Drugs for Heart Failure Flashcards
Term for right-sided heart failure NOT due to left-sided heart failure, but caused by things like COPD, interstitial lung dz, pulm HTN, thromboembolic dz, OSA, etc.
Cor pulmonale
Type of heart failure in which the body’s need for cardiac output is abnormally elevated to a point beyond the heart’s capability
High-output heart failure
Causes of high-output heart failure
Hyperthyroid Pregnancy Anemia AV fistula Wet beriberi (thiamine def) Paget’s dz
2 types of left sided heart failure = systolic and diastolic. What is systolic left-sided heart failure?
Failure of the pump function of the heart (EF < 45%), typically d/t dysfunction or deestruction of cardiac myocytes or their molecular components
Usually progressive chamber dilation with eccentric remodeling
What is diastolic left-sided heart failure (DHF)?
Occurs when ventricular capacitance is diminished and/or when the ventricle becomes “stiff” and cannot fully reslax during diastole; abnormal diastolic function usually with concentric remodeling or hypertrophy
Dx is fairly common among older women; causes include ventricular hypertrophy d/t chronic HTN and CT diseases such as amyloidosis
~normal LVEF with ~normal EDV
Dx is one of exclusion — consider diastolic heart failure when there is heart failure with PRESERVED EF!
Complications of DHF
DHF —> poor tolerance of Afib d/t loss of atrial contraction and decreased ventricular filling
DHF —> poor tolerance of tachycardia d/t shorter duration of diastole — limits time for relaxation and filling
DHF is worsened by increased MAP, especially if abrupt or severe
Worsening of DHF by ischemia raises left atrial pressure —> angina, wheezing, SOB, pulmonary edema
Compensatory change in pts with heart failure in terms of preload and afterload
Increase in preload and afterload
Rationale for using ACE inhibitors/ARBs in heart failure
Decrease angiotensin II —> less vasoconstriction (decreased afterload), less aldosterone secretion and less sodium/water retention (decreased preload), decreased cell proliferation and remodeling
Note that high doses are required
Prototypical ACE inhibitor(s)
Captopril
[others include enalapril, benzapril, lisinopril]
Beware of cough and angioedema AEs
Prototypical ARBs
Losartan
[others include valsartan and candesartan]
T/F: ARBs induce a more complete inhibition of the RAAS system than the ACE inhibitors
True
But ACE inhibitors usually recommended as first choice
AEs of ARBs
Hypotension Fatigue Dizziness Fever Hypoglycemia Hyperkalemia Diarrhea Gastritis Nausea Weight gain Anemia Weakness Joint pain Cough, bronchitis, nasal congestion
[common with valsartan = hypotension, hyperkalemia, increased serum Cr]
ACE inhibitors or ARBs should be administered to ALL pts with LV systolic failure or LV dysfunction without heart failure EXCEPT in what circumstances?
Not tolerated (cough, angioedema — try ARB!)
Pregnant
Hypotensive
Serum Cr > 3 mg/dL
Hyperkalemia
What effect does heart failure have on the autonomic nervous system?
Increases sympathetic activity —> increased HR, increased myocardial contractility, increased vascular resistance
Prototypical beta blockers used in heart failure
Metoprolol, bisoprolol, carvedilol
[research suggests carvedilol works best]
MOA of carvedilol
Nonselective beta and alpha blocker with no intrinsic sympathomimmetic activity
In CHF, decreases pulmonary capillary wedge pressure, pulmonary artery pressure, HR, systemic vascular resistance, right atrial pressure —> increased stroke volume index
Clinical applications of carvedilol in terms of heart failure
If clinically stable, carvedilol (or bisoprolol or metoprolol) is recommended for all with recent or remote hx of MI or ACS and reduced EF (<40%), or just those with reduced EF to prevent symptomatic heart failure
Used to prevent down-regulation of the beta1 adrenergic receptors in the heart as aresult of excess sympathetic stim during heart failure — keeps heart responsive to sympathetic drive, protects against dysrhyhtmias, reduces renin secretion, reduces myocardial O2 consumption, limits heart remodeling and reduces necrosis and apoptosis of myocardial cells
[NOTE should only be administered to clinically stable pts]
Toxicities associated with carvedilol
Allergy Angina Dizziness Lightheadedness Fainting Generalized swelling Pain SOB Bradycardia Weight gain Angina/MI if abruptly stopped
