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What systemic parameter constitutes Heart Failure?
<45% Ejection Fraction
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What is Heart Failure in terms of Systole?
Failure of the pump function of the heart due to destruction of myocytes (EF <45%)
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What is Heart Failure in terms of Diastole?
Diminished Ventricular capatance (stiffening) due to ventricular hypertrophy or chronic hypertension
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What is Systolic Dysfunction?
Enlarged Ventricles that only pump out 40-50% of blood
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What is Diastolic Dysfunction?
Stiff ventricles fill with less blood than normal, about 60% is pumped out, but less blood than normal is in them
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What type of drugs would you use to treate Diastolic Failure?
ACEI, ARBs, Thiazide or Loop Diuretics, Spirolactone and BBs
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What type of drugs would you use to treat Systolic failure?
ACEIs, ARBs, Diuretics, Digitalis, Spirolactone or BBs
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What drug options are different between Systole and Diastole failure treatment options?
- Diastole: Thiazide of Loop Diuretics
- Systole: Digitalis, Diuretics not specified
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What characteristics does Ventricular remodeling have alter?
Alters shape, size and function, genes, molecules, cells and interstitium
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During ventricular modeling, Dilation can occur, what is this?
Myocyte lengthening and cell slippage
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Can cell loss occur in Ventricular remodeling?
Yes
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Would you expect Hypertrophy and interstitial fibrosis with Ventricular remodeling?
Yes
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What is Concentric Hypertrophy of the ventricle?
Congestion of the ventricle, wall thickening
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What is Eccentric Hypertrophy of the ventricle?
Thinning of the wall
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In heart failure there is a decrease in CO, compensation mechanism cause what changes?
Sympathetic discharge, Renin/Angiotensin/Aldosterone activation, fluid retention, ↑ preload/afterload, ↑ deleterious structural remodeling
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Compensation mechanisms for reduced Cardiac output due to heart failure have what effect on the overall well-being of the system?
Negative
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What are the goals of Treatment for Heart Failure?
1.) Treat the precipitating Factors 2.) Prevent Deterioration of Cardiac Function 3.) Control CHF state
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What drugs can help control CHF state?
Diuretics and digoxin
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What drugs prevent deterioration of Cardiac Function in Heart Failure?
ACEIs, ARBs, BB, Spirolactone and Vasodilators
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What reaction does Renin catalyze?
Conversion of angiotensinogen to angiotensin
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What reaction does Angiotensin converting enzyme catalyze?
Angiotensin I to Angiotensin II
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What are physiological ramifications of Angiotensin II?
Peripheral vasoconstriction, ↑BP, ↑ Extracellular volume, ↑ Aldosterone secretion, cardiovascular remodeling
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Less Angiotensin leads to what physiological changes?
Les vasoconstriction, aldosterone and cell proliferation/remodeling
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ACE inhibitors are the major drugs for the treatment of heart failure?
True
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What is the MOA of ACEIs?
Inhibit angiotensin II formation
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Enalapril is an active or prodrug?
Prodrug
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How do you identify an ACE inhibitor by name?
ending –pril
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Who should receive ACE inhibitors for heart failure?
Pregnant, hypotensive, kidney function <1/3, hyperkalemia or not tolerated
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What would be common signals that ACEI is not being tolerated by the patient?
Angioedema or cough
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What patient should receive ACE inhibitors for Heart Failure?
LV systolic failure or LV dysfunction w/o heart failure
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How can you identify the Angiotensin receptor blockers by name?
ending –sartan
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How do ARBs compare to ACEIs?
Similar effects, but ARBs: have lower bradykinin side effects, directly block receptors and less clinical information
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Would you give and ARB or ACEI to a pregnant patient?
Neither
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What can you replace ACEIs with if they are not tolerated?
ARB
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How can you identify a BB by name?
ending –olol or –lol
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How do BB treat heart failure?
Prevent down regulation of B adrenergic receptors in the heart as a result of sympathetic stimulation
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Do BBs prevent against arrhythmias?
Yes
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Do BBs inhibit the sympathetic responsiveness of the heart?
No, maintains the sympathetic responsiveness
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Do BBs enhance Renin Secretion?
No, reduce
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Do BBs reduce myocardial oxygen consumption?
Yes
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Do BBs limit heart muscle remodeling and aptoptosis?
Yes
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(True/False) Beta blockers can be administered to clinically unstable patients.
