E4. Chronic HFREF Treatment Flashcards
Left Sided HF
HFrEF
In the pathophysiology of HF, what component do beta-blockers address?
Catecholamine release.
In the pathophysiology of HF, what component does RAAS inhibition and MRAs address?
The Juxtaglomerular Response
In the Pathophysiology of HF, what component do MRAs, Nephrylisin inhibitors, and SLGT2is address?
Sodium and Water retention.
In the pathophysiology of HF, what do beta-blocker and hydralazine act address?
Alpha-1 Stimulation.
What five drug classes are associated with mortality benefit in HF?
- Beta-blockers
- RAAS inhibitors
- Mineralocorticoid Receptor Antagonists
- SGLT2i
- Vaso/Venodilators
What three beta-blockers are shown to have mortality benefits in HF?
- Carvedilol
- Metoprolol Succinate
- Bisoprolol
Which SGLT2i are shown to have morality benefit in HF?
- Dapagliflozin
- Empagliflozin
Which vaso/venodilators are proven to have mortality benefit in HF?
- Hydralazine
- Isosorbide dinitrate
What drugs are shown to have reduce morbidity only in HF?
- Ivabradine
- Vericiguat
- Digoxin
- Diurectics
Which morbidity reducing drug should be used for patients on a max beta-blocker, who remain symptomatic with a heart rate above 70.
Ivabradine
Which morbidity-reducing drug is a soluble guanylate cyclase stimulator?
Vericiguat
Which morbidity reducing drug is a mild positive inotrope?
Digoxin
T or F: Diurectics are shown to reduce morbidity in HF?
True.
In what situation should you add hydralazine-nitrates to a heart failure patient regimen?
- African American NYHA III-IV Heart Failure
- Patient can not tolerate RAAS inhibitors.
Entresto Generic Name
Valsartan/Sacubitril
In Entresto, what is the mechanism of the sacubitril component?
It blocks the breakdown of brain natriuretic peptide. This leads to natriuresis and vasodilation.
What is the only contraindication to entresto? (Any RAAS inhibitor really)
Pregnancy
______ require a 36 hour wash out period prior to the initiation of entresto due the possibility of an acute bradykinin increase causing angioedema.
ACE-inhibitor.
Entresto ADE (3)
- Hyperkalemia
- Acute Renal Failure (Bilateral renal artery stenosis)
- Hypotension
At what potassium level should we not initiate entresto?
5.5 mmol/L
At what k+ level should we discontinue entresto?
5.6 mmol +
ACE-Inhibitor Contraindications
- History of angioedema
- Entresto use within 36 hours.
- Bilateral renal artery stenosis.
RAAS inhibitors should not be initiated at a K+ level above _____.
5.0 mmol/L
RAAS inhibitors should be discontinued at a K+ level above _____.
5.6 mmol/L
Rhabdomyolysis is a side effect of ____ (ACEi or ARB)
ARB
Entresto (Sacubitril/Valsartan) Target Dose
97/103 mg TWICE DAILY
Lisinopril Target Dose in HF
20-40 mg once daily
Valsartan Target Dose in HF
160 mg Twice Daily
______ should be tapered upon discontinuation due to the risk for rebound tachycardia.
Beta-blockers
_____ may mask the symptoms of hypoglycemia in patients with diabetes.
Beta-Blockers
____ should be used with caution in patients with severe bronchospastic diseases.
Beta-blockers.
Bisoprolol Brand Name
Zebeta
Bisoprolol Target Dose for HF
10 mg once daily.
Toprol XL generic name
Metoprolol succinate
Toprol XL target dose
200 mg Once daily
Coreg Target Dose
25 mg twice daily
> 85 kg: 50 mg twice daily.
What beta-blocker must be adjusted for patients who weigh more than 85 kg?
Coreg (Carvedilol)
What are the three contraindications for MRAs in HF?
- K+ (>5)
- Anuria
- CrCl <30 ml/min
Which MRA is a CYP3A4 substrate?
Eplerenone
Which MRA is associated with gynecomastia, breast tenderness, impotence.
Spironolactone
Which MRA is associated with increased triglycerides?
Eplerenone.
What are the ADEs of MRAs
- Dehydration
- Hyperkalemia
- Hyponatremia
- Dizziness
- Cardiac Arrythmias
_______ have the following monitoring parameters:
Monitor Electrolytes and renal function at 2-3 days following initiation, and then 7 days after initiation/titration. Then, check monthly for 3 months, then every 3 months afterwards.
MRAs
Spironolactone Target Dose in HF.
25-50 mg once daily.
What does competitive antagonism at the mineralocorticoid receptor lead to?
- Decreased Sodium Reabsorption
- Increased Potassium Reabsorption.
____ increases urine output by osmotic diuresis (glucose excretion). These are proposed to improve cardiac fibrosis.
SGLT2is
Dapagliflozin is contraindicated below and eGFR of ______.
30 mL/min
Empagliflozin is contraindicated below an EGFR of ____.
