Wolff Heart Failure Drugs Flashcards
What class does Captopril fall under, what does it do, and what are its clinical applications?
- ACEI (“pril”)
- prevents angiotensin I converting to angiotensin II therefore:
- lowers AT II levels
- increases renin plasma levels
- Decreases aldosterone secretion
- Lowers BP overall
- Used for Htn, HFrEF, and diabetic neuropathy
What are the toxicities of Captopril?
- Cough is #1 reason people stop taking ACEI’s
- Angioedema (fatal stop immediately)
- Fetal toxicity (black box warning)
What class does Losartan fall under, what does it do, and what are it’s applications?
- ARB (“sartan”)
- its a non peptide angiotensin II receptor antagonist
- Leads to more complete inhibition of the RAS than ACEI’s
- doesn’t potentiate bradykinin
- Used in:
- Diabetic nephropathy
- Htn
- HF
Losartan has a higher selectivity for ___ than ___ receptor.
Losartan has a higher selectivity for AT1** than **AT2 receptor.
Toxicities of Losartan?
- Fetal toxicity
- Angioedema (?)
- AE’s are more common in those with diabetic nephropathy
What is “noteworthy” about Valsartan?
It is not a prodrug meaning that it doesn’t required activation by the liver and it is excreted in feces relatively un changed
ACEI and ARB should be administered to who? (ACEI are slightly preferred to ARB’s)
- all patients with LV systolic failure o LV dysfunction without HF unless:
- not tolerated (try ARB)
- Pregnant
- Hypotensive
- Serum creatinine >3
- Hyperkalemia
What are the renal/adrenal effects of ANP?
- Increased GFR
- Decreased renin and aldosterone secretion
- decrease Na and water reabsorption in collecting duct
- Decrease ADH secretion and it’s effects in collecting duct
What is the MOA of Valsartan/Sacubitril?
- Sacubitril is prodrug that inhibits Neprilysin
- Valsartan is ARB that is not a prodrug
What are the effects and indications for Valsartan/Sacubitril?
- Neutral endopeptidase blockage leads to increasesd levels of ANP & BNP
- Valsartan antagonizes AT1 receptors
- Used for Heart failure
Common AE’s of Valsartan/Sacubitril?
- Hypotension
- Hyperkalemia
- Increased serum creatine
Angioedema is not common, but is serious
What classes of drugs/drugs are used to prevent deterioration of cardiac function?
- ACEI/ARB
- Beta adrenergic blockers
- Spironolactone/Eplenerone
Heart failure ___ sympathetic activity which will result in, ____ HR, ____ contractility, and__vascular resistance.
Heart failure increases** sympathetic activity which will result in, **increased HR, increased** contractility, and_increased_** vascular resistance.
What are the three Beta Blockers that are used for heart failure?
- Metoprolol
- Bisoprolol
- Carvedilol
How is Carvedilol different than Metoprolol and bisoprolol for patients with HF?
- Inverse agonist at B2 receptors which are present in the heart
- “biased” ligand that causes phosphorylation of cytoplasmic tail of receptor or interaction with B-arrestin and downstream signaling occurs
What is Carvedilol’s MOA?
- nonselective beta and alpha adrenergic blocker
- blocks Beta more than alpha
Carvedilol clinical uses?
- Given if stable to prevent symptomatic HF
- Given if there is a recent or remote hx of MI or ACS and reduced ejection fraction
What is Labetalol used for?
Severe htn or treatment of hypertensive emergencies
What two types of drugs should be given to all patients (unless contraindicated) with left ventricular systolic dysfunction caused by MI to reduce their mortality?
- Carvedilol/Metoprolol/Bisoprolol (1 of these beta blockers)
- ACEI
Beta blockers should be given to all patients with symptomatic CHRF and LVEF <40% except in the case of…?
- Bronchospastic disease
- Symptomatic bradycardia or heart block
What are the contraindications to Beta blockers?
- Hypersensitivity to Carvedilol
- decompensated cardiac failure
- Bronchospastic disorders/asthma
- Cardiogenic shock
- Hepatic impairment
What are patients cautioned against abrupt withdrawal of Beta blockers?
