CHF Pharm Flashcards
Difference between treating HFpEF vs HFrEF
Different functional deficiencies of the heart. HFrEF is due to a systolic dysfunction, therefore we can improve the condition by reducing preload and afterload
What is the suffix for ACEi drugs?
- pril
* Captopril, Enalapril, Benzapril, Lisinopril
What is the suffux for ARBs (angiotensin receptor blockers)?
- sartan
* Losartan, Valsartan, Candesartan
Which B-blockers are used to treat heart failure?
- Carvedilol***
- Metoprolol
- Bisoprolol
What aspects of HF do ACEi and ARB’s help with?
Decreased action of angiotensin II
- decreased vasoconstriction (decreasing afterload)
- decreased aldosterone secretion (decreasing preload)
- decreased cell proliferation and remodeling (vascular stenosis)
Clinical indications for ACEi
*Captopril, Enalapril, Benzapril, Lisinopril
HTN, HFrEF, diabetic neuropathy
Classic toxicities associated with ACEi
*Captopril, Enalapril, Benzapril, Lisinopril
- Cough
- Angioedema
- Fetal toxicity (teratogenic)
Which ACEi are most commonly prescribed today?
Lisinopril, Benazepril
*longer half-life permits 1x/day dosing
ACEi MOA
*Captopril, Enalapril, Benzapril, Lisinopril
Competitively binds ACE, preventing the conversion of angiotensin I to angiotensin II
Clinical indications for ARB’s
*Losartan, Valsartan, Candesartan
HF if intolerant to ACEi
HTN
Classic toxicities associated with ARB’s
*Losartan, Valsartan, Candesartan
- Cough (not as bad as ACEi)
- Fetal toxicity (teratogenic)
*angioedema is feared but should not happen
ARB MOA
*Losartan, Valsartan, Candesartan
Non-peptide angiotensin II receptor antagonist (AT1)
Which ARB is metabolized to its active form in the liver by CYP enzymes?
*Losartan, Valsartan, Candesartan
Losartan
Which ARB is notable for not being a prodrug, therefore it does not need to be metabolized to its active form in the liver?
*Losartan, Valsartan, Candesartan
Valsartan
*may be useful in pt intolerant to ACEi who also has liver failure
Which ARB is noteworthy because it is able to irreversibly bind?
*Losartan, Valsartan, Candesartan
Candesartan
ACEi and ARB contraindications
- Not tolerated
- Pregnant (teratogenic)
- Hypotensive
- Creatinine .3 mg/dL
- Hyperkalemia (okay up to 5.5)
Sacubitril MOA
*valsartan/sacubitril
Inhibits NEP (enteropeptidase that breaks down BNP and ANP)
- leads to increased levels of ANP and BNP, which act as a check on RAAS, leading to decreases in all of renin, aldosterone, ADH
- Considered best initial treatment for HFrEF… but $$$
Which B-blockers can be used in HF?
Carvedilol***
Bisoprolol
Metoprolol
*should be given to all HF patients with LVEF <40% unless contraindicated
Clinical indications for Carvedilol
- HFrEF to prevent symptomatic HF
- rEF after MI or ACS
*Pt must be stable! Don’t want to slow down their heart if they already are not stable. Start with low dose.
Carvedilol MOA
Non-selective B>a blocker with no sympathomimetic activity
- Lowers HR
- keeps heart responsive to sympathetic drive
Carvedilol contraindications
- Bronchospastic disease (due to B2 block)
- Symptomatic bradycardia
WARNING: do not abruptly stop B-blockers, can lead to acute tachycardia, HTN, ischemia
Ivabradine MOA
Specific inhibition of Funny Na channels in the SA node
- prolongs diastole and slows HR
- called hyperpolarization-activated cyclic neucleotide gated (HCN) Funny channels
Ivabradine clinical applications
funny channel blocker
Treat HR >70 bpm in pt with stable, sinus rhythm, symptomatic HF with LVEF <35% who are on max B-blocker dose or intolerant to B-blockers
Ivabradine contraindicatoins
funny channel blocker
-ADHF, hypotension, bradycardia, heart block, arrhythmia
Spironolactone, Eplerenone MOA
Competitive antagonist of aldosterone receptors
*Eplerenone is more selective to aldosterone receptor
- K sparing diuretic (aldosterone inhibition)
- Antagonizes pro-fibrotic effects of aldosterone on local vasculature
Spironolactone clinical applications
- Reduce fibrosis HFrEF and post-MI HF
- Counteracts K loss induced by other diuretics in treatment of HTN, HF
How do diuretics help with HF?
