12) Heart Failure Flashcards
Ejection fraction
- Percentage of blood leaving your heart each time it contracts
- Contraction = eject blood ventricles
- Relaxation = ventricles refill with blood
Stroke volume
- Volume of blood pumped from the left ventricle per beat
Cardiac output
- Volume of blood being pumped by the heart (by L/R ventricle) per unit time
Preload
- What comes before/into the heart by veins
- Venous return to the heart
Venodilator drugs effect on preload
- Reduce preload
Afterload
- What comes after the heart
- Pressure and resistance for the outflow from heart via arteries
Arteriodilator drugs effect on afterload
- Reduce afterload
Drugs that serve as both venodilators and arteriodilators will reduce both
- Preload
- Afterload
Systolic heart failure
- Reduction of cardiac contractile force and ejection fraction
- Heart failure with reduced ejection fraction (HFrEF)
Diastolic heart failure
- Stiffening or other changes in the ventricles that prevent adequate filling during diastole
- Ejection volume (stroke volume) is reduced but ejection fraction is normal
- Heart failure with preserved ejection fraction (HFpEF)
Heart failure is a combination of
- Systolic and diastolic dysfunction
The severity of heart failure is traditionally indicated on the New York Heart Association (NYHA) scale…based on symptoms
- Step I = symptoms occur only with maximal exercise
- Steps II and III = symptoms that occur with marked (II) or mild (III) exercise
- Step IV = symptoms are present at rest
Heart failure results when
- Cardiac output is inadequate for the needs of the body
A poorly understood defect in cardiac contractility is complicated by
- Multiple compensatory processes that further weaken the failing heart
Compensatory responses in heart failure
- Baroreceptor response
- RAAS activation, decreased GFR
- Increased ventricular wall tension
Baroreceptor response in heart failure
- SNS activation
- Increase in HR and contractility
RAAS activation and decreased GFR in heart failure
- Fluid retention
- Increased preload
Increased ventricular wall tension in heart failure
- Myocyte growth
- Hypertrophy
All bodily compensatory responses in heart failure lead to
- Increased cardiac output
3 major groups of drugs utilized in congestive heart failure (CHF)
- Positive inotropic drugs
- Vasodilators
- Miscellaneous drugs for chronic failure
Positive inotropic drugs for CHF
- Cardiac glycosides (digoxin)
- Beta agonists (dobutamine)
- PDE inhibitors (milrinone)
Vasodilators used for CHF
- PDE inhibitors (milrinone)
- Nitroprusside, nitrates, hydralazine
- Loop diuretics, angiotensin inhibitors, nesiritide, sacubitril, SGLT2 inhibitors
Miscellaneous drugs used for CHF
- Loop diuretics, angiotensin inhibitors, nesiritide, sacubitril, SGLT2 inhibitors
- Beta blockers, spironolactone
Pharmacologic therapies for heart failure
- Reduce Na/H2O retention (diuretics)
- Reduce afterload/Na/H2Ocretention (ACEI)
- Reduce sympathetic stimulation (β blockers)
- Reduce of pre/afterload (vasodilators)
Pharmacologic therapy in systolic failure includes
- Direct augmentation of depressed cardiac contractility with positive inotropic drugs (such as digitalis glycosides)
Prototypes and pharmacokinetics of cardiac glycosides (often called digitalis)
- Several come from the digitalis (foxglove) plant
- Prototype = Digoxin
- Digoxin has an oral bioavailability of 60–75%, and a half-life of 36–40 h
Cardiac glycoside mechanism of action
- Inhibition of heart Na+/K+ ATPase
- Small increase in intracellular sodium alters the driving force for Na/Ca exchange
- Less calcium is removed from the cell
- More Ca then stored in the sarcoplasmic reticulum and increases contractile force when released
Cardiac glycoside effects/usage
- Increase in contractility
- Used in heart failure and atrial fibrillation
Major signs of digitalis toxicity
- Arrhythmias, nausea, vomiting, and diarrhea
- Rarely, confusion or hallucinations and visual or endocrine aberrations may occur
Treatment for digitalis toxicity
- Correction of potassium and magnesium deficiency
- Anti-arrythmic
- Digoxin antibodies (Digibind)
Digitalis drug interactions
- Arrhythmogenesis is increased by hypokalemia, hypomagnesemia, and hypercalcemia
- Loop diuretics and thiazides may significantly reduce serum potassium and thus precipitate digitalis toxicity
Hypokalemia, hypomagnesemia and hypercalcemia potentiate
- Digitalis toxicity
Therapeutic index for digoxin
- 0.5 to 0.8/0.9 ng/mL
Rapid IV Ca2+ potentiates
- Arrhythmias
Digoxin metabolism
- P-glycoprotein (Pgp)
Digoxin GI interactions
- Antibiotics may wipe flora off (a route of digoxin metabolism)
Entresto is a combination of
- ARB (valsartan) and NI (sacubitril)
MOA of sacubitril
- Inhibits the enzyme neprilysin that degrades natriuretic peptides (NP) and bradykinin
Three molecules mediate the natriuretic peptide (NP) effects
