Cardio: Heart Failure Drugs Flashcards
What are some drugs used for heart failure?
ACEi ARBs Carvedilol Diuretics (both loop and K+ sparing) Nitrates Digoxin Dobutamine/Dopamine Milrinone
What is the difference between systolic and diastolic heart failure?
Systolic=pump issue
-loss of contractility, usually due to volume overload and eccentric hypertrophy
Diastolic=relaxing issue
-hypertrophic and stiff ventricle leads to decrease in filling, contractility is fine though
Which of the two, systolic or diastolic, has a preserved ejection fraction?
Diastolic
-like I said, systolic is a bad pump so you cannot get the fluid out
What can make Diastolic HF worse?
A fib leads to less filling, making it worse
Tachycardiac means less filling
Increase in MAP
MOA of ACEi/ARBs
Blocks formation of/effect of Angiotensin II
- decrease afterload (vasodilation)
- blocks aldosterone (less Na+/water retention)
- -lowers BP
- decreasing remodeling
Clinical applications for Captopril (or other -prils)?
HTN, Systolic HF, diabetic nephropathy
What are some common toxicities of all ACEi?
Cough, angioedema, Teratogenic!!
-do not use w pregnancy
Also hyperkalemia, hyponatrema
Altered taste (mainly captopril)
Embryotoxic!
Which ACEi’s have longer half life, permitting once/day dosing and are more widely used today?
Benazepril and lisonopril
Clinical applications for losaratan (or other sartans)
HTN,
diabetic nephropathy,
CKD,
HF resistent to ACEis
What are some common toxicities of all ARBs?
Hypotension, hypoglycemia, hyperkalemia
Embryotoxic!
What make valsartan unique to the other ARBs?
It is not a prodrug, therefore does not need activation and is eliminated primarily in the feces
-works if poor renal function
What makes candesartan unique to other ARBs?
It has irreversible binding to AT1
Effects of Valsartan/Sacubitril?
Leads to increased secretion of BNP and ANP
-increases fluid loss, lowers BP
Valsartan is an ARB, so blocks Angiotensin II
Clinical applications of Valsartan/Sacubitril?
Heart failure w Reduced EF
How does Sacubitril work?
Inhibits neprilysin NEP through its active metabolite, LBQ657
Adverse effects of Valsartan/Sacubitril?
Hypotension, hyperkalemia, increased serum Creatinine
Angioedema**
MOA of carvedilol?
nonselective (inverse agonist) Beta- and alpha-adrenergic blocker
-B>a activity
Slows HR (less O2 use), protects from arrhythmias, reduces Renin
Clinical applications for carvedilol?
If stable:
- recent MI with rEF
- HFrEF (systolic HF)
- HTN (not first choice)
Toxicities of carvedilol?
Chest pain, discomfort, dizziness, lightheaded, swelling of LE, pain, SOB, bradycardia
Which B-blocker is good for HTN emergencies?
Labetalol
If a patient has had a recent MI and now has reduced ejection fraction, what should be given along with B-blockers?
ACEi
-this has been proven to reduce mortality
Would you use B-blockers in someone with COPD, Asthma, or heart blocks?
Nope
-can make all worse
What should you do when taking someone off a B-blocker?
Taper them off!
-abrupt removal can cause acute tachycardia, HTN and ischemia
MOA of Ivabradine?
blocks If (funny) channels -prolongs diastole and slows HR
Clinical applications of Ivabradine?
Treatment of HR>70 with systolic HF
can you use B-blockers with ivabradine?
Yes, but only maximally tolerated doses of B-blockers, or if they are contraindicated
Toxicities of Ivabradine?
Bradycardia, HTN (reflex), increase A-fib risk, heart block, SA arrest
Contraindications of Ivabradine?
Decompensated HF
-meaning regulation isn’t working
Hypotension, AV block, hepatic impairment
MOA of spironolactone
Competitive aldosterone antagonist
- decreases reabsorption of Na and water
- -lowers BP
Also antagonizes pro-fibrotic effect of aldosterone
Clinical applications of spironolactone
Tx of:
- HF without loss of K+**
- reduces fibrosis in HFrEF post MI**
- Primary hyperaldosteronism
What is interesting about spironolactones pharmacokinetics?
it is a steroid, so it is slow on, slow off
-single dose lasts for a few days
Adverse effects of spironolactone?
Hyperkalemia
Amenorrhea, hirsuitism, gynecomastia, impotence
Tumorigen
What can happen if you mix loop diuretics with digoxin?
Increases toxic effects!
-hypokalemia increases the effect of digoxin
MOA of loop diuretics?
NKCC blocker, so water will follow
- lowers fluid, therefore lowers preload and BP
- removes fluid congestion to bring heart to optimal stretch length
Where do loop diuretics work?
