Therapeutic use of ibutilide
- Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA
Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA
- Professor of Medicine
- Director, Center for Women’s Health
- Columbia University Medical Center
Ibutilide is a class III antiarrhythmic drug available only for intravenous use for the termination of atrial arrhythmias. An oral form is not available because of extensive first-pass metabolism .
The physiology and pharmacology of ibutilide use and the side effects that can occur will be reviewed here. The pharmacokinetics of ibutilide, drug interactions, and the various clinical settings in which ibutilide might be used are discussed in detail separately.
MECHANISMS OF ACTION
Cellular mechanisms — Like other class III antiarrhythmic agents (table 1), ibutilide prolongs repolarization in atrial and ventricular myocardium [1,2]. The class III drugs block IKr, the rapid component of the cardiac delayed rectifier potassium current. This results in prolonged repolarization, increased action potential duration, and lengthening of the refractory period . Ibutilide increases the refractoriness of atrial and ventricular myocardium, the atrioventricular node, His-Purkinje system, and accessory pathway . In addition, ibutilide activates a slow, delayed inward sodium current that occurs early during repolarization [1,4]. (See "Myocardial action potential and action of antiarrhythmic drugs" and 'Major side effects' below.)
Effects on the ECG — Ibutilide has two major effects on the electrocardiogram (ECG): it produces mild slowing of the sinus rate and, as with other class III antiarrhythmic drugs, prolongation of the QT interval. There is no effect on the PR interval or QRS duration.
The degree of QT prolongation associated with ibutilide is related to the dose, the rate of infusion, and the serum concentration . Prolongation of the QT interval provides the substrate for torsades de pointes (TdP), a polymorphic ventricular tachycardia. The QT interval returns to baseline within two to four hours after stopping the infusion. (See 'Proarrhythmia' below and 'Discontinuing ibutilide infusion' below.)
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- MECHANISMS OF ACTION
- Cellular mechanisms
- Effects on the ECG
- Mechanism of proarrhythmic effect
- CLINICAL USES
- Atrial fibrillation
- Atrial flutter
- Combination ibutilide plus esmolol for recent onset atrial fibrillation
- Ibutilide in children and in patients with congenital heart disease
- Role of magnesium
- MAJOR SIDE EFFECTS
- Other cardiac toxicities
- Hemodynamic effects
- Discontinuing ibutilide infusion
- SUMMARY AND RECOMMENDATIONS