False, should only be administered to clinically stable patients
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What are the adverse effects of BBs?
Bradycardia, Withdrawal, Hypoglycemia in diabetes, Bronchospasm in asthma, CNS effects
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Patients with symptomatic CHF and low LVEF are good candidate for BBs, unless they have what compounding issues?
Bronchospastic disease, Symptomatic bradycardia or Heart Block
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B-blockers are used in patients with ____________systolic dysfunction caused by myocardial infarction to reduce mortality.
left ventricular
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Locally produced _____________ leads to cardiac fibrosis.
Aldosterone
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What beneficial effects do Spirolactone and Eplerenone have on the heart?
↓ Myocardial fibrosis, ↓ Mortality due to heart failure
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What are the adverse effect of Spirolactone and Eplerenone?
Hyperkalemia, Spirolacton: gynecomastia, hirsutism, menstrual irregularities
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Does Eplerenone cause gynecomastia?
Very little compared to Spirolactone
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What are the clinical uses for Spirolactone and Eplerenone?
Symptomatic Heart Failure with reduced Systole function
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What general positive effects would you expect Spirolactone and Eplerenone to have?
Cardioprotective and antiarrhythmatic, reduce morbidity and mortality
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Spirolactone and Eplerenone are well used for Heart Failure (True/False)
False, underused
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What vasodilators are used to treat Heart Failure?
Isosorbide dinitrate/hydralazine
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What is the trade name for Isosorbide dinitrate/hydralazine?
BiDil
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What is the physiological effect of Isosorbide Dinitrate?
Dilate veins and decrease preload
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What is the physiological effect of Hydralazine?
Dilates arteries, decreases afterload
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Why are isosrbide dinitrate and hydralazine beneficial together?
Isosorbide dinitrate decreases preload, while Hydralazine decreases afterload
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Can Diuretics be used in combination with eachother?
Yes
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How does Matolazone compare to Hydrochlorothiazide?
Longer half-life and more potent
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Which type of diuretics are most used in Heart Filure?
Loop diuretics
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What are the adverse effect of Loop diuretics when used for Heart Failure?
Hypokalemia, Hypomagnesemia, Hypotension
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Would you expect a rapid or slow improvement in symptoms with Loop diuretics?
Rapid
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(True/False)Loop diuretics have been shown to reduce admission for worsening heart failure.
True
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Spirolactone and Eplerenone cause a small or large decrease in Na and water retention?
Small
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What effect do loop diuretics have in ventricular remodeling?
Reduce
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Which Heart Failure treatment is a Cardiac Glycoside?
Digitalis
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Digitalis has profound effects on what properties of the heart?
Mechanical and electrical properties
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What effect does Digitalis have on Myocardial contractility of the heart?
Increases (positive inotropic effects)
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What is the major adverse effect of Digitalis?
Severe arrhythmias
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Is Digoxin a first line drug for Heart failure?
No
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What is the MOA for Digoxin?
Inhibitions of Na/K ATPase, leading to increased intracellular Ca and contractility
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Digoxin directly interacts with Ca receptors to increases Ca in the cell?
False, interacts with Na/K ATPase to increase gradient for Ca exchange into the cell
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What is the major therapeutic outcome of Digoxin use?
Increases the force of ventricular contractions
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When Digoxin binds the Na/K ATPase on the heart, it binds in place of which ion?
K
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What effect does too little K present have on Digoxin, Increased blockage, leading to toxicity
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What are the Hemodynamic effects of Digoxin?
- ↑ CO due to: ↓ sympathetic tone, ↓ Renin release ↑
- Urine production
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What electrical effects does Digoxin have?
↑ firing rate of vagal fibers, ↑ SA responsiveness to ACH, slows HR, effects impulse conduction in AV and perkinje fibers
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What ECG effect would you expect during Digoxin toxicity?
P wave without QRST
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At therapeutic levels of Digoxin, what ECG changes would you expect?
Depression of ST segment and longer PR interval
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What are the Cardiac adverse effects of Digoxin?
Bradycardia and abnormal impule conduction
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What are the Non-Cardiac adverse effects of Digoxin?
Anorexia, N and V, Salivation, excessive urination, Fatigue, Visual disturbances (blurred vision, halos, yellow/green tint to things)
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Does Digoxin have a wide or narrow therapeutic window?
Narrow
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Why is absorption inconsistent for Digoxin?
Variable dissolution rate of oral formulation, effected by disease states
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What effect do drugs that cause Hypokalemia have on Digoxin?
