Cardiovascular Critical Care I
| (2) | Esmolol has the shortest half-life (cleared by plasma esterases), and administration |
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rates commonly coincide with high volumes of fluid.
| (3) | Agents with combined α1-antagonism and nonselective β-antagonism will have |
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greater effects on blood pressure than their β1-specific antagonist counterparts.
| • | β1-specific antagonist examples: |
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| • | Esmolol (intravenous), metoprolol tartrate (oral/intravenous) |
| • | Agents with combined α1- and nonselective β-antagonism effects include: |
| • | Carvedilol (oral) – about 25:1 ratio of β:α1 receptor activity |
| • | Labetalol (intravenous) – about 7:1 ratio of β:α1 receptor activity |
| • | Labetalol (oral) – about 3:1 ratio of β:α1 receptor activity |
| (b) | Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) |
| (1) | Not recommended in patients with HFrEF because of potent negative inotropic effects |
| (2) | May be of limited use in patients on vasopressors and/or inotropes, but can be used |
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for atrial tachyarrhythmias
| (c) | Amiodarone |
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| (1) | Commonly used for both atrial and ventricular tachyarrhythmias |
| (2) | Demonstrated safety in patients with structural heart disease (HF) because of neutral |
effect on mortality
| (3) | Affects all phases of the action potential (sodium [Na], calcium [Ca], potassium [K] |
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channel and provides some α- and β-antagonism)
| (4) | Severe hypotension can occur with intravenous amiodarone because of the solvent |
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polysorbate 80 (Tween 80) used in some formulations. This transient hypotension
in patients with a pulse can be associated with rapid infusions, particularly of
undiluted drugs, and is best avoided by dilution and slower administration. However,
in pulseless patients, rapid intravenous administration of undiluted amiodarone is
commonly indicated.
| (5) | Among common agents used in the ICU, amiodarone has one of the largest volumes |
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of distribution (about 60 L/kg) and prolonged half-lives (about 35–110 days).
| (6) | In adults, common total intravenous or oral loading doses throughout several days are |
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about 8–10 g before switching to a maintenance dose.
Loading dose = concentration × volume of distribution × weight
7.2–12 g = (1.5–2.5 mg/L) × (60 L/kg) × (80 kg)
| (7) | Extensive metabolism by CYP3A4 and CYP2C8 and enzyme inhibitor of CYP3A4, |
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CYP1A2, CYP2C9, and CYP2D6, resulting in several drug-drug interactions ((e.g.,
warfarin, statins)
| (8) | If patients are to be continued on amiodarone for a prolonged duration, thyroid and |
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liver function tests, pulmonary function tests, chest radiographs, and ophthalmic
examinations should be evaluated periodically (Heart Rhythm 2007;4:1250-9).
| (d) | Lidocaine |
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| (1) | Indicated only for treatment of ventricular tachyarrhythmias and is particularly useful |
if the tachyarrhythmia is caused by active ischemic myocardial tissue
| (2) | Efficacy and toxicity are both concentration dependent. |
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| (3) | Metabolism is largely dependent on hepatic blood flow; the primary metabolites are |
monoethylglycinexylidide (MEGX) and glycine xylidide (GX) and are mediated by
CYP1A2. Both lidocaine and MEGX contribute to therapeutic effect and toxicity,
whereas GX has predominantly toxic adverse effects. Lidocaine’s metabolites are
eliminated renally.