Comparison of intravenous mexiletine and lidocaine for the treatment of ventricular arrhythmias

Lui, Henry; Harris, Fred J.; Chan, Ming C.; Lee, Garrett; Mason, Dean T.

doi:10.1016/0002-8703(86)90343-1

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…The fold changes induced by mexiletine in both Na v 1.5 and Na v 1.7 were also more prominent compared to the same concentration of lidocaine. Clinical studies reveal a comparison between intravenous mexiletine and lidocaine for the treatment of ventricular arrhythmias by showing that mexiletine results in greater suppression of ventricular premature depolarization [33]. This is consistent with our finding that mexiletine had a strong impact on recovery from inactivation of Na v 1.5 channel than lidocaine.…”

Section: Discussionsupporting

confidence: 90%

Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine

Wang

et al. 2015

PLoS ONE

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Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that are considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias and relief of pain. To gain mechanistic insights into action of anti-arrhythmics, we characterized biophysical properties of Nav1.5 and Nav1.7 channels stably expressed in HEK293 cells and compared their use-dependent block in response to mexiletine and lidocaine using whole-cell patch clamp recordings. While the voltage-dependent activation of Nav1.5 or Nav1.7 was not affected by mexiletine and lidocaine, the steady-state fast and slow inactivation of Nav1.5 and Nav1.7 were significantly shifted to hyperpolarized direction by either mexiletine or lidocaine in dose-dependent manner. Both mexiletine and lidocaine enhanced the slow component of closed-state inactivation, with mexiletine exerting stronger inhibition on either Nav1.5 or Nav1.7. The recovery from inactivation of Nav1.5 or Nav1.7 was significantly prolonged by mexiletine compared to lidocaine. Furthermore, mexiletine displayed a pronounced and prominent use-dependent inhibition of Nav1.5 than lidocaine, but not Nav1.7 channels. Taken together, our findings demonstrate differential responses to blockade by mexiletine and lidocaine that preferentially affect the gating of Nav1.5, as compared to Nav1.7; and mexiletine exhibits stronger use-dependent block of Nav1.5. The differential gating properties of Nav1.5 and Nav1.7 in response to mexiletine and lidocaine may help explain the drug effectiveness and advance in new designs of safe and specific sodium channel blockers for treatment of cardiac arrhythmia or pain.

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Section: Discussionsupporting

confidence: 90%

Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine

Wang

et al. 2015

PLoS ONE

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“…Similar to analgesia studies, several have concluded AEs were either comparable to placebo or negligible. [22][23][24] Morganroth et al, 25 however, found AEs in 18% of patients with an 8% discontinuation rate, closer to the findings of our study. Rademaker et al 26 evaluated the use of intravenous lidocaine for prophylaxis following proven or suspected myocardial infarction.…”

Section: Discussionsupporting

confidence: 91%

“…As the quality of safety data for lidocaine for postoperative pain is quite low, analyses of lidocaine for ventricular arrythmias may be useful. Similar to analgesia studies, several have concluded AEs were either comparable to placebo or negligible 22–24. Morganroth et al,25 however, found AEs in 18% of patients with an 8% discontinuation rate, closer to the findings of our study.…”

Section: Discussionsupporting

confidence: 90%

Evaluating the Safety of Continuous Infusion Lidocaine for Postoperative Pain

Schuler

Lupi

Szumita

et al. 2021

The Clinical Journal of Pain

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Objectives: The aim was to evaluate the safety of intravenous lidocaine for postoperative pain and the impact on opioid requirements and pain scores Materials and Methods: This was a single-center, retrospective, single-arm analysis of adult patients who received intravenous lidocaine for postoperative pain from January 2016 to December 2019. Patients were excluded if they received lidocaine for any indication other than pain or if lidocaine was only given intraoperatively. The primary outcome of this analysis was to determine the incidence of adverse effects (AEs) and the reason for discontinuation of lidocaine. Secondary outcomes included median daily pain scores (visual analog scale and Critical-Care Pain Observation Tool) and opioid consumption (daily morphine milligram equivalents) 24 hours before infusion and during day 1.Results: A total of 452 patients were evaluated of which 298 (65.9%) patients met inclusion criteria. Of the 154 patients excluded, 153 did not receive lidocaine postoperatively. The median duration of infusion was 34 [20:48] hours with a median initial and maintenance rate of 1 mg/kg/h dosed on ideal body weight. In our analysis, 174 (58.4%) patients had a documented AE during infusion and 38 (12.8%) had lidocaine discontinued because of an AE. The most common AE was nausea in 62 (20.8%) patients and the most common reason for discontinuation was confusion in 8 (2.7%) patients. Daily morphine milligram equivalents (P < 0.001) and visual analog scale (P < 0.001) significantly decreased when comparing 24 hours before infusion and day 1. Conclusion:Although a majority of patients receiving lidocaine for postoperative pain experienced an AE, this did not result in discontinuation in most patients.

