Download CH20 Page 1-2 - Pharmacotherapy

20-1
VENTRICULAR ARRHYTHMIA
Nyagon’s Parking Lot Accident. . . . . . . . . . . . . . . . . . Level III
Kwadwo Amankwa, PharmD, BCPS
A 55-year-old woman with a history of atherosclerotic heart disease,
cardiomyopathy, and metabolic imbalance is brought to the emergency department (ED) after a syncopal episode. She had recently
started taking erythromycin for upper respiratory symptoms. She
subsequently experiences another episode in the ED and is found
to be in torsades de pointes (TdP). Sinus rhythm is restored with
magnesium, and then she is admitted for further electrophysiology workup. The reader is asked to evaluate a patient’s risk of
drug-induced arrhythmia, weigh the therapeutic alternatives for
treatment of acute-onset TdP, and select the optimal drug regimen
for terminating the arrhythmia. The reader is asked to educate the
patient regarding the risk for potentially dangerous drug–drug
interactions, to prevent recurrence of TdP.
✓Erythromycin2,4: A macrolide antibiotic with numerous
reports of QTc prolongation and TdP. Erythromycin also
causes TdP by blocking the delayed rectifier potassium current. In addition, because erythromycin is metabolized by
the CYP450 3A4 system, coadministration of a CYP 3A4
inhibitor (eg, cimetidine, diltiazem, or grapefruit juice) with
erythromycin increases the patient’s exposure to the torsadogenic agent.5
Desired Outcome
2.What are the short-term goals of pharmacotherapy for this
patient?
• Rapid diagnosis of TdP and identification of predisposing factors and/or offending agent(s)
• Restoration of sinus rhythm quickly to prevent sudden death
• Removal of the offending agent
QUESTIONS
• Correction of metabolic predisposing factors
Problem Identification
1.a. What risk factors predisposed the patient to drug-induced
arrhythmia?
Nyagon had multiple risk factors predisposing her to QTc prolongation and TdP.1 These include the following:
• Female sex
• Structural heart disease (systolic heart failure, ejection fraction
[EF] 30%)
• Electrolyte abnormalities
hypomagnesemia)
(eg,
hypokalemia
and
• Diuretic use
• Multiple QTc-prolonging drugs (eg, erythromycin and
amiodarone)
1.b. What features of the patient’s electrocardiogram (ECG) are
characteristic of TdP?
• TdP on an ECG or a rhythm strip shows a polymorphic
ventricular tachycardia, with the QRS axis appearing to twist
around an imaginary baseline. This gives the rhythm a sine
wave pattern.
• Cycles of long–short pauses immediately precede the
arrhythmia.
1.c. Discuss pharmacologic and nonpharmacologic factors that
may have caused drug-induced TdP in this patient.
• Although the patient experienced a drug-induced arrhythmia,
there were several nonpharmacologic contributory factors. The
patient was hypokalemic (2.8 mEq/L) and hypomagnesemic
(1.2 mg/dL). This may in turn have been caused or exacerbated
by the recent doubling of Nyagon’s furosemide dose.
Therapeutic Alternatives5–7
3.a. What nonpharmacologic therapies may be useful for this
patient?
• Hemodynamically unstable patients should be treated with cardioversion immediately, with energy ranging from 100 to 360 J.
3.b.What pharmacotherapy options are available for acute
treatment of TdP?
• Magnesium sulfate, 2-g IV bolus administered over 5 minutes.
Doses may be repeated in 15-minute intervals up to 12 g.
Drug of choice due to its effectiveness for TdP.
• Magnesium sulfate, 2-g IV bolus, followed by a continuous
infusion at 0.5–1.0 g/hour (alternative dosing for magnesium
especially useful in recurrent TdP).
• Temporary transvenous overpacing at a rate of approximately
100 bpm (especially effective in TdP associated with bradycardia and is an option in hemodynamically stable patients who
have failed magnesium therapy).
• Isoproterenol, initial dose 2 mcg/min IV titrated to a heart rate
of 100 or greater than current TdP rate. Used in cases of torsades associated with acquired long QT syndrome, underlying
bradycardia, or as a bridge to cardiac pacing.
• Lidocaine, IV 1–1.5 mg/kg bolus (maximum of 3 mg/kg), and
then maintenance of 1–4 mg/min. Used successfully in a few
case reports. Reserve for when magnesium or pacing fails to
convert the patient.
• Phenytoin, IV 10–15 mg/kg infused at a rate of 25–50 mg/min.
