Ibutilide antiarrhythmics

Ibutilide (Corvert) is a structural analog of sotalol and produces cardiac electrophysiological effects similar to those of the antiarrhythmic agents in class III. 

There are no changes in the PR or QRS intervals, which reflects a lack of effect on the conduction velocity. Although there is no relationship between the plasma concentration of ibutilide and its antiarrhythmic effect, there is a dose-related prolongation of the QT interval. The maximum effect on the QT interval is a function of both the dose of ibutilide and the rate of infusion. 

Class III antiarrhythmic drug, which prolongs repolarization by inhibition of the delayed rectifier potassium current (lkr) and by selective enhancement of the slow inward sodium current, Ibutilide has no known negative inotropic effects (53),... 

Stambler BS, Wood MA, Ellenbogen KA. Antiarrhythmic actions of intravenous ibutilide compared with procainamide during human atrial flutter and fibrillation electrophysiological determinants of enhanced conversion efficacy. Circulation 1997 96( 12) 4298-4306. 

Conversion of AF to NSR can also be accomplished with a subset of antiarrhythmic drugs (including 2-7) that act directly on cardiac muscle cells (myocytes) and antagonize either the sodium channel-mediated propagation currents (procainamide 2, flecainide 3, propafenone 4), or the inwardly rectifying (7 ) potassium channel currents (ibutilide 5, dofetilide 6). Some of the antiarrhythmics have actions at both potassium and sodium channels (i.e., dronedarone 7 and its close structural progenitor... 

Other class III antiarrhythmics include sotalol, ibutilide, and dofetilide. These agents do not have a role in the acute treatment of ventricular fibrillation. 

Ibutilide. Ibutilidc, A - 4- 4-(cthylheptylaminoH-hy-droxybutyllphenyllmethanesulfonamidc (Corvert), a class III antiarrhythmic belonging to the mcthancsulfonanilidc class of agents, is indicated for rapid conversion of atrial Hbrillation or atrial flutter to normal sinus rhythm. Unlike dofetilide, it is not highly. specific for the delayed a clificr potassium currents (Ikr) and does have some affinity for. sodium channels. 

Type III antiarrhythmics include agents that specifically prolong refractoriness in atrial and ventricular tissue. This class includes very different drugs bretylium, amiodarone, sotalol, ibutilide, and recently, dofetilide they share the common effect of delaying repolarization by blocking potassium channels. The electrophysiologic actions of bretylium are related to its multifaceted pharmacology. 

Antiarrhythmic/vasodilating drugs Quinidine Procainamide N-Acety I p roca i na m ide Disopyramide Amiodarone Dofetilide Sotalol Ibutilide BepridiH Psychotropics Phenothiazines... 

Ibutilide is an antiarrhythmic agent that prolongs atrial and ventricular action potential duration and refractoriness by activation of a slow inward current (predominantly sodium). It is indicated for rapid conversion of recent onset atrial fibrillation or atrial flutter to sinus rhythm. 

Ibutilide is a classified as a pure class III antiarrhythmic, with novel mechanism of action. 

Antiarrhythmic drugs in Phase III clinical trials are shown in Figure 26.16. Nifekalant is a pyrimidinone Class III agent. Sematilide is a Class III agent that is a benzamide derivative of ibutilide, and SSR-149744c and dronedarone are noniodinated analogues of amiodarone, reportedly with fewer adverse effects than amiodarone. 

Lee KS (1992) Ibutilide, a new compound with potent class III antiarrhythmic activity, activates a slow mward Na current in guinea pig ventricular cells. J Pharmacol Exp Ther 262 99-108 Lee KS, Hume JR, Giles W, Brown AM (1981) Sodium current depression by lidocaine and quinidine in isolated ventricular cells. Nature 291 325-327 Lees-Miller JP, Duan Y, Teng GO, Duff HJ (2000) Molecular determinant of high-affinity dofetilide to HERGl expressed in Xenopus oocytes involvement of S6 sites. Mol Pharmacol 57 367-374... 

When intravenous ibutilide 2 mg was used for cardioversion of atrial fibrillation or flutter in 70 patients taking long-term amiodarone the QT interval was further prolonged (iiom 371 to 479 milliseconds). However, only one patient had an episode of non-sustained torsade de pointes. Ibutilide was effective within 30 minutes of infusion in 39% of patients with atrial flutter, and 54% of patients with fibrillation. Both amiodarone and ibutilide are class III antiarrhythmics and prolong the QT interval, with the consequent risk of torsade de pointes. The manufacturer recommends that they should not be used concurrently. However, the authors of the above report suggest that ibutilide may be useful for cardioversion in those already taking amiodarone. Combined use should be very well monitored. 

Ibutilide, a class in antiarrhythmic, is known to increase the QT interval, so increasing the risk of torsade de pointes arrhythmia. Class Ic antiarrhythmics such as propafenone and flecainide generally shorten the QT interval. It is possible that class Ic antiarrhythmics may usefully attenuate the risk of torsade de pointes with ibutilide, and ibutilide may be... 

The utility and equivalence of the alternative stoichiometric approach have been demonstrated with the enantioselective reduction of 41, a 4-aryl-4-oxo[l,4- " C2]butanoic acid derivative, with (+)-Ipc2BCl to give (4/ )-hydroxyamide 42 in 80% radiochemical yield and >96% e.e. Further reduction with LiAlEL) converted 42 into (4/ )-[l,4- " C2]ibutilide 1431. an antiarrhythmic agenf. ... 

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