- Atrial natriuretic peptide (ANP) secreted from the cardiac atria
- B-type natriuretic peptide (BNP) secreted from the cardiac
ventricles - CNP activates natriuretic peptide receptor (BNP-receptor)
All 3 NP effect mediators are broken down by
- Neprilysin
Natriuresis
- Excretion of sodium in urine
Diuresis
- Increased production of urine
Antifibrotic
- Prevent formation of fibrous connective tissue as a response to injury
Antiproliferative
- Heart growth inhibition
Antithrombotic
- Blood clotting inhibition
Entresto MOA/side effects
- Hypotension
- Hyperkalemia
- Increase serum creatinine
- Angioedema
- Decrease hematocrit and hemoglobin
- Cough (linked to increase bradykinin)
- Renal failure
Nesiritide (NP, vasodialator) mechanism of action
- Recombinant human B-type natriuretic peptide (BNP)
- Arterio- and veno-dilator by increasing cGMP in vascular smooth muscle
- Net effect: decrease BP, increase diuresis
- Promotes vasodilation, natriuresis, and diuresis
Nesiritide B-type NP characteristic
- Potent natriuretic peptide produced by ventricles
Nesiritide advantage
- Less arrhythmias (lack beta effects) vs. positive inotropes
- No tolerance
Nesiritide side effects
- Hypotension
- Azotemia
- Increase serum creatinine
- Headache
Nesiritide DOA
- 1 to several hours
Milrinone MOA
- Directly inhibits phosphodiesterase (PDE-3), increasing the effective concentration of cAMP
Milrinone clinical effect
- Positive inotropy (increase heart contractility)
- Decreased afterload
Milrinone side effects
- Thrombocytopenia
- Hypotension
- Arrhythmia
Dobutamine and dopamine are used in
- Systolic heart failure
- Some efficacy in acute HF (SE: arrhythmogenic)
Beta blockers (carvedilol, labetalol, and metoprolol) have shown
- Slower progression of chronic heart failure, especially in patients with hypertrophic cardiomyopathy
Dobutamine characteristics
- MOA = Beta 1 agonist
- Effect = increased contractility and cardiac output
Dobutamine side effects
- Hypertension
- Angina
- Tachycardia
- Arythmias
Low-dose dopamine
- 0.5-2 micro g/kg/min
- Direct stimulation of peripheral DA1 and DA2 receptors
Low-dose dopamine effects
- Induces intrarenal vasodilatation, augmented renal blood flow
Intermediate dose dopamine
- 3-10 micro g/kg/min
- Beta(1)-adrenergic receptor stimulation
Intermediate dose dopamine effects
- Increase contractility
High dose dopamine
- > 10 micro g/kg/min
- Alpha-adrenergic receptor stimulation
High dose dopamine effects
- Peripheral vasoconstriction
- Systemic vascular resistance
Loop diuretics and spironolactone effects
- Reduces preload and edema
- Vasodilating effect on pulmonary vessels
Loop diuretics action in HF
- Acute and chronic HF
Spironolactone action in HF
- Chronic heart failure
ACE inhibitor (anything ending in -il such as capropril) effects
- Blocks ACE
- Reduces Angiotensin II
- Decreases vascular tone and aldosterone secretion
Positive inotropes (names)
- Cardiac glycosides (digoxin)
- Sympathomimetics (dopamine, dobutamine)
Positive inotropes effects
- Increase cardiac contractility
Positive inotropes action in HF
- Cardiac glycosides (digoxin) = chronic HF
- Sympathomimetics (dopamine, dobutamine) = acute HF
Beta blockers (anything ending in -ol such as metoprolol) effects
- Decrease heart remodeling
Beta blockers action in HF
- Chronic HF
Vasodilators (names)
- Nitroprusside
- Hydralazine and isosorbide dinitrate
- Nesiritide (natriuretic peptide)
- Milrinone (phosphodiesterase inhibitors)
Nitroprusside effects
- Reduce preload and afterload
Nitroprusside action in HF
- Acute HF
Hydralazine and isosorbide dinitrate effects
- Poorly understood mechanism in HF
Hydralazine and isosorbide dinitrate action in HF
- Chronic HF in African Americans
Nesiritide (natriuretic peptide) effects
- Reduce preload and afterload
Nesiritide (natriuretic peptide) action in HF
- Acute HF
Milrinone (phosphodiesterase inhibitors) effects
- Increase contractility
Milrinone (phosphodiesterase inhibitors) action in HF
- Acute HF
Neprilysin inhibitor (with ARB) names
- Sacubitril/valsartan
Neprilysin inhibitor (with ARB) effects
- Increase BNP and ARB effects
- Reduce preload and afterload
Neprilysin inhibitor (with ARB) action in HF
- Chronic HF
Adrenergic blockers site of action in HF
- Decrease cardiac workload by slowing HR (b1) and decreasing BP (a1)
Direct vasodilators site of action in HF
- Decrease cardiac workload by dilating vessels and reducing preload
Phosphodiesterase inhibitors site of action in HF
- Increase cardiac output by increasing the force of myocardial contraction
ACE inhibitors site of action in HF
- Increase cardiac output by lowering BP and decreasing fluid volume
Diuretics site of action in HF
- Increase cardiac output by reducing fluid volume and decreasing BP
Cardiac glycosides site of action in HF
- Increase cardiac output by increasing the force of myocardial contraction
