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83 Cards in this Set
- Front
- Back
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CHF Mortality Rate at 5 years?
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50-65%
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Types of Pumping Anomalies in CHF?
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Diastolic
Systolic Both (most common) |
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The kicker with prognosis of CHF?
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NEGATIVE CARDIAC REMODELING
Progressive myocyte damage and death even when you improve the pumping |
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Possible causes of negative cardiac remodeling?
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Flood of catecholamines, angiotensin II, Aldosterone, etc
Myocardial Signal Pathways Metalloproteases (remodeling) Caspases (apoptotic) Free Radicals |
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Drugs to attenuate Negative Cardiac Remodeling?
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ACEI
Beta Blockers Aldosterone Antagonists |
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General Objectives of CHF Therapy?
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Decrease Ventricular Preload and Afterload
Decrease Negative Cardiac Remodeling |
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Metabolic Objectives of CHF Therapy?
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Improve Contractile Efficiency
Dec O2 consumption/slow HR |
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Reversible Causes of Cardiac Dysfunction leading to CHF?
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MI
Valvular Disease HTN Intracardiac/Intravascular Shunts Arrhythmias Endocrine Disorders Diet |
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Drug Categories for CHF Therapy?
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Diuretics
ACE Inhibitors ARBs Nitrovasodilators Beta Blockers Cardiac Glycosides Beta-Adrenergic/Dopaminergic Agonists PDE Inhibitors |
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Different Diuretics used for CHF?
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Furosemide
Spironolactone Eplerenone |
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Purpose of Diuretics in CHF?
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Relieve fluid retention/congestion
Decrease Preload |
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Major SE's of Diuretics in CHF?
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Hyponatremia
Hypokalemia Hypochloremic Metabolic Alkalosis |
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Why is spironolactone so good?
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Its a K-sparing diuretic
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MOA of Spironolactone?
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Aldosterone Antagonist
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What added benefit is there since spironolactone blocks aldosterone?
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It blocks negative cardiac remodeling
30% decrease in mortality for class III-IV patients |
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Spironolactone is good when combo'd w/?
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ACE-I or Beta Blockers
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Even though spironolactone is the number 1 K-sparing diuretic, who has less SE's and same efficacy?
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eplerenone
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Bad effects of Ang II in CHF?
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Vasoconstriction
Potentiates NE Release Na/H2O retention Negative Remodeling |
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key to administration of ACE-I?
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start w/ a low dose and titrate up...make sure the bradykinin doesn't go nuts
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But I can't handle an ACE-I...what other option do I have?
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AT1 Receptor Blocker (ARB)
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Why don't we want to block the AT2 receptors?
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They lead to vasodilation, renal NO and PGI2, and Na excretion
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Examples of Nitrovasodilators?
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Nitroglycerin
Sodium Nitroprusside Isosorbide Dinitrate |
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Actions of Nitrovasodilators
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Relax VSMC
Dec LV Filling Pressure Dilate Coronary Vessels |
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Systemic role of Nitrovasodilators?
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Limited Effects
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Issue w/ Nitro's other than nitroprusside?
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Tolerance
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Indications for Nitro's
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Relief of Cardiac Ischemia
Emergencies When ACE-I's/Beta-Blockers aren't appropriate Combo's |
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When is an Isosorbide dinitrate + Hydralazine combo indicated?
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African Americans
Dec Mortality by 43% (along w/ conventional therapy) Alternate in ACE-I resistant w/ renal failure |
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Actions of Hydralazine?
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Vasodilator
Inc Renal Blood Flow |
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Where does BNP come from/
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stretched ventricular cardiac myocytes
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How does knowledge of BNP lead to a drug therapy?
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Recombinant DNA Drug Prep of BNP
Fxns as vasodilator and induces natriuresis and diuresis |
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Mechanism of BNP?
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Elevates cGMP --> vaso-relaxation
Promotes Natriuresis and Diuresis Blocks fibrosis cardiac remodeling |
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Administration Requirements for BNP?
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IV infusion w/ loading dose
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Adverse Effect of BNP?
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Hypotension
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When is BNP contraindicated?
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Systolic BP < 90
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When/how do you administer Beta-Blockers in a CHF patient?
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After stabilizing them on ACE-I, oral dosing, start low and titrate up
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What is the preferred Beta-Blocker for CHF?
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Carvedilol
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What ejection fraction is Carvedilol recommended for??????
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< 35%
???? |
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Metabolism of Carvedilol?
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hepatic
P450 2D6, so watch out for genetic variations quinidine and fluoxetine inhibit 2D6 |
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Mechanism of Carvedilol?
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Blocks Beta 1's and 2's
Dec Intropy Slow HR/dec O2 consumption Attenuate Neg Remodeling Antioxidant Blocks Alpha-1's in vasculature (vasodilation) Inhibits Smooth Muscle mitogenesis Dec SNS activation/Dec Renin |
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Adverse Effects of Carvedilol?
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Cardiac Depression
CNS: sedation, insomnia, depression From Beta-2 blockade: screw w/ asthma, reactive airway, and caution w/ peripheral vascular disease/vasospastic disorders |
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How to reverse carvedilol OD?
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Glucagon
Isoproterenol |
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Administration Requirements for BNP?
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IV infusion w/ loading dose
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Adverse Effect of BNP?
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Hypotension
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When is BNP contraindicated?
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Systolic BP < 90
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When/how do you administer Beta-Blockers in a CHF patient?