Used successfully in a few case reports. Reserve for when magnesium or pacing fails to convert the patient.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Ventricular Arrhythmia
CASE SUMMARY
✓Amiodarone2,3: A class III antiarrhythmic that prolongs the
QTc interval by blocking the delayed rectifier potassium
current. It is seldom associated with TdP in the absence of
metabolic predisposing conditions or coadministration with
a torsadogenic agent.
CHAPTER 20
20
• Pharmacologic agents from a broad range of classes, including
antiarrhythmics, antipsychotics, and antimicrobials, have been
implicated in causing QTc prolongation and/or TdP.2 Druginduced TdP may occur as a result of toxicity from a single
agent or from a drug interaction that results in an increase
in the serum concentrations of the offending agent. Potential
causative agents in this patient’s case include the following:
20-2
Optimal Plan
SECTION 2
4.Design a pharmacotherapeutic plan for the treatment of acute
drug-induced TdP for this patient.
Cardiovascular Disorders
• Magnesium, IV bolus 2 g over 5 minutes. This therapy is chosen because magnesium is particularly effective for TdP and
is thus considered first line in therapy for hemodynamically
stable patients. Magnesium shortens the QTc interval and suppresses early after depolarizations. Because the patient’s TdP
was not associated with bradycardia, transvenous overpacing
and isoproterenol are not appropriate options. Lidocaine and
phenytoin were not chosen because they have been used in
only a few case reports and hence lack a strong evidence base
for efficacy compared with the other options. Direct current
(DC) cardioversion is appropriate only in hemodynamically
unstable patients.
• The patient presented hypokalemic and hypomagnesemic
and thus needs electrolyte replacement. The patient’s potassium should be replaced at a rate of 20 mEq/hour via central
line or 10 mEq/hour via peripheral line. Potassium levels
should be checked 2 hours after replacement and with the
next morning’s lab or based on institution-specific protocol. Each 20 mEq of potassium infused will be expected to
increase serum potassium by approximately 0.25 mEq/L.
Magnesium levels should be checked 2 hours after treatment
and with morning labs.
Outcome Evaluation
5.What monitoring parameters should be used to assess efficacy
and toxicity of treatment?
• Monitor the patient’s rhythm continuously using 12-lead
ECGs and a rhythm oscilloscope.
• Monitor electrolytes per local protocol. Maintain serum potassium and magnesium concentrations at >4.3 mEq/L for the
former and >2 mEq/L for the latter.
Patient Education
6.What medication counseling should be provided for the
patient to prevent recurrence?
• It is likely that this problem was caused by the addition of the
antibiotic erythromycin to your medication regimen. We have
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
corrected your potassium and your magnesium levels, which
were also low possibly due to your furosemide.
• In the future, when you go to the hospital or to the doctor’s
office for care, please bring a list with you of all medications,
vitamins, and herbals that you take. This will ensure all your
caregivers are aware of all your medications and should help
prevent the prescription of medications that should not be used
together.
REFERENCES
1. Gowda RM, Khan IA, Wilbur SL, Vasavada BC, Sacchi TJ. Torsades de
pointes: the clinical considerations. Int J Cardiol 2004;95:219–222.
2. Arizona CERT—Center for Education and Research on Therapeutics.
Available at: http://www.azcert.org/. Accessed May 1, 2013.
3. Yee GY, Camm AJ. Drug induced QT prolongation and torsades de
pointes. Heart 2003;89:1363–1372.
4. Owens RC, Nolin TD. Antimicrobial-associated QT interval prolongation: pointes of interest. Clin Infect Dis 2006;43:1603–1611.
5. Tisdale JT. Torsades de pointes. In: Tisdale JE, Miller DA, eds. DrugInduced Diseases: Prevention, Detection and Management. Bethesda,
MD, American Society of Health-Systems Pharmacists, 2010. p. 485–515.
6. European Heart Rhythm Association, Heart Rhythm Society, Zipes DP,
et al. ACC/AHA/ESC 2006 guidelines for management of patients with
ventricular arrhythmias and the prevention of sudden cardiac death: a
report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee
for Practice Guidelines (Writing Committee to Develop Guidelines for
Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the
European Heart Rhythm Association and the Heart Rhythm Society.
J Am Coll Cardiol 2006;48:e247–e346.
7. Berul CI, Seslar SP, Zimetbaum PJ, et al. Acquired QT syndrome.
In: Triedman J, Levy S, eds. UpToDate, Waltham, MA. Available at:
http://www.uptodateonline.com. Accessed May 4, 2013.