- If the drug is abruptly stopped rather than gradually, patients with CAD run the risk of acute tachycardia, htn, or ischemia
What other diseases are exacerbated by Beta blockers?
- Vasospastic angina
- Bronchospastic disease
- DM
- HF
- Hepatic impairment
- Myasthenia gravis
- PAD
- Pheochromocytoma
- Psoriasis
- Thyorid disease
What is the MOA and effects of Ivabradine?
- Specific inhibition of hyperpolarization activated cyclic nucleotide gated channels within SA node
- Its effects are disrupting the funny Na current to prolong diastole and slow HR down
What is Ivabradine used for?
- Treatment of resting HR over 70 bpm in patients who are stable but have symptomatic LVHF <35% and cannot tolerate more beta blockers
What are the Contraindications of Ivabradine?
- Acute decompensated HF
- Hypotension
- Sick sinus syndrome/AV block
- Pacemaker
- Severe hepatic issues
- Strong CYP3A4 inhibitor use
what is the MOA of Spironolactone?
- Competitive antagonist of aldosterone receptors
Effects and uses of Spironolactone?
- K sparing diuretic
- Antagonizes profibrotic effect of aldosterone
- Used to:
- Counteract K loss induced by other Diuretics
- Reduce fibrosis in HFrEF and post MI heart failure
Toxicities of Spironolactone?
- Hyperkalemia
- amenorrhea, hirsutism, gynecomastia, impotence
- Tumorigen in chronic animal toxicity studies so avoid unnecessary use
What are common reasons to give diuretics?
- Essential Htn
- Edema associated with CHF, Liver failure, and Kidney failure
If a diuretic works upstream from the collecting duct what is it’s effect on K?
K losing
- Thiazides and loop diuretics
If a diuretic exerts effects in the collecting duct what happens with K?
- They are K sparing
- Spironolactone (aldosterone blocker)
- Triamterene and amiloride (Na channel blocker)
What is the effect of extracellular K on excitable tissues?
- If we are hyperpolarized (hypokalemic) we are too far from threshold to fire an AP
- If we are hyperkalemic we are more depolarized than normal and can be fired by “noise”
- Increase RMP to above threshold to where the cell can’t repolarize to fire a second time properly
H___kalemia increases the toxicity of digitalis in patients with CHF?
Hypokalemia
What are the effects of hyperkalemia on the heart?
- Tall T waves
- Prolonged PR
- Widened QRS
- Flattened P
- Bradycardia, ventricular tachy, or fibrillation
- Sinus arrest or nodal rhythm with asystole
Hypokalemia effect’s on heart?
- Flattened T waves
- ST segment depression
- Prolonged QT
- Tall U waves
- Atrial arrhythmia
- Vent tachy or V.fib
What do loop diuretics block?
- Na K and 2CL cotransporter blockers
- they are K losing
MOA of Furosemide and class?
- inhibits reabsorption of Na and Cl in thick ascending loop of henle blocking the NaK2Cl transporter
- Loop diuretic
Furosemide clinical uses?
- management of edema assoc. with
- HF
- Liver failure
- Renal failure
- Decreases preload and decreases ECV
- rapid dyspnea relief
- treats htn
- works in patients with low GFR unlike thiazides
Toxicities of furosemide?
- Hypokalemia
- Hyponatremia
- Hypocalcemia (Increased risk kidney stones)
- Hypomagnesemia
- Hypochloremic metabolic alkalosis
- Hyperglycemia
- Hyperuricemia
- Ototoxicity
- Sulfa drug so hypersensitivity risk
If you have a patient with a sulfa allergy, what loop diuretic can you give them?
Ethacrynic acid
What drugs do loop diuretics interact with?
- Digoxin
- Ototoxic drugs
- Potassium sparing diuretics
MOA for HCTZ?
- Inhibits sodiuim reabsorption in distal tubules by blocking NaCl transporter
- K losing
What is HCTZ used for?
- Hypertension
- not effective with low GFR
- treatment of edema
- Calcium nephrolithiasis off label
What vasodilators are used for Chronic HF?
