute relief due to fast onset of action
loop diuretics adverse effects
- hypokalemic metabolic alkalosis (reduced K+ retention)
- ototoxicity -> NO aminoglycoside
- hyperuricemia
- hypomagnesemia
potassium sparing diuretics examples
- spironolactone
- eplerenone
- triamterene
- amiloride
spironolactone, eplerenone MOA
- mineralocorticoid receptor antagonists
- blocks binding of aldosterone receptor -> cannot activate Na channel to increase Na reabsorption -> more urine
triamterene, amiloride MOA
- blocks Na channel directly -> decrease Na reabsorption -> more urine
spironolactone onset of action
- very slow, requires a FEW DAYS
triamterene metabolism and Thalf (2)
- metabolized in the liver
- shorter Thalf than amiloride
amiloride metabolism
- excreted unchanged in urine
potassium sparing diuretics clinical indications
- diuretic
- hyperaldosteronism
potassium sparing diuretics adverse effects (4)
- hyperkalemia thus metabolic acidosis
- GYNECOMASTIA (spironolactone)
- acute renal failure (triamterene + indomethacin)
- kidney stones (triamterene)
hydralazine MOA
- 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
hydralazine clinical indications (3)
- HFrEF; oral, combine with isosorbide dinitrate
- hypertension; oral (when 1st line fails)
- acute peri partum/ post partum hypertension
hydralazine PK
IV: 5-30mins onset; 2-6hours duration
oral: 20-30mins onset; 2-4hours duration
hydralazine adverse effects 4
- flushing,
- hypotension
- tachycardia (baroreflex associated sympathetic activation)
- hydralazine induced lupus syndrome (HILS)
hydralazine contraindication
- coronary artery disease (due to sympathetic stimulation by hydralazine)