Unless there are contraindications, carvedilol should also be given along with ______ to all pts with left ventricular systolic dysfunction caused by MI to reduce mortality
ACE-I
MOA of ivabradine
Selective and specific inhibition of the HCN channels (f-channels) within the SA node of cardiac tissue
Disrupts “funny” current to prolong diastole and slow HR
Clinical use of ivabradine
Tx of resting HR >70 bpm in pts with stable, symptomatic CHF wtih left ventricular EF <35% who are in sinus rhythm with:
- Maximally tolerated doses of beta blockers (or)
- Contraindications to beta-blocker use
AEs of ivabradine
Bradycardia HTN Increases risk of afib Heart block Sinoatrial arrest
MOA of spironolactone
Competitive antagonist of aldosterone receptors, decreases aldosterone-stimulated gene expression
Clinical use of spironolactone in heart failure
Decreases myocardial fibrosis
Reduces early morning rise in HR
Reduces mortality and morbidity in pts with severe heart failure
[other range of benefits includes decreased Na and water retention, decreased K+ and Mg loss, prevents reduction of baroreceptor reflex, decreases ischmia, decreases sympathetic activation]
AEs of spironolactone
Hyperkalemia Amenorrhea Hirsutism Gynecomastia Impotence Tumorigenic
Spironolactone and eplerenone are approved for tx of symptomatic heart failure with reduced systolic function, but are the most underutilized of all classes, primarily because of potential complication of _______
Hyperkalemia
MOA of furosemide
Blocks Na/K/2Cl cotransporter
Indirectly inhibits paracellular reabsorption of Ca and Mg by TAL d/t loss of K backleak responsible for lumen + transepithelial potential
Causes increased excretion of water, sodium, potassium, chloride, magnesium, and calcium
Clinical use of furosemide (or torsemide, bumetanide, ethacrynic acid) in heart failure
Management of edema associated with heart failure
Decreases preload —> treats acute pulmonary edema; rapid dyspnea relief
Toxicities of furosemide
Hypokalemia Hyponatremia Hypocalcemia Hypomagnesemia Hypochloremic met.alkalosis Hyperglycemia Hyperuricemia Increased cholesterol and TAGs
Ototoxicity
Sulfonamide — so risk of hypersensitivity
MOA of HCTZ
Inhibits Na reabsorption in DT via blockade of NaCl cotransporter
Increases urinary excretion of Na, H2O, K, and Mg
Clinical use of HCTZ (or other thiazides - chlorothiazide, chlothalidone, metolazone) in heart failure
Relief of congestion — gets rid of excess volume and returns ventricular fiber length to more optimal range
Note that LOOP diuretics are used first, K+ sparing diuretics next, and if STILL needing more diuresis, thiazides are used
Toxicities of thiazides
Orthostatic hypotension Hypokalemia Hypomagnesemia Hyponatremia Hypochloremic metabolic alkalosis Hypercalcemia Hyperglycemia Hyperuricemia
Sulfonamide— so risk of hypersensitivity
Vasodilators used for chronic HF
Isosorbide dinitrate (to dilate veins, decrease preload) + Hydralazine (to dilate arteries, decrease afterload)
The combination of vasodilators isosorbide dinitrate + hydralazine is especially useful in _____ ____, caucasians fail to respond for unknown reasons. It is also a good drug to consider in pts who cannot tolerate ______
African Americans; ACE-I
MOA of nitroglycerin
Forms free radical with NO, which increases cGMP —> smooth muscle relaxation
Produces vasodilation in peripheral veins and arteries (more potent in veins)
Primarily reduces cardiac O2 demand by reducing preload, may modestly reduce afterload, dilates coronary arteries
Clinical applications of nitroglycerin in terms of heart failure
Tx or prevention of angina pectoris
Acute decompensated heart failure (especially when associated with AMI)
Toxicities associated with nitroglycerin
Reflex tachycardia, flushing, hypotension, orthostatic hypotension, peripheral edema, syncope, bradycardia
HA, dizziness, light headedness, N/V, xerostomia, paresthesia, weakness, dyspnea, pharyngitis, rhinitis, diaphoresis
MOA of hydralazine
Not completely understood
Endothelium dependent, hyperpolarizes, requires activation of COX, mediated by PGI2 receptor
Effect is direct vasodilation of arterioles with little effect on veins —> decreased systemic resistance
Clinical application of hydralazine in terms of heart failure
Used off-label for:
- HF with reduced EF if intolerance to ACEI or ARB
- HF with reduced EF class III-IV
Toxicities associated w/ hydralazine
Angina pectoris, flushing, orthostatic hypotension, palpitations, peripheral edema, tachycardia
Pruritis