- Isosorbide dinitrate to dilate veins and decrease preload
- Plus hydralazine to dilate arteries and decrease afterload
- Packaged as BiDil
- Useful for African Americans
Nitroglycerin effects and clinical uses?
- Vasodilator effect on veins and arteries
- used for angina pectoris
- acute decompensated HF especially when assoc with acute MI
Effects of hydralazine? Clinical uses for it?
- direct vasodilation of arterioles
- Moderate to severe hypertension
- off label for HFrEF and hypertensive emergency
Hydralazine AE’s?
- Angina pectoris
- Flushing
- Peripheral edema
- tachycardia
- Pruritis
- Drug induced lupus like syndrome
MOA of Digoxin? Effects?
- Na K ATPase inhibition
- Direct suppression of AV node conduction
- Increased contractility
- Positive inotropic effect, enhanced vagal tone and decreased ventricular rate to fast atrial arrhythmias
Pharmacokinetics of digoxin?
- crosses placenta but long hx of safe use in pregnant women with SVT
Digoxin non cardiac adverse effects?
- anorexia
- N/V
- salivation
- halos, yellowish or greenish tinge to objects
Digoxin drug interactions?
- Diuretics- these cause hypokalemia and that leads to increased digoxin binding leading to increased toxicity
- ACE inhibitors ARBS increase K levels decreasing digoxin effects
- Sympathomimetics
- Quinidine, spironolactone, varapamil,propafenone, and alprazolam
- Cholesterol binding resins
How does Digoxin impact the EKG?
- depression of ST segment and longer PR interval at therapeutic levels
- toxic levels you get AV dissociation (lacking QRS after every P)
- toxic levels also result in ectopic ventricular beats
In order to administer digoxin what must the heart rate be?
- “normal” cant be less than 60 bpm or toxicity can occur causing an AV block
How do you treat a digoxin OD?
- KCl
- Lidocaine (Na channel blocker)
- Phenytoin (Na channel blocker)
- Anti digitalis Ab’s (Digibind)
For patients who are classified into Stage A (ACCF/AHA) what medications are going to be used?
- ACEI or ARB in patients with vascular disease or DM
- Possibly statins
For patients who are classified into Stage B (ACCF/AHA) what medications are going to be used?
- ACEI or ARB
- Beta blockers if appropriate
- Potentially defibrillator or revasculartaion
For patients who are classified into Stage C (ACCF/AHA) what medications are going to be used?
- ACEI or ARB’s or ARNI with a beta blocker and aldosterone antagonist
Valsartan/Sacubitril should not be administered with what class?
ACEI as it increases bradykinin and increases risk of angioedema
What medications are tolerated better when patients are “dry”? (stage C)
Beta blockers, but only carvedilol, metoprolol, or bisoprolol
What medications are better tolerated when patients are “wet”? (stage C)
- ACEI/ARB/Angiotensin receptor neprilysin inhibitor (ARNI)
- ARNI are preferred
Once you have a beta blocker and angiotensin antagonist and still aren’t seeing results (stage C), what should you add?
aldosterone antagonist or a SGLT2 inhibitor
In an African American patient who is persistently symptomatic despite their therapies what should you consider?
- consider hydralazine and isosorbide dinitrate
- If resting HR is above 70 in sinus rhythm despite max beta blocker add ivabradine
For patients with HFrEF in stage D, what are additional therapy options that need to be considered?
- Palliative care
- Transplant
- LVAD
- Investigational study
In a patient with HFpEF, what drugs have NO evidence of improving the sx?
- nitrates
- PDE5 inhibitors
- Digoxin
For a patient with HFpEF what should the therapy be directed at?
- symptoms and the associated symptoms
- htn
- lung dz
- CAD
- a. fib
- obesity
- anemia
- DM
- Kidney dz
- sleep apnea
What do you give to a patient in ADHF?
More Diuretics
ADHF who is hypertensive, what do you give?
Loop diuretic + vasodilator
Hypotensive ADHF patient, what do you give them?
Loop diuretic
Drugs to avoid in patients with HF?
- Class 1 antiarrhythmics
- CCB
- NSAIDs