20 mL/Min
This class is associated with Genetic Mycotic Infections, Hypoglycemia, and Euglycemic Ketoacidosis.
SGLT2i
Dapagliflozin Target Dose
10 mg once daily.
Empagliflozin Target Dose
10 mg once daily.
This drug class, inhibits sodium, chloride, and potassium reabsorption in the thick ascending limb of the nephron.
Loop Diurectics.
Loop Diurectic Contraindications.
- Anuria
- Hypersensitivity to Sulfa Drugs.
Loop Diuretic Black Box Warning
Potent diuretic, at high doses may lead to profound fluid and electrolyte loss.
This drug class is associated with:
~Hyponatremia, hypokalemia, hypomagnesesemia, hypocalcemia, hypochloremia.
~Metabolic Acidosis
~Hyperuricemia
~Orthostatic Hypotension
~Dizziness
Loop Diurectics
This Drug class is associated with:
1. Acute Kidney Injury
2. Ototoxicity
Loop Diurectics
Which loop diuretic should be considered if a patient has a true sulfa allergy?
Ethacrynic Acid.
What conditions increase the loop diuretic threshold?
- Chronic Loop Diuretic Use
- AKI/CKD
- Heart Failure (Gut Edema)
In heart failure, when should loop diuretics be added?
When they are experiencing signs of congestion (hypervolemia).
What dose should be initiated in a loop diuretic naive patient with congestion?
20-40 mg Furosemide.
What may need to be prescribed with a loop diuretic to maintain electrolyte balance?
Potassium
What can be added to address resistance to loop diuretics?
Thiazide Diuretics.
Resistance to _______ results due to reduced GFR, HF, and gut edema.
Loop Diuretic Resistance
Furosemide Oral Starting Dose
40 mg
Furosemide IV Starting Dose
20 mg
Torsemide Oral Starting Dose
20 mg
Torsemide IV Starting Dose
20 mg
Bumetanide Oral Starting Dose
1 mg
Bumetanide IV Starting Dose
1 mg
Ethacrynic Acid Oral Starting Dose
50 mg
Ethacrynic Acid IV Starting Dose
50 mg
_______ is a vasodilator which is associated with Drug Induced Lupus Erythematosus.
Hydralazine.
This vasodilator is contraindicated with recent PDE5 inhibitor or riociguat use.
Isosorbide Dinitrate.
BiDil
20 mg isosorbide dinitrate/37.5 mg hydralazine.
When is Ivabradine recommended for HFrEF?
NYHA II-III, with normal sinus rhythm but a HR above 70 bpm despite maximal beta-blocker use.
When is Vericiguat recommended in HFrEF?
NYHA II-III with an LVEF < 45%, recent HF hospitalization, and elevated BNP.
When is Digoxin recommended?
Symptomatic HF
When are polyunsaturated fatty acids recommended in HF?
Occasionally to reduce HF hospitalizations.
This drug inhibits the hyperpolarization of cyclic nucleotide-gated channels (f-channels) within the SA node of cardiac tissue. This leads to disruption of the funny channel leading to prolonged diastolic depolarization, slowing firing in the SA node and reducing HR.
Ivabradine
Corlanor
Ivabradine
Ivabradine CI
- Severe Hepatic Impairment
- ADHF
- Clinically Significant Hypotension
- Sick SInus Syndrome
- Sinoatrial Block
- Third Degree AV Block
This drug is associated with causing bradycardia and atrial fibrillation.
Ivabradine.
This drug enhances the production of BMP by directly stimulating sGC independent of NO and enhances sGC sensitivity to endogenous NO.
This increases cGMP production, leading to smooth muscle relaxation and vasodilation.
Vericiguat (Verquvo)
Vericiguat CI
Pregnancy
Vericiguat DI
PDE5 inhibitors.
What drug covered in this section requires a negative pregnancy test prior to initiation?
Vericiguat.
This drug inhibits sodium/potassium ATPase pump in myocardial cells. –> This leads to a transient increase in intracellular sodium. This leads to an increase in calcium leading to depolarizations and increased contractility.
May also improve baroreflex sensitivity.
Digoxin.
This drug used to reduce morbidity in HF patients is a major p-glycoprotein substrate, and minor CYP3A4 substrate.
Digoxin.
Goal Digoxin Serum Trough Concentration
0.5-0.9 ng/mL
Digoxin ADE
- Arrythmia
- Heart Block
- GI/Neurological Side Effects
This morbidity reducing drug for HF, is on the BEERS list.
Digoxin.
What are the risk associated to Digoxin?
- Cardiac Arrythmias
- GI symptoms
- Neurological Symptoms
When may digoxin be initiated?
A patient is already on other GDTM and still symptomatic.
What medications should be avoided in HFREF?
- Non-DHP CCB
- Class 1C Antiarrhytmic Drugs and Dronedarone
- TZDs (azones)
- DPP-4s (gliptins)
- NSAIDs.