Increase binding and toxicity
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ACE inhibitors have what effect on Digoxin?
Decrease binding due to hyperkalemia
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How is Digoxin eliminated?
Mainly renaly
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Which drug classes used in the treatment of Heart Failure Reduce preload and afterload?
Loop Diuretics and Vasodilators
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Which drug classes used in the treatment of Heart Failure Reduce fluid volume?
Loop Diuretics
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Which drug classes used in the treatment of Heart Failure Reduce synthesis of angiotensin II?
ACE inhibitors
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Which drug classes used in the treatment of Heart Failure Prevent Remodeling?
ACE inhibitors, Angiotensin II receptor Blockers and B-Blockers
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Which drug classes used in the treatment of Heart Failure Prevent Arrhythmias?
B-Blockers
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Which drug classes used in the treatment of Heart Failure have Cardiotonic properties?
Digitalis
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Which drug classes used in the treatment of Heart Failure Have a sympathetic effect?
B-blockers
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Which drug classes used in the treatment of Heart Failure Reduce synthesis of Angiotensin II?
ACE inhibitors
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Inotropic agents other than Digitalis are used for what situation in Heart Failure?
Short term-Rescue
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What are the Sympathomimetic Inotropic agents?
Dobutamine and Dopamine
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What is the MOA for Dobutamine?
Selectively activates B1 receptors
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Which drug is usually preferred and why, dopamine or dobutamine?
Dobutamine, because it is B1 selective
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Describe the makeup of Dobutamine?
Synthetic catecholamine
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What is the MOA of dopamine?
Activates B1 receptors, increasing rate and contractility (Can also activate a1, causing NOR release and ↑ BP)
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What are the inotropic phosphodiesterase inhibitors used for the treatment of Heart Failure?
Inamrinone and Milrinone
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What is the MOA of Phosphodiesterase inhibitors?
Block degradation of cAMP, increasing cardiac contractility and vasodilation
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What route of administration are phosphodiesterase inhibitors given?
IV
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Are Phosphodiesterase inhiitors a safe and well tolerated treatment for Heart Failure?
No, numerous significant adverse effects, shown to decrease survival
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What vasodilators can you use for short term rescue therapy of Heart Failure?
Nesiritide, Nitroglycerin, Sodium Nitroprusside
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What is the makeup of Nesiritide?
Synthetic B-natriuretic peptide
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By what route is Nesititide given?
IV
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What situations would prompt you to give Nesiritide for Heart Failure?
Decompensated Heart Failure and Dyspnea due to HF
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What is the MOA for Nesiritide?
Stimulates guanyl cyclase receptor, increasing cGMP formation, suppresses Renin-Angiotensin system
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What effect does Nesiritide have on preload and afterload?
Decreases both
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What is the physiological effect of giving Nesiritide?
Vasodilation
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What are the major adverse effects of Nitroglycerin?
Hypotension and Reflex Tachycardia
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What is the MOA of Nitroglycerin?
Converted into NO
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What is the MOA of Sodium nitroprusside?
Converted into NO
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What are the major adverse effects of Sodium Nitroprusside?
Profound Hypotension and reflex tachycardia
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Sodium Nitroprusside is what class of drug?
Vasodilator
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Nitroglycerin is what class of drug?
Vasodilator
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Which acute treatment drugs used for Heart failure reduce preload and afterload?
Phosphodiesterase inhibitors, Nesiritide, Nitroglycerin and Sodium nitroprusside
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What drugs used for Acute Heart Failure have direct Cardiotonic effects?
Dobutamine, Dopamine and Phosphodiesterase inhibitos
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Describe Heart Failure Stage A:
High risk for HF without structural change sor symptoms
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Describe Heart Failure Stage B:
Structural heart disease w/o symptoms or signs
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Describe Heart Failure Stage C:
Structural heart disease with prior or current symptoms
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Describe Heart Failure Stage D:
Refractory HF requiring specialized interventions
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What drugs might be used in a person with Stage A Heart Failure?
ACEI or ARB
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What drugs might be used in a person with Stage B Heart Failure?
ACEI, ARBs, B-blockers
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What drugs might be used in a person with Stage C Heart Failure?
ACEI, Diuretics, ARBs, Digitalis, Hydralazine/Nitrates
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What drugs might be used in a person with Stage D Heart Failure?
Usually more extreme measures are used for Stage D, like heart transplant
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