• The Korean Journal of Physiology and Pharmacology
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• 제17권6호
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• pp.485-491
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• 2013

The present study was designed to investigate the putative effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion followed by reperfusion, produced a significant rise in cerebral infarct size along with impairment of grip strength and motor coordination in Swiss albino mice. Administration of carbamazepine (16 mg/kg, i.p.) before global cerebral ischaemia significantly attenuated cerebral infarct size and improved the motor performance. However, administration of indomethacin (100 mg/kg, i.p.) attenuated the neuroprotective effect of carbamazepine. Mexiletine (50 mg/kg, i.p.) did not produce significant neuroprotective effect. It may be concluded that the neuroprotective effect of carbamazepine may be due to increase in synthesis of neurosteroids perhaps by activating enzyme ($3{\alpha}$ HSD) as indomethacin attenuated the neuroprotective effect of carbamazepine. The sodium channel blocking effect of carbamazepine may not be involved in neuroprotection as mexiletine, a sodium channel blocker, did not produce significant neuroprotective effect.

• Neonatal Medicine
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• 제28권1호
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• pp.59-63
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• 2021

An important, albeit rare, cause of fetal bradycardia is long QT syndrome (LQTS). Congenital LQTS is an ion channelopathy caused by mutations in genes encoding cardiac ion channel proