Sotalol intoxication with prolonged Q-T interval and severe tachyarrhythmias.

Elonen, Erkki; Neuvonen, P J; Tarssanen, Leo; Kala, R

doi:10.1136/bmj.1.6172.1184

Cited by 59 publications

(18 citation statements)

References 2 publications

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“…There can be no doubt, however, that both compounds exhibit considerably greater potency on guinea-pig ventricular fibres than on atrial fibres. Similar differences (for DL-sotalol) were noted in early studies (Singh & Vaughan Williams, 1970;Strauss et al, 1970), and more recently, Kato et al, (1986) Plasma concentrations of DL-sotalol in patients on long-term oral therapy with this agent are usually less than 10 JAM and certainly below 20 gAM (Elonen et al, 1979;Neuvonen et al, 1981). Levels up to approximately 40 JAM have been found in patients immediately following acute intravenous injection of DL-sotalol (Nademanee et al, 1985) but it is unlikely that the concentrations would remain so high for long (Campbell et al, 1985).…”

Section: Discussionmentioning

confidence: 49%

“…Levels up to approximately 40 JAM have been found in patients immediately following acute intravenous injection of DL-sotalol (Nademanee et al, 1985) but it is unlikely that the concentrations would remain so high for long (Campbell et al, 1985). Indeed, severe toxicity has been described at blood levels of 25 gM and 53 JM following deliberate overdosage (Elonen et al, 1979 Effects on human atrial cells DL-Sotalol has been shown to be beneficial in the treatment of atrial tachyarrhythmias in man at concentrations below 10 JAM (Campbell et al, 1985) and to prolong human atrial repolarization in similar concentrations (measured as monophasic action potential duration; Echt et al, 1982;Hayward & Taggart, 1986). These facts strongly suggest the possibility that human atrial cells may be more sensitive than those of rabbits or guinea-pigs to the class III actions of solatol.…”

Section: Discussionmentioning

confidence: 99%

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Cellular electrophysiological effects of d‐and dl‐sotalol in guinea‐pig sinoatrial node, atrium and ventricle and human atrium: differential tissue sensitivity

Campbell¹

1987

British J Pharmacology

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1 The effects of racemic DL-sotalol and D-sotalol on guinea-pig sino-atrial node, atrium and ventricle and on human atrium were studied using standard microelectrode techniques. Both compounds increased spontaneous sinus node cycle length largely by prolonging the repolarization phase of the action potentials. This effect was attributed to blockade of outward potassium current. 2 Ventricular action potential duration was similarly prolonged by DL-sotalol at concentrations of 5 -50 JLM.3 DL-Sotalol 1-5011M had no effect on guinea-pig atrial action potential duration and D-sotalol produced minor prolongation only at the highest concentration (50 pM).4 Human atrial action potentials were, however, significantly prolonged by both DL-and D-sotalol 10 JM. This indicates differential sensitivities to sotalol for human and guinea-pig atrium and explains the ability of sotalol to prolong atrial monophasic action potential duration in clinical studies.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Cellular electrophysiological effects of d‐and dl‐sotalol in guinea‐pig sinoatrial node, atrium and ventricle and human atrium: differential tissue sensitivity

Campbell¹

1987

British J Pharmacology

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“…However, it has been known that lifethreatening arrhythmias such as polymorphic ventricular tachydardia or torsack de pointes could be developed in case of overdosage or intoxication of class I11 antiarrhythmic drugs [Elonen et al, 1979;Herre and Thompson, 1985;Sclarovsky et al, 19831. To examine whether such arrhythmias are inducible at the toxic doses, MS-551(2 mg/kg/min i.v.) was administered by continuous infusion for 50 min in anesthetized dogs.…”