Drug-induced lupus-like syndrome
[Tons more]
MOA of digoxin
Inhibition of Na/K ATPase pump in myocardial cells
Results in increased contractility, direct suppression of AV node conduction, positive inotropic effect, enhanced vagal tone, and decreased ventricular rate to fast atrial arrhythmias
Clinical applications of digoxin
Control of ventricular response rate in adults with chronic afib
Tx of heart failure in adults and pediatrics to increase myocardial contractility
Used in pts with left ventricular systolic heart failure in combo with diuretics, beta-blockers, and ACEI
Especially useful in pts with afib d/t prolongation of effective refractory period at AV node
Digoxin is administered _______; its half life is 36-48 hr, but this is increased as CO and renal function decrease, so needs a ______ dose; it is widely distributed and crosses the placenta but it has long hx of being safe in pregnant women with _______
Orally; loading; SVT
Toxicities associated with digoxin
Accelerated junctional rhythm, asystole, atrial tachycardia with or without block, AV dissociation, heart block, PR prolongation, PVCs, ST depression, Vtach, Vfib
Dizziness, mental disturbance, HA, apathy, anxiety, confusion, delirium, depression, fever, hallucinations
Rash, N/V, diarrhea, abd pain, anorexia, weakness, blurred or yellow vision, laryngeal edema
Digoxin has positive inotropic effect on heart, what does this mean?
Increases force of ventricular contraction
Hemodynamic benefits of digoxin
Increased cardiac output —> decreased sympathetic tone, increased urine production, decreased renin release
Electrical effects of digoxin
Increases firing rate of vagal fibers, alters electrical properties of the heart — increases responsiveness of SA node to ACh
Effects of digoxin on ECG
At therapeutic levels: depression of ST segment, longer PR interval
Toxicity: AV dissociation, ectopic ventricular beats
Drug interactions with digoxin
Diuretics —- bc diuretics cause hypokalemia which leads to increased digoxin binding, which leads to increased risk of toxicity
ACEI and ARBs can increase K levels, decreasing digoxin effects
Sympathomimmetics - beneficial interaction on contractility, detrimental effect on arrhythmias
Quinidine, spironolactone, verapamil, propafenone, and alprazolam interfere with clearance of digoxin
Cholesterol-binding resins block its absorption
Which drugs show no evidence of benefit for diastolic heart failure?
Nitrates
PDE5 inhibitors
Digoxin
Drugs used to tx acute decompensated heart failure (ADHF)
Diuretics (loop>K+sparing>thiazide)
Vasodilators: nitroprusside, nitroglycerin
Discontinue carvedilol or other beta blockers
MOA of nitroprusside
Forms free radical with NO, increases cGMP —> smooth muscle relaxation
Causes peripheral vasodilation by direct action on venous and arteriolar smooth muscle; reduces peripheral resistance
Increases CO by decreasing afterload
Clinical applications of nitroprusside
Management of hypertensive crisis
ADHF
Used for controlled hypotension to reduce bleeding during surgery
Toxicities associated with nitroprusside
Tachycardia, ECG changes, flushing, hypotension, palpitation, substernal distress, increased ICP
Apprehension, dizziness, HA, rash
Metabolic acidosis secondary to cyanide toxicity
[many others]
Drug approved for acute decompensated CHF, but not effective in chronic cases
Nesiritde
Inotropic agents
Catecholamines
PDE inhibitors
Cardiac glycosides
Examples of sympathomimetics used as inotropic agents
Dobutamine (synthetic catecholamine that selectively activates B1 and B2 adrenergic receptors)
Dopamine (catecholamine, activates B1, increases HR and contractility, also stimulates alpha receptors at higher doses)
Prototypical PDE inhibitor (type III)
Milrinone
Results in vasodilation and inotropic effects with little chronotropic activity
Clinical applications of milrinone
Inotropic therapy for pts unresponsive to other acute heart failure therapies (e.g., dobutamine)
Outpatient inotropic therapy for heart transplant candidates
Palliation of sx of end-stage HF not eligible for transplant
Perioperative support for heart transplant recipients
Toxicities of milrinone
Arrhythmia
Hypotension
Angina/CP
HA
Drugs to avoid in heart failure
Class I antiarrhythmics — some are negative inotropes; all can cause arrhythmias
Calcium channel blockers — directly suppress myocardial contractility
NSAIDs — impair renal salt and water excretion which can exacerbate HF
