A Classification of Antiarrhythmic Actions Reassessed After a Decade of New Drugs

Williams, E. M. Vaughan

doi:10.1002/j.1552-4604.1984.tb01822.x

Cited by 760 publications

(157 citation statements)

References 64 publications

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“…In Figure 3C, the rabbit from Figure 3B has been given 100% oxygen and 1 mEq kg -1 of hypertonic sodium bicarbonate. A regular rhythm returns at a rate of nearly 300 beats min -1 (note the speed of the chart recorder was changed to capture more information) with a narrow QRS complex and restoration of blood pressure Treatment of cocaine arrhythmias overdose situations [9]. In fact, lidocaine has been used successfully to treat wide complex dysrhythmias in patients with toxicity from other sodium channel blockers such as propoxyphene [21] and tricyclic antidepressants [22,23].…”

Section: Treatment Of Arrhythmias Resulting From Cocaine-associated Smentioning

confidence: 99%

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Treatment of patients with cocaine‐induced arrhythmias: bringing the bench to the bedside

Hoffman

2010

Brit J Clinical Pharma

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Widespread use of cocaine and its attendant toxicity has produced a wealth of benchwork studies and small animal investigations that evaluated the effects of cocaine on the cardiovascular system. Despite this wealth of knowledge, very little is known about the frequency or types of arrhythmias in patients with significant cocaine toxicity. The likely aetiologies; catecholamine excess, sodium channel blockade, potassium channel blockade, calcium channel effects, or ischaemia may act alone or in concert to produce a vast array of clinical findings that are modulated by hyperthermia, acidosis, hypoxia and electrolyte abnormalities. The initial paper in the series by Wood & Dargan providing the epidemiological framework of cocaine use and abuse is followed by a detailed review of the electrophysiological effects of cocaine by O'Leary & Hancox. This review is designed to complement the previous papers and focuses on the diagnosis and treatment of patients with cocaine‐associated arrhythmias.

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Section: Treatment Of Arrhythmias Resulting From Cocaine-associated Smentioning

confidence: 99%

“…Stated another way, binding is relatively slow both in onset and offset [9]. The upstroke of the action potential is delayed with resultant prolongation of conduction and impaired myocardial contractility.…”

Section: Sodium Channel Blockadementioning

confidence: 99%

Treatment of patients with cocaine‐induced arrhythmias: bringing the bench to the bedside

Hoffman

2010

Brit J Clinical Pharma

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“…Prolongation of the ECG QRS is the generally accepted measure of sodium channel blocker toxicity following blockade of fast-acting sodium channels at the membrane level [24,25]. In myocytes of the cardiac conduction system this results in a less pronounced up-slope of phase 0 of the action potential, and subsequent reduction in conduction velocity [26].…”

Section: Discussionmentioning

confidence: 99%

Effect of hypertonic saline on electrocardiography QRS duration in rabbit model of bupivacaine toxicity resuscitated by intravenous lipid

Cave

Harvey²,

Prince

et al. 2010

Anaesthesia

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SummaryIntravenous lipid emulsion is established therapy for bupivacaine induced cardiotoxicity. The benefit of combined hypertonic saline and lipid treatment is unexplored. In this experiment, sedated rabbits were resuscitated from bupivacaine‐induced asystole with intravenous lipid according to the Association of Anaesthetists of Great Britain and Ireland’s guideline, or by identical lipid dosing with hypertonic saline: 6 mEq.kg−1 21% sodium chloride. Early electrocardiography QRS prolongation was less with lipid plus hypertonic saline (mean (SD) QRS 0.19 (0.07) s lipid only vs 0.09 (0.01) s lipid plus hypertonic saline; p = 0.003) at 9 min though not different from the lipid only group at 20 min. No difference was observed in rates of circulatory return (7/10 lipid only and 9/10 lipid plus hypertonic saline; p = 0.58) or survival (5/10 lipid only and 6/10 lipid plus hypertonic saline; p = 1.00). Some benefit to cardiac conduction may be afforded by hypertonic saline co‐administered with lipid emulsion in bupivacaine‐induced cardiotoxicity.

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“…These drugs include ibutilide, somatilide, sotalol, azimilide, droneradone and amiodarone, which elicit their actions by blocking one or more cardiac potassium channels, such as I Kr , I Ks and I Kur , among others. The class III antiarrhythmic drugs have been subject to extensive clinical investigation as safer and more effective alternatives to class I drugs, which exhibit recognised risks in selected populations [5][6][7] . However, numerous noncardiac side effects, such as nausea, drizzles and headaches, also frequently occur with the use of class III antiarrhythmic drugs.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG channel and three neuronal potassium channels

Sun

Zhou

et al. 2012

Acta Pharmacol Sin

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Aim: This study was conducted to test the selectivity of DC031050 on cardiac and neuronal potassium channels. Methods: Human ether-à-go-go related gene (hERG), KCNQ and Kv1.2 channels were expressed in CHO cells. The delayed rectifier potassium current (I K ) was recorded from dissociated hippocampal pyramidal neurons of neonatal rats. Whole-cell voltage patch clamp was used to record the voltage-activated potassium currents. Drug-containing solution was delivered using a RSC-100 Rapid Solution Changer. Results: Both DC031050 and dofetilide potently inhibited hERG currents with IC 50 values of 2.3±1.0 and 17.9±1.2 nmol/L, respectively. DC031050 inhibited the I K current with an IC 50 value of 2.7±1.5 μmol/L, which was >1000 times the concentration required to inhibit hERG current. DC031050 at 3 μmol/L did not significantly affect the voltage-dependence of the steady activation, steady inactivation of I K , or the rate of I K from inactivation. Intracellular application of DC031050 (5 μmol/L) was insufficient to inhibit I K . DC031050 up to 10 μmol/L had no effects on KCNQ2 and Kv1.2 channel currents. Conclusion: DC031050 is a highly selective hERG potassium channel blocker with a substantial safety margin of activity over neuronal potassium channels, thus holds significant potential for therapeutic application as a class III antiarrhythmic agent.

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A Classification of Antiarrhythmic Actions Reassessed After a Decade of New Drugs

Cited by 760 publications

References 64 publications

Treatment of patients with cocaine‐induced arrhythmias: bringing the bench to the bedside

Treatment of patients with cocaine‐induced arrhythmias: bringing the bench to the bedside

Effect of hypertonic saline on electrocardiography QRS duration in rabbit model of bupivacaine toxicity resuscitated by intravenous lipid

Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG channel and three neuronal potassium channels

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