Section: Discussionmentioning

confidence: 99%

MS‐551: Pharmacological profile of a novel class III antiarrhythmic agent

Kamiya

Ishii

Yoshihara

et al. 1993

Drug Development Research

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The class Ill antiarrhythmic agent properties of the novel compound MS-551 (1,3- dimethyl-6-{(2-[N-(2-hydroxyethyl)-3-(4-nitrophenyl)propylaminolethylamino} 2,4 (IH,3H)-pyrimidinedione hydrochloride) have been characterized in vitro and in vivo. Using isolated canine Purkinje fibers, the effect of MS-551 on the action potentials was studied. MS-551 (0.1-10 p,g/ml) caused a uniform and concentration-dependent increase in action potential duration without changing parameters of action potential depolarization. In anesthetized open-chested dogs, MS-551 (0.1-10 mg/kg i,v.) produced a dose-dependent increase in both atrial and ventricular effective refractory periods (ERP) with QT, prolongation. At 0.3 mg/kg i.v., atrial and ventricular ERP were significantly increased 28 2 4 msec and 12 2 2 msec, respectively, and the minimum effective plasma concentration of MS-551 for atrial ERP prolongation was approximately 0.1 p,g/mI. However, MS-551 did not slow intracardiac conduction time (A-HI H-V) even at the highest dose studied (30 mg/kg i.v.). These data suggest that MS-551 has a "pure" class Ill electrophysiological property in dogs. Furthermore, we compared the effects of MS-551 on the hemodynamics in anesthetized dogs with those of d-sotalol. MS-551 (0.1-3 mg/kg) produced dose-dependent decrease in heart rate with QT, prolongation and slight increase in LVdP/dtmax. In contrast, d-sotalol (0.1-10 mg/kg i.v.) decreased heart rate, mean arterial pressure, LVdP/dtmax and aortic flow in a dose-dependent manner. Moreover, we reassessed in anesthetized dogs the cardiovascular toxicity of continuously infused MS-551 (2 mg/kg/min for 50 min). At the end of the infusion (total dose: MS-551 100 mg/kg), LVdP/dtmax was decreased 23%, but QT, prolongation never exceeded 30%. Thus, arrhythmias, such as torsade depointes, were not seen. In conclusion, MS-551 appears to be a pure and potent class Ill antiarrhythmic agent with a favourable hemodynamic profile. o 1993 WiIey-Liss, Inc.

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“…The occurrence of TdP is especially likely in the setting of renal failure, hypokalemia, and bradycardia at high drug concentrations. The proarrhythmia is also likely in situations in which there is preexisting lengthening of the QT interval (100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110). Neuvonen et al (106,107) reported a correlation between the serum sotalol concentration and prolongation of the QTc interval.…”

Section: Proarrhythmic and Other Adverse Electrophysiologicmentioning

confidence: 96%

Review : Sotalol: Current Status and Expanding Indications

Singh

1999

J Cardiovasc Pharmacol Ther

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BACKGROUND: The role of antiarrhythmic drug therapy continues to undergo major changes. The change is necessitated by the advent of invasive interventional procedures, such as catheter ablation of arrhythmias and the use of implantable devices for sensing and terminating life-threatening ventricular arrhythmias and symptomatically traublesome supraventricular arrhythmias. Many conventional and time-honored drugs, such as sodium channel blockers, have been found either to be ineffective or to have the potential to produce serious proarrhythmic reactions. Attention is therefore focused on compounds that prolong repolarization and reduce sympathetic stimulation. Two compounds, amiodarone and sotalol, have emerged as prototypes of drugs of the future. METHODS AND RESULTS: This review focuses on sotalol for controlling supraventricular and ventricular tachyarrhythmias. Sotalol is a major antiarrhythmic agent that combines potent class III action with nonselective beta-blocking properties. The drug's pharmacokinetics is simple. Its elimination half-life is 10-15 hours, the drug being excreted almost exclusively by the kidneys. Sotalol's pharmacokinetics allows development of optimal dosing for initiation of therapy relative to changes in creatinine clearance with further dose adjustment by monitoring the QT interval on the surface electrocardiogram. The compound exerts broad-spectrum antiarrhythmic actions in supraventricular and ventricular arrhythmias. It prevents inducible ventricular tachycardia (VT) and ventricular fibrillation (VF) in approximately 30% of patients with a higher figure for the suppression of spontaneously occurring arrhythmias documented on Holter recordings. CONCLUSIONS: The major role of sotalol is in the management of VT/VF often in conjunction with an implantable cardioverter/defibrillator, in which context it lowere the defibrillation threshold. Sotalol is superior to class I agents, especially in VT/VF and in survivors of cardiac arrest. Sotalol has emerged as a major antifibrillatory compound for the control of life-threatening ventricular arrhythmias as the main indication. Data have indicated its potential for the maintenance of stability of sinus rhythm in patients with atrial fibrillation and flutter after electrical conversion and in preventing their occurrence in a variety of clinical settings.

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Sotalol intoxication with prolonged Q-T interval and severe tachyarrhythmias.

Cited by 59 publications

References 2 publications

Cellular electrophysiological effects of d‐and dl‐sotalol in guinea‐pig sinoatrial node, atrium and ventricle and human atrium: differential tissue sensitivity

Cellular electrophysiological effects of d‐and dl‐sotalol in guinea‐pig sinoatrial node, atrium and ventricle and human atrium: differential tissue sensitivity

MS‐551: Pharmacological profile of a novel class III antiarrhythmic agent

Review : Sotalol: Current Status and Expanding Indications

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