Decrease edema (congestion)
Loop diuretic MOA
Furosemide, Toresemide, Bumetanide
Ethactynic acid
Block Na K 2Cl cotransporter in the TAL
- Prevents reabsorption of Na, K, Cl
- Prevents paracellular reabsorption of Ca and Mg
Clinical applications of loop diuretics
Furosemide, Toresemide, Bumetanide
Ethactynic acid
- Edema
- HF (decreases preload)
- HTN
*also works in pt with low GFR (unlike thiazides)
What toxicities are associated with loop diuretics (furosemide)?
Hypokalemia, Hyponatremia, Hypochloremia (inhibition of NKCC cotransporter)
- also hypomagnesemia and hypocalcemia
- hyperglycemia and hyperuricemia
- **Ototoxicity
- **Sulfonamide! allergy risk
Which loop diuretic is not a sulfonamide, and can therefore be used in patients with sulfa allergies?
Ethacrynic acid
Diuretic use in HF (1st line, 2nd line, 3rd line)
- Loop diuretic
- add K sparing diuretic if needed (hypokalemia)
- add thiazide if more diuresis needed
Thiazide diuretic MOA
*Hydrochlorothiazide, Chlorothiazide, Chlorthlidone, Metolazone
Inhibits Na reabsorption via blocking Na/Cl cotransporter in the DCT
*K-losing diuretic
Clinical applications of thiazide diuretics
*Hydrochlorothiazide, Chlorothiazide, Chlorthlidone, Metolazone
- HTN
- Ca nephrolithiasis
- Adjunct tx in HF
*not effective in pt with low GFR
What toxicities are associated with thiazide diuretics?
*Hydrochlorothiazide, Chlorothiazide, Chlorthlidone, Metolazone
- Hypokalemia, Hyponatremia, Hypomagnesemia, Hypocholoremia
* Sulfonamide!!!
What thiazide diuretic is long acting, and commonly used as an adjunct diuretic in heart failure?
Metolazone
Nitrate drug MOA
*Nitroglycerin, Isosorbide dinitrate
MOA: forms NO, more prominently causes venodilation
Clinical application for nitrate drugs
- Angina pectoris
- Acute decompensated HF (ADHF)
Which nitrate drug is administered orally and has a slower onset of action, and may specifically be used for HFrEF
Isosorbide dinitrate
What drug causes direct vasodilation of arterioles and is specifically indicated for African Americans with HFrEF?
Hydralazine
- hydralazine/isosorbide nitrate combo drug
- can also treat HTN
*may cause drug induced lupus-like synd
How do vasodilators help in the treatment of HFrEF?
Reduced afterload (decreased work needed to be done by heart)
Digoxin MOA
inhibition of Na/K ATPase in myocardial cells, indirectly stimulating Na/Ca exchanger, leading to increased Ca within the myocardial cell
- increased Ca = increased contractility
- suppresses AV conduction via increased vagal tone, slowing HR
Clinical application of Digoxin
Not commonly used any longer
- Controls Afib
- HF
- can only be administered if HR is normal
What happens in digoxin toxicity?
Ca overload can cause arrhythmias
Major Digoxin drug interaction
Diuretics
- digoxin competes with K at the Na/K ATPase
- diuretics cause hypokalemia
- hypokalemia increases digoxin binding, increasing likelihood of toxicity
Sympathomimetics used to treat acute decompensated HF in the ER (rescue therapy)
*indicated if symptomatic hypotension with end-organ dysfunction despite adequate filling pressures
Dobutamine, Dopamine
Milrinone MOA
PDE3 inhibitor, increases cAMP and therefore contractility
*used as inotropic therapy in pt unresponsive to dobutamine or dopamine
