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Phcol 402 > 01/26-27/16 > Flashcards

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
Angiotensin II receptor antagonists: Clnical Use in CHF
* 1st line therapy for CHF * less data available than ACE-I on CHF morbidity and mortality * use with diuretics
26
Angiotensin II receptor antagonists: toxicity
* severe hypotension * NO cough reflex * less angioedema * hyperkalemia * tertogenic
27
Thiazides
* **hydrochlorothiazide (Microzide)**
28
Thiazides: MOA
* inhibit apical Na+/Cl- transporter (NCC) in DCT
29
Thiazides: Toxicity
* hypokalemic metabolic alkalosis
30
Thiazides: Use in CHF
* 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
Loop Diuretics
* **Furosemide (Lasix)**
32
Loop Diuretics: MOA
* inhibit apical Na+/K+/2Cl- transporter (NKCC2) in TALOH
33
Loop Diuretics: Toxicity
* hypokalemic metabolic alkalosis
34
Loop Diuretics: Use in CHF
* 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
K+ sparing diuretics: aldosterone antagonists
* Eplerenone (Inspra) * **Spironolactone (Aldactone)** * Decrease efficacy compared to loop/thiazide * use with loop/thiazide diuretics to offset hypokalemia/hypomagnesemia
36
K+ sparing diuretics: aldosterone antagonists RALES trial
* Additive effects with ACE inhibitors * Increase survival in CHF patients independent of diuresis
37
K+ sparing diuretics: aldosterone antagonists Toxicity
* Hyperkalemia * gynecomastia (with spironolactone but not eplerenone) * ototoxicity (reversible) * metabolic alkalosis
38
Neprilysin Inhibitors
* Sacubitril and Valsartan combination therapy (Entresto)
39
Entresto: MOA
* Valsartan: ATII-1 receptor antagonist * Sacubitril: neprilysin inhibitor * enzyme that breaks down atrial/brain natriuritic factor * vasodilation * decreases preload/afterload * Decrease TPR
40
Entresto: Clincal use in CHF
* PARDIGM-HF study * superior to ACE-inhibitors to reduce risk of death in chronic heart failure patients with reduced ejection fraction
41
Entresto: toxicity
* angioedema * hypotension * long term effects?
42
Diagram of factors contributing to CHF
43
Acute Decompensated Heart Failure
* 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
Phosphodiesterase-3 Inhibitors
* **Amrinone (Inocor)** * Milrinone (Primacore) * Enoximone (Perfan)
45
Phosphodiesterase-3 Inhibitors: MOA
* Inhibit PDE III→increases cAMP→increases PKA activity * Cardiac: increase L-type Ca2+ channel opening→increase CO * Vascular: increases K+ channel opening→vasodilation
46
Phosphodiesterase-3 Inhibitors: Clinical use in CHF
* **IV** for acute decompensated heart failure * Increase HF morbidity and mortality * short duration of action (minutes)
47
Phosphodiesterase-3 Inhibitors: toxicity
* arrhythmia
48
Sympathomimetics
* 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
Vasodilators
* Nesiritide (Natrecor) * **Nitroprusside (Nitropress)** * **Isosorbide dinitrate/Hydralizine (BiDil)**
50
Vasodilators: MOA
* Increase NO in vascular smooth muscle * Vasodilation * Decrease preload/afterload * Decrease TPR
51
Vasodilators: Clinical Uses in CHF
* IV: Nesiritide or Nitroprusside for acute decompensated heart failure * Oral: isosorbide dinitrate/hydralazine for CHF patients unresponsive to diuretics/ACE-I/ARB
52
Vasodilators: Toxicity
* Reflex tachycardia * Hypotension * Headache/dizziness
53
Digoxin: Drug Card
* 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
Metoprolol: Drug Card
* 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
Carvedilol: Drug Card
* 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
Captopril: Drug Card
* 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
Losartan: Drug Card
* 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
Furosemide: Drug Card
* 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
Hydrochlorothiazide: Drug Card
* 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
Spironolactone: Drug Card
* 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
Amrinone: Drug Card
* 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
Dobutamine: Drug Card
* 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
Nitroprusside: Drug Card
* 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
Hydralazine+Isosorbide Dinitrate: Drug card
* 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

Phcol 402 (11 decks)

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