heart failure meds Flashcards
Pathophysiology of chronic heart failure
As the heart pumps become less effective, there is an increase volume of blood left in the ventricles at the end of each cycle, increasing the end-diastolic volume. Over time, the heart will be overstretched and contracts less forcefully.
What are heart failure meds
- Nitrates
- Beta blockers
- [non-selective] propranolol, pindolol, carvedilol
- [beta-1 selective] atenolol, bisoprolol, metoprolol
- [mixed - 3rd gen] nebivolol - Diuretics
- loop diuretics
- potassium sparing diuretics - hydralazine
- sacubitril-valsartan
- ivabradine
MOA of beta blockers
blocks beta adrenoreceptors on cardiac myocytes
decrease adenylate cyclase
decrease ATP conversion to cAMP
decrease PKA activation
decrease opening of Ca2+ channels
decrease entry of Ca2+
decrease activation of calcium induced calcium release
decrease activation of sarcoplasmic reticulum calcium
decrease calmodulin complex activation
decrease actin-myosin complex
decrease contractility of cardiac myocytes
MOA of loop diuretics
normally:
- Na+/K+/2Cl- cotransporters will reabsorb K+ from tubular lumen into the cell
- causes accumulation of K+ in the cells
- causes back diffusion of K+ into the tubular lumen
- generates a strong positive electrical potential in the tubular lumen
- creates a driving force for Ca2+ and Mg2+ reabsorption
MOA of loop diuretics:
- blocks Na+/K+/2Cl- cotransporter
- prevent accumulation of K+ in the cells
- decrease back diffusion of K+ into tubular lumen
- weakens the positive electrical potential in the tubular lumen
- decrease reabsorption of Ca2+ and Mg2+
- increase excretion of Ca2+ and Mg2+
(hypocalcaemia, hypercalciuria)
(hypomagnesemia, hypermagnaeuria)
Loop diuretics induce the synthesis of?
renal prostaglandins
Adverse effects of loop diuretics
Ototoxicity
Hypocalcaemia + hypercalcaeuria
Hypomagnesemia + hypermagnaeuria
MOA of potassium sparing diuretics
Spironolactone, Eplerenone inhibits aldosterone receptor
Triamterene, Amiloride inhibits Na+ channel
-> decrease Na+ reabsorption
-> decrease K+ secretion
-> decrease blood volume
-> decrease pre-load
Between spironolactone and eplerenone, which has a slower onset of action?
Spironolactone
Between triamterene and amiloride, which has a shorter half life?
triamterene is metabolised in the river and has shorter half life
MOA of hydralazine
- direct arteriole vasodilator
- inhibit IP3-induced release of calcium from smooth muscle cells sarcoplasmic reticulum
- reduces peripheral resistance + release of norepinephrine -> increase CO and venous return
In essential hypertension, when 1st line drugs are inadequate, give…
hydralazine orally
In acute onset, severe peripartum or post partum hypertension, give…
hydralazine IV
Hydralazine is contraindicated in…
Contraindicated in patients with Coronary Artery Disease due to hydralazine’s stimulation of sympathetic nervous system -> increase CO and increase O2 demand -> myocardial ischaemia as O2 demands cannot be met
MOA of sacubitril-valsartan
During heart failure
-> brain natriuretic peptide increases
Brain natriuretic peptide
-> promotes vasodilation, natriuresis, diuresis
-> antagonises RAAS
-> broken down by neprilysin
Sacubitril is a neprilysin inhibitor
-> prolong BNP effects -> good for HF
Neprilysin breaks down angiotensin II -> hence sacubitril will cause an accumulation of angiotensin II -> prolonged effects of angiotensin II -> bad for HF
Solution? Give sacubitril with valsartan (Angiotensin II Type 1 blocker)
Why can’t sacubitril-valsartan be used with ACE inhibitors?
Neprilysin breaks down bradykinin
ACE inhibitors prevent bradykinin inactivation
-> sacubitril will lead to the accumulation of bradykinin which will lead to angioedema
Sacubitril-valsartan can replace ACE inhibitors or used with other drugs normally used with ACE inhibitors