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After stabilizing them on ACE-I, oral dosing, start low and titrate up
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What is the preferred Beta-Blocker for CHF?
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Carvedilol
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What ejection fraction is Carvedilol recommended for??????
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< 35%
???? |
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Metabolism of Carvedilol?
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hepatic
P450 2D6, so watch out for genetic variations quinidine and fluoxetine inhibit 2D6 |
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Mechanism of Carvedilol?
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Blocks Beta 1's and 2's
Dec Intropy Slow HR/dec O2 consumption Attenuate Neg Remodeling Antioxidant Blocks Alpha-1's in vasculature (vasodilation) Inhibits Smooth Muscle mitogenesis Dec SNS activation/Dec Renin |
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Adverse Effects of Carvedilol?
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Cardiac Depression
CNS: sedation, insomnia, depression From Beta-2 blockade: screw w/ asthma, reactive airway, and caution w/ peripheral vascular disease/vasospastic disorders |
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How to reverse carvedilol OD?
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Glucagon
Isoproterenol |
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Other Beta Blockers approved for CHF?
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Metoprolol
Bisoprolol |
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Selectivity of Metoprolol
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Beta-1 antagonist
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Indications for Cardiac Glycosides?
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CHF w/ A-Fib
CHF refractory to ACE-I/Beta Blockers |
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how do cardiac glycosides affect survival and sx's?
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No effect on survival
improves sx's |
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Administration of Cardiac Glycosides?
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Only Oral Inotrope (in US)
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#1 Cardiac Glycosides?
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Digoxin = Digitalis
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Mechanism of Cardiac Glycosides?
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Direct enhancement of cardiac contraction
Slow HR by activating vagal tone Inc CO/Dec O2 consumption So it slows the heart down, but makes it beat more powerfully |
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How do you base your Digoxin dosing? Why?
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Base the dose on Lean Body Mass
Due to Principal Reservoir in the skeletal muscle |
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Cascade of Cardiac Glycoside's Positive Inotropic Effect?
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1. Inhibit Na/K ATPase preventing Na exit and K entry-->
2. Inc intracellular Na and Inc intracellular charge--> 3. enhanced membrane depol--> 4. Dec Ca exit, which means more Ca to interact w/ contractile proteins |
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How do you reverse Digoxin toxicity?
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Elevating Extracellular K
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How do cardiac glycosides slow HR?
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Stimulate vagal nucleus in CNS
Enhance baroreceptor sensivity Ach release @ nerve endings |
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Effects of Cardiac Glycosides on SNS?
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inhibits reflex-induced SNS tone
High (toxic) doses increase SNS activity (bad) |
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Central Points of Digoxin?
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Useful for A-fib
Toxicity can cause arrhythmias |
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Cardiac Glycoside effects on SA node?
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Conduction slowed via vagal effects
Inc RP Inc APD |
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Cardiac Glycoside effects on Atria and AV node?
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Speed conduction through atria, which could be bad except they also slow conduction through A-V node (the kicker for why they're used for A-Fib)
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How do cardiac glycosides cause arrhythmias?
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at toxic doses, they cause release of catecholamines that affect atria and ventricles independently and randomly
SNS effects are independent of vagal PNS activity |
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Drug Interactions of Digoxin?
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Quinidine, Verapamil, Amiodarone dec renal clearance-->70-100% inc
Erythromycin can double digoxin absorption rate |
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Contraindications of Digoxin?
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Hypothyroidism
Renal Failure both --> inc digoxin levels |
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SE's of Digoxin?
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GI: anorexia, nausea, pain
Arrhythmia Delerium, Fatigue, Confusion, Visual (halos) Correctable usually w/ dose adjustment |
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How do you reverse life-threatening digoxin toxicity?
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-Stop Digoxin Rx
-Atropine for Sinus bradycardia and SA Arrest -Potassium for AV or Ventricular Automaticity -Lidocaine for Vent Arrhythmias -Digibind=antidote, Ab Fab fragments |
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What are the drugs used when all else fails and/or at the end?
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Beta-adrenergic/dopaminergic agonists
Dopamine Dobutamine PDE-Inhibitors |
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Role of Beta-adrenergic/dopaminergic agonists?
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Positive Inotropy via inc in cAMP
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Roles of Dopamine?
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Vasodilation
Inc Renal BF @ [low] Enhance Beta activation of heart @ [middle] Vasoconstriction @ [high] |
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Mech of Dobutamine?
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Mostly Beta-1 stimulus, but some Beta-2 =>positive inotropy
Blocks Alpha's => vasodilation |
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When do we use Dobutamine?
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When vasodilators, ACE-I, beta blockers, diuretics, and digoxin all fail
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Kickers to Dobutamine administration?
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gotta be IV in the hospital = dobutamine holiday
Weaning is difficult |
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Which type of PDE-I's do you use in CHF?
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Type III
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Mech of PDE-I type III?
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Elevate cAMP (by stopping its breakdown)--> positive inotrope, vasodilator
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Examples of PDE-I type III's?
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Milrinone
Inamrinone |
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When do you use PDE-I's?
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LAST RESORT CAUSE THEY LEAD TO MORE NEG. CARDIAC REMODELING
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Adverse Effects of PDE-I's?
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Intolerable SE's
Dec Platelets Inc Mortality (53%) |
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How is milrinone administered/
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Combo w/ other drugs
Loading dose required and then continuous IV infusion |
