heart failure drugs

Question 1

drugs for HF

Answer 1

beta blockers, sacubitril-valsartan, loop diuretics, potassium sparing diuretics, hydralazine, isosorbide mononitrate/dinitrate, ivabradine, cardiac glycosides,

Question 2

mechanism of loop diuretics

Answer 2

1. selective inhibition of Na+/K+/2Cl- transporter in thicking ascending limb –> less K+ in urine –> greater excretion of Mg2+ and Ca2+
2. greater excretion of Na+ and Cl- –> less driving force for water reabsorption
3. induce renal PG synthesis

Question 3

mechanism of potassium sparing diuretics

Answer 3

1. inhibits aldosterone from binding to aldosterone receptor (spironolactone and eplereone) –> less Na+ and H2O reabsorption, less K+ secretion
2. inhibit Na+ channels reducing Na+ reabsorption and K+ secretion

Question 4

adverse effects of loop diuretics

Answer 4

• hyponatremia
• hypokalemia
• hypomagnesemia
• ototoxicity
• metabolic alkalosis

Question 5

adverse effects of K+ sparing diuretics

Answer 5

• hyperkalemia
• metabolic acidosis
• gynecomastia (spironolactone)
• acute renal failure (triamterene + indomethacin)
• kidney stone (triamterene)

Question 6

mechanism of hydralazine

Answer 6

Inhibits IP3-induced release of calcium from smooth muscle endoplasmic reticulum → arteriole vasodilation → reduces peripheral resistance –> increases cardiac output

Question 7

mechanism of sacubitril-varsartan

Answer 7

• sacubitril is a neprilysin inhibitor –> prolongs BNP effects that antagonises RAAS (good) but neprilysin breaks down Ang II
• hence add on valsartan

Question 8

hydralazine is used with what drug

Answer 8

isosorbide nitrate

due to hydralazine activating the baroreflex sympathetic activation

Question 9

hydralazine (alone) is contraindicated in

Answer 9

coronary artery disease

Question 10

mechanism of isosorbide mononitrate/dinitrate

Answer 10

• venodilation –> reduced preload
• arteriolar dilation –> reduced dilation

this decreases cardiac load and blood pressure

Question 11

mechanism of cardiac glycosides

Answer 11

• inhibit Na+/K+ ATPase pump in cardiac myocytes –> lesser Na+ efflux, increase in intracellular Na+ concentration
• less Ca2+ efflux –> stronger systolic contraction
• increased cardiac output would mean
  1. lesser carotid sinus firing –> less activation of SNS –> less afterload (because SNS causes vasoconstriction of peripheral vessels)
  2. more renal blood flow –> less activation of RAAS –> less preload

Digoxin also reduces QT, ST and causes inversion of T. This increases parasympathetic activity and decreases AV conduction, increasing PR interval and decreasing ventricular rate → helpful for arrhythmias like AF

Question 12

adverse effects of cardiac glycosides

Answer 12

more severe dysrhythmia like VF, AV block; GI effects like anorexia, nausea,vomiting; CNS effects like headache, fatigue, confusion, blurred vision