Thick ascending loop of Henle
Clinical applications of Furosemide
Loop diuretic for edema in:
-HF, cirrhosis, renal issues**
Lowers preload and BP
Toxicities in furosemide?
Loss of electrolytes (K, Na, Ca, Mg)
Hyperglycemia, Hyperuricemia
Ototoxic!*
-vertigo, tinnitus
Sulfa drug*
What loop diuretics have better oral absorption, so work better in HF?
Torsemide and butemide
What can be given as a loop diuretic in those w a sulfa allergy?
Ethacrynic acid
What drug drug interactions do you need to watch for with loop diuretics?
Digoxin
-less K+ can increase toxicity of digoxin
Ototoxic drugs
-mycin Abs!
What can be given with loop diuretics to prevent hypokalemia?
K+ sparing diuretics
-spironolactone
What class of diuretics loses the least amount of bicarb?
Loop diuretics
Hydrochlorothiazide MOA
Blocks NaCl cotransporter at distal tubule
-decreases Na and Water absorbed to lower BP
What is an off label use of Hydrochlorothiazide
Calcium nephrolithiasis
-counters loss of Ca+
Toxicities of Hydrochlorothiazide
Loss of electrolytes (K, Na, Mg)
Hyperglycemia, Hyperuricemia
Sulfa drug*
Which thiazide diuretic is a favorite of cardiologists?
Metolazone
Which thiazide diuretic is longest acting?
Chlorthalidone
What are some common causes of diuretic failure?
Nonadherance, excess salty diet
Decreased GFR
NSAID use
Isosorbide dinitrate decreases ___load while hydralazine decreases ___load
Isosorbide dinitrate decreases preload while hydralazine decreases afterload
What does hydralazine require to become activated?
COX activation, mediated by PGI
Clinical applications of hydralazine?
HTN and HF (especially African Americans, or if ACEi contra)
When is hydralazine used in HTN emergency?
In pregnancy!
Does hydralazine dilate arterioles or veins?
Arterioles
-decrease afterload
Does nitroglycerin dilate arterioles or veins?
Veins
-decrease preload
Adverse effects of hydralazine
angina pectoris, flushing, tachycardia, edema
pruritis**
drug-induced lupus**
MOA of digoxin
Inhibits Na/K ATPase
- increases Na and Ca in heart, increasing contractility (positive inotrope)
- directly suppresses AV node
Clinical applications of Digoxin
To..
- control RVR in a-fib
- Treat HF by increasing contractility of heart
How is digoxin administered?
Orally
-increases as CO and renal function decrease so needs loading dose!
Is digoxin safe in pregnancy?
Yup, safe to use in SVTs during pregnancy
Adverse effects of digoxin
Cholinergic effects (N/V, diarrhea), blurry yellow vision, arrythmias (PVC), AV block
these are the ones in FA
How does digoxin affect ANS activity?
Increases Vagus firing rate, so more response to SA node to ACh
How do you treat digoxin overload?
KCl
Lidocaine, Phenytoin (Class IB antiarrythmic)
Anti-digitalis Abs
First line Tx of Systolic HF?
ACEi or ARBs or ARNI in conjuction with B-blockers/aldosterone antagonists
Tx of Diastolic HF?
Control BP
-treat symptoms with diuretics
Do nitrates, PDE5 inhibitors, or digoxin have efficacy for treating HFpEF?
No, so dont use
If a patient is hyper/normotensive with Acute Decompensated HF, how should you treat?
Loop Diuretic + Vasodilator (nitrates/nitroprusside)
If a patient is hypotensive with Acute Decompensated HF, how should you treat?
Just a loop diuretic
If a patient has Decompesated HF and signs of symptomatic hypotension with end-organ dysfunction what should be given?
Dobutamine or Dopamine
and
Discontinue B-blockers if pt has moderate-severe end organ damage
MOA of milrinone
Selective PDE-3 inhibitor
-used as inotropic agent increasing cAMP
Clinical use of milrinone?
Used for unresponsive HF
Adverse effects of milrinone?
Ventricular arrythmias, SVTs, headache
MOA of Dobutamine
Increase B1/B2 activity (+) enantiomer
-increase HR and Contractility for cardiac shock
Block a-receptors (-) enantiomer
MOA of dopamine
Low doses=activates B1
-increase HR and contractility for shock and cardiac decompensation
What drugs should you avoid in decompensated HF?
Class I antiarrythmics (consider amiodarone instead),
CCBs,
NSAIDs
How do you know if digitalis is therapeutic or toxic based on ECG?
Therapeutic
-ice cream scoop
Toxic
-decoupled Atria and ventricular contraction or even PVCs