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“…These experiments demonstrated that I HERG is not entirely resistant to blockade by LIG, but that this drug is a blocker of rather low potency. Our data suggest that little I HERG blockade would be anticipated to occur at therapeutic lignocaine concentrations (*7 ± 15 mM; Lui et al, 1986). For this reason, the e ects of LIG on I HERG were not investigated in further detail.…”

Section: Comparison With Ligmentioning

confidence: 87%

Inhibition of the current of heterologously expressed HERG potassium channels by flecainide and comparison with quinidine, propafenone and lignocaine

Paul¹,

Witchel²,

Hancox³

2002

British J Pharmacology

150

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1 The inhibition of the cardiac`rapid' delayed recti®er current (I Kr ) and its cloned equivalent HERG mediate QT interval prolonging e ects of a wide range of clinically used drugs. In this study, we investigated the e ects of the Class Ic antiarrhythmic agent¯ecainide (FLEC) on ionic current (I HERG ) mediated by cloned HERG channels at 378C . We also compared the inhibitory potency of FLEC with other Class I agents: quinidine (QUIN, Class Ia); lignocaine (LIG, Class Ib) and propafenone (PROPAF, Class Ic). 2 Whole cell voltage clamp recordings of I HERG were made from an HEK293 cell line stably expressing HERG. FLEC inhibited I HERG`t ails' following test pulses to +30 mV with an IC 50 of 3.91+0.68 mM (mean+s.e.mean) and a Hill co-e cient close to 1 (0.76+0.09).3 In experiments in which I HERG tails were monitored following voltage commands to a range of test potentials, I HERG inhibition by FLEC was observed to be voltage-dependent and to be associated with a *75 mV shift of the activation curve for the current. Voltage-dependence of inhibition was greatest over the range of potentials corresponding to the steep portion of the I HERG activation curve. The time-course of I HERG tail deactivation was not signi®cantly altered by FLEC. 4 In experiments in which 10 s depolarizing pulses were applied from 780 to 0 mV, the level of current inhibition by FLEC did not increase between 1 and 10 s. Some time-dependence of inhibition was observed during the ®rst 200 ± 300 ms of depolarization. This observation and the voltage-dependence of inhibition are collectively consistent with FLEC exerting a rapid open channel state inhibition of I HERG . 5 Under similar recording conditions QUIN inhibited I HERG with an IC 50 of 0.41+0.04 mM and PROPAF inhibited I HERG with an IC 50 of 0.44+0.07 mM. Similar to FLEC, both QUIN and PROPAF showed voltage-dependence of inhibition and blockade developed rapidly during a sustained depolarization. 6 LIG showed little e ect on I HERG at low micromolar concentrations, but could inhibit the current at higher concentrations; the observed IC 50 was 262.90+22.40 mM. 7 Our data are consistent with FLEC, PROPAF and QUIN exerting I HERG blockade at clinically relevant concentrations. The rank potency as HERG blockers of the Class I drugs tested in this study was QUIN=PROPAF4FLEC44LIG. British Journal of Pharmacology (2002) 136, 717 ± 729 Keywords: Antiarrhythmic; Class Ia; Class Ib; Class Ic;¯ecainide; HERG; I Kr ; QT interval; QT prolongation; quinidine Abbreviations: ANOVA, analysis of variance; d, fractional distance in the transmembrane ®eld sensed at drug receptor site; DISO, disopyramide; FLEC,¯ecainide; HERG, Human ether-a-go-go related gene; IC 50 , half maximal inhibitory drug concentration; I Ca,L , L-type calcium current; I HERG , current mediated by the HERG channel; I K , delayed recti®er potassium current; I Kr`r apid' delayed recti®er potassium current; I Ks`s low' delayed recti®er potassium current; I to , transient outward potassium current; k, slope factor describing voltage de...

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Comparison of intravenous mexiletine and lidocaine for the treatment of ventricular arrhythmias

Cited by 7 publications

References 12 publications

Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine

Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine

Evaluating the Safety of Continuous Infusion Lidocaine for Postoperative Pain

Inhibition of the current of heterologously expressed HERG potassium channels by flecainide and comparison with quinidine, propafenone and lignocaine

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