01/26-27/16 Flashcards

1
Q

Congestive Heart Failure: Background

A
  • slow/progressive decline in cardiac output
  • heart unable to perfuse organs
  • acute decompensated heart failure
    • immediate treatment
  • ~5 million with CHF in USA
  • chronic disease: years to develop
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2
Q

Compensatory mechanisms in CHF

A
  • Increase SNS output
  • Increase RAAS activity
  • Increase plasma volume
  • Increase heart rate
  • Increase blood pressure
  • Increase cardiovascular remodeling
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3
Q

Frank-Starling curve in CHF patients

A
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4
Q

Spiral into CHF

A
  • Example of body making the situation worse
  • Release transmitters to increase BP, enothelin, angiotensin II
  • Increase afterload because constricts blood vessels. Makes heart have to work harder
  • Decreased ejection fraction. Less blood out of heart because hard to push blood out
  • Lots of other bad things happen from chronic NE and AT II release
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5
Q

Symptoms of CHF

A
  • shortness of breath
  • coughing/wheezing
  • edema
  • fatigue
  • lack of appetite, nausea
  • confusion
  • tachycardia/arrhythmia
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6
Q

CHF patient classification

A
  • Class I
    • no symptoms
  • Class II
    • mild symptoms
    • comfortable at rest
  • Class III
    • marked limitation in activity
    • only comfortable at rest
  • Class IV
    • severe activity limitations
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7
Q

Stages of Heart Failure and recommended intervention

A
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8
Q

Cardiac Glycosides

A
  • Digitoxin (Crystodigin)
  • Digoxin (Lanoxin)
  • isolated from digitalis species of herbaceous perennials
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9
Q

Cardiac Glycosides: MOA

A
  • inhibit Na+/K+ ATPase
    • Increase [Na+]i
    • Decrease Ca2+/Na+ exchange
    • Increase [Ca2+]i
  • Increase Ca2+ uptake into ER/SR by SERCA2 transporter
    • NCX activity depands upon Na+/K+ ATPase; because can’t go out of the NCX, more calcium intracellular. At the next heart beat, there is more calcium, makes a stronger contraction.
  • Increase inotropy (force of contraction)
    • Increase stroke volume
  • Increase PSNS activity
    • Decrease HR
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10
Q

Cardiac Glycosides: Electrical Effects

A
  • Increase intracellular Na+ and Ca2+
  • Increase resting membrane potential
  • oscillatory depolarizing afterpotentials
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11
Q

Cardiac Glycosides: Arrhythmias

A
  • Afterpotentials elicit action potentials in Purkinje fibers
    • bigeminy: one abnormal beat per cardiac cycle
  • Self-sustaining tachycardia
    • ventricular fibrillation
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12
Q

Cardiac Glycosides: Pharmacokinetics

A
  • 1 week for steady state levels to be reached
  • serum levels: TI=2
    • <0.9 ng/mL=safe
    • >2 ng/mL=toxic
      • use Digoxin antibody (Digibind) to find levels
  • duration 36-40 h
  • numerous DDI
  • excreted unmetabolized in urine, unless…
    • Eubacterium lentum: 10% of population
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13
Q

Symptoms of Cardiac Glycoside toxicity

A
  • CNS:
    • delirium, malaise, dizziness, abnormal dreams
  • Visual:
    • blurred vision, yellow halos
  • Cardiac:
    • atrial and ventricular arrhythmias, SA/AV node block
  • GI:
    • anorexia, nausea, vomiting, abdominal pain
  • Respiratory:
    • enhanced ventilatory response to hypoxia
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14
Q

Cardiac Glycoside: Clinical Use

A
  • Only oral ionotropic agent recommended for CHF
  • Increase quality of life/exercise tolerance
  • does not treat underlying disease progression
  • recommended for CHF with AFib
  • DIG trial:
    • 1997, ~6800 patients with Stage II-III CHF
    • ACE inhibitor + placebo or digoxin
    • Decrease risk of CHF mortality
    • Increase risk of arrhythmia mortality
    • net effect: no difference in mortalitly rates!
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15
Q

Beta-adrenergic receptor antagonists

A
  • Cardioselective (Beta1-ARs)
    • Metoprolol (Lopressor)
    • Bisoprolol (Zebeta)
  • Mixed selectivity (alpha1/beta1-ARs)
    • Carvedilol (Coreg)
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16
Q

Beta-adrenergic receptor antagonists: MOA

A
  • Antagonise cardiac beta1-ARs
    • decrease HR, decrease CO
    • decrease arrhythmias
    • decrease cardiac remodeling
  • Angatonize renal beta1-ARs
    • decrease renin release, decrease AT II/aldosteronse
    • decrease afterload, TPR
  • Carvedilol: antagonize vascular alpha1-ARs
    • decrease afterload, TPR
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17
Q

Beta-adrenergic receptor antagonists: Clinical Use in CHF

A
  • recommended for CHF II-III
  • use with ACE-inhibitor, diuretic
  • increase lifespan (probably because decrease odds of arrhythmia)
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18
Q

Beta-adrenergic receptor antagonists: toxicity

A
  • bradycardia
  • nausea
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19
Q

ACE-Inhibitors

A
  • Captopril (Capoten)
  • Enalapril (Vasotec)
  • Ramipril (Altace)
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20
Q

ACE-Inhibitors: MOA

A
  • Inhibit ACE
  • Decrease ATII production
  • Decrease aldosterone/VP→decrease plasma volume
  • Decrease afterload/total peripheral resistance
  • Decrease CVS remodeling
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21
Q

ACE-Inhibitors: Clinical Use in CHF

A
  • 1st line therapy for CHF
  • Decrease CHF mortalilty and morbidity
  • use with diuretics
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22
Q

ACE-Inhibitors: Toxicity

A
  • severe hypotension
  • cough reflex
  • angioedema
  • hyperkalemia
  • teratogenic
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23
Q

Angiotensin II receptor antagonists

A
  • Losartan (Cozaar)
  • Olmesartan (Benicar)
  • Telmisartan (Micardis)
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24
Q

Angiotensin II receptor antagonists: MOA

A
  • inhibit ATII type 1 receptor
    • type 2 work on endothelium; stimulating type 2, NO production and vasodilation; type 1 effects will win over type 2. These drugs are selective to type 1. AT-II still floating around body, but now can work on the type 2 receptors
    • No effect on ATII production
  • Decrease aldosterone/VP→decrease plasma volume
  • Decrease afterload/total peripheral resistance
  • Decrease CVS remodeling
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25
Q

Angiotensin II receptor antagonists: Clnical Use in CHF

A
  • 1st line therapy for CHF
  • less data available than ACE-I on CHF morbidity and mortality
  • use with diuretics
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26
Q

Angiotensin II receptor antagonists: toxicity

A
  • severe hypotension
  • NO cough reflex
  • less angioedema
  • hyperkalemia
  • tertogenic
27
Q

Thiazides

A
  • hydrochlorothiazide (Microzide)
28
Q

Thiazides: MOA

A
  • inhibit apical Na+/Cl- transporter (NCC) in DCT
29
Q

Thiazides: Toxicity

A
  • hypokalemic metabolic alkalosis
30
Q

Thiazides: Use in CHF

A
  • Initial therapy for CHF
    • Decrease SBP ~10-15 mmHg
    • Decrease afterload and preload
  • Ineffective with GFR <30 mL/min
  • Monitor serum electrolytes to prevent hypokalemia
  • Combine with K+ sparing diuretics, supplements
  • Diuretic resistance
  • Hypomagnesemia/hyperuricemia with long term use
31
Q

Loop Diuretics

A
  • Furosemide (Lasix)
32
Q

Loop Diuretics: MOA

A
  • inhibit apical Na+/K+/2Cl- transporter (NKCC2) in TALOH
33
Q

Loop Diuretics: Toxicity

A
  • hypokalemic metabolic alkalosis
34
Q

Loop Diuretics: Use in CHF

A
  • Oral for CHF
    • monitor serum electrolytes to prevent hypokalemia
  • IV for acute decompensated heart failure
  • Decrease peripheral/pulmonary edema
  • Increase dosage with renal impairment
  • Diuretic resistance
35
Q

K+ sparing diuretics: aldosterone antagonists

A
  • Eplerenone (Inspra)
  • Spironolactone (Aldactone)
  • Decrease efficacy compared to loop/thiazide
  • use with loop/thiazide diuretics to offset hypokalemia/hypomagnesemia
36
Q

K+ sparing diuretics: aldosterone antagonists

RALES trial

A
  • Additive effects with ACE inhibitors
  • Increase survival in CHF patients independent of diuresis
37
Q

K+ sparing diuretics: aldosterone antagonists

Toxicity

A
  • Hyperkalemia
  • gynecomastia (with spironolactone but not eplerenone)
  • ototoxicity (reversible)
  • metabolic alkalosis
38
Q

Neprilysin Inhibitors

A
  • Sacubitril and Valsartan combination therapy (Entresto)
39
Q

Entresto: MOA

A
  • Valsartan: ATII-1 receptor antagonist
  • Sacubitril: neprilysin inhibitor
    • enzyme that breaks down atrial/brain natriuritic factor
  • vasodilation
    • decreases preload/afterload
  • Decrease TPR
40
Q

Entresto: Clincal use in CHF

A
  • PARDIGM-HF study
    • superior to ACE-inhibitors to reduce risk of death in chronic heart failure patients with reduced ejection fraction
41
Q

Entresto: toxicity

A
  • angioedema
  • hypotension
  • long term effects?
42
Q

Diagram of factors contributing to CHF

A
43
Q

Acute Decompensated Heart Failure

A
  • most common indication for emergency care
  • >1 million admissions annually in USA
  • Common causes:
    • CHF, pneumonia, MI, arrhythmia, hypertension
  • Goals:
    • Increase CO
    • Increase oxygen delivery
44
Q

Phosphodiesterase-3 Inhibitors

A
  • Amrinone (Inocor)
  • Milrinone (Primacore)
  • Enoximone (Perfan)
45
Q

Phosphodiesterase-3 Inhibitors: MOA

A
  • Inhibit PDE III→increases cAMP→increases PKA activity
    • Cardiac: increase L-type Ca2+ channel opening→increase CO
    • Vascular: increases K+ channel opening→vasodilation
46
Q

Phosphodiesterase-3 Inhibitors: Clinical use in CHF

A
  • IV for acute decompensated heart failure
  • Increase HF morbidity and mortality
  • short duration of action (minutes)
47
Q

Phosphodiesterase-3 Inhibitors: toxicity

A
  • arrhythmia
48
Q

Sympathomimetics

A
  • Positive inotropic agents used during ADHF that mimic SNS
  • NE/EPI: rarely used
  • Dopamine:
    • <2ug/kg: stimulate VSMC D1/D2 autoreceptors
      • vasodilation
    • 2-5 ug/kg: stimulate cardiac beta1-ARs
      • increase cardiac output
    • 5-15 ug/kg: stimulate VSMC alpha1-ARs
      • vasoconstriction
  • Dobutamine
    • stimulate cardiac beta1-ARs
      • increase cardiac output
49
Q

Vasodilators

A
  • Nesiritide (Natrecor)
  • Nitroprusside (Nitropress)
  • Isosorbide dinitrate/Hydralizine (BiDil)
50
Q

Vasodilators: MOA

A
  • Increase NO in vascular smooth muscle
  • Vasodilation
  • Decrease preload/afterload
  • Decrease TPR
51
Q

Vasodilators: Clinical Uses in CHF

A
  • IV: Nesiritide or Nitroprusside for acute decompensated heart failure
  • Oral: isosorbide dinitrate/hydralazine for CHF patients unresponsive to diuretics/ACE-I/ARB
52
Q

Vasodilators: Toxicity

A
  • Reflex tachycardia
  • Hypotension
  • Headache/dizziness
53
Q

Digoxin: Drug Card

A
  • Brand Name:
    • Lanoxin
  • MOA:
    • Inhibit Na+/K+ ATPase
  • Clincal Uses:
    • CHF
    • arrhythmias
  • Toxicity:
    • Arrhythmogenic
    • Nausea, malaise, diarrhea
    • Vision problems
  • Extra Info:
    • Only approved cardiotonic agent for CHF
    • No net effect on CHF mortality
    • Low therapeutic index (~2)
54
Q

Metoprolol: Drug Card

A
  • Brand Name:
    • Lopressor
  • MOA:
    • selective beta-1 adrenergic receptor antagonist
  • Clinical Uses:
    • CHF
    • HTN
  • Toxicities:
    • Bradycardia, atroventricular block
    • CNS sedation
  • Extra Info:
    • Shown to reduce mortality in heart failure patients
    • widely used for Stage I/II hypertension
55
Q

Carvedilol: Drug Card

A
  • Brand Name:
    • Coreg
  • MOA:
    • mixed alpha-1 and beta-adrenergic receptor antagonist
  • Clinical Uses:
    • CHF
    • HTN
  • Toxicities:
    • Bradycardia, atrioventricular block
    • CNS sedation
    • less bronchospasm
  • Extra Info:
    • Composed of 4 stereoisomers
    • Shown to reduce mortality in heart failure patients
56
Q

Captopril: Drug Card

A
  • Brand Name:
    • Capoten
  • MOA:
    • Inhibit angiotensin-converting enzyme (ACE)
  • Clinical uses:
    • Stage I/II hypertension
    • CHF
    • diabetic renal disease
  • Toxicities
    • bradykinin cough reflex
    • hyperkalemia
    • teratogenic
  • Extra Info:
    • oral
    • effective up to 12 hours
57
Q

Losartan: Drug Card

A
  • Brand Name:
    • Cozaar
  • MOA:
    • Angiotensin-II type I receptor antagonist
  • Clinical Uses:
    • Stage I/II hypertension
    • CHF
  • Toxicities:
    • Hyperkalemia
    • Teratogenic
  • Extra Info:
    • Oral
    • No cough reflex
58
Q

Furosemide: Drug Card

A
  • Brand Name:
    • Lasix
  • MOA:
    • inhibit Na+/K+/2Cl- cotransporter (NKCC2) in thick ascending limb of Henle
  • Clincal Uses:
    • edema in CHF, cirrhosis, nephrotic syndrome
    • hypertension
    • hypercalcemia
  • Toxicities:
    • hypokalemia
    • ototoxicity
    • dehydration
  • Extra info:
    • “high ceiling diuretic”
    • rapid onset of action (minutes)
59
Q

Hydrochlorothiazide: Drug Card

A
  • Brand Name:
    • Microzide
  • MOA:
    • Inhibit Na+/Cl- co-transporter (NCC) in distal convoluted tubule
  • Clinical Uses:
    • HTN
    • CHF
    • idiopathic hypercalciuria
  • Toxicities:
    • hypokalemic metabolic alkalosis
    • hyponatremia
    • hyper-lipidemia, uricemia, calcemia
  • Extra info:
    • “low ceiling diuretic”
    • component of many combination therapies
60
Q

Spironolactone: Drug Card

A
  • Brand Name:
    • Aldactone
  • MOA:
    • competitive antagonist of aldosterone receptor
  • Clincal Uses:
    • hyperaldosteronism
    • CHF
    • HTN
  • Toxcities:
    • hyperkalemia
    • endrocrine effects (i.e. gynecomastia)
  • Extra info:
    • used in combination with loop or thiazides to prevent hypokalemia
    • eplerenone lacks anti-androgen effects
61
Q

Amrinone: Drug Card

A
  • Brand Name:
    • Inocor
  • MOA:
    • Phosphodiesterase-3 inhibitor
  • Clinical uses:
    • acute decompensated heart failure
  • Toxicities:
    • arrhythmia
  • Extra Info:
    • IV for acute decompensated heart failure
    • short duration (minutes)
62
Q

Dobutamine: Drug Card

A
  • Brand Name:
    • Dobutamine
  • MOA:
    • beta-1 adrenergic receptor agonist
  • Clinical uses:
    • Acute decompensated heart failure
  • Toxicities:
    • arrhythmia
  • Extra info:
    • IV for acute decompensated heart failure
    • short duration (minutes)
63
Q

Nitroprusside: Drug Card

A
  • Brand Name:
    • Nitropress
  • MOA:
    • nitrovasodilator; nitric oxide donor
  • Clinical Uses:
    • acute decompensated heart failure
  • Toxicities:
    • tachycardia
    • excessive hypotension
  • Extra Info:
    • IV for acute decompensated heart failure
    • short duration (min)
64
Q

Hydralazine+Isosorbide Dinitrate: Drug card

A
  • Brand Name:
    • Bidil
  • MOA:
    • Hydralazine: vascular K+ channel opener
    • ID: nitric oxide donor, nitrovasodilator
  • Clinical Uses:
    • CHF
    • angina
  • Toxicities
    • reflex tachycardia
    • excessive hypotension
    • headache
  • Extra Info:
    • oral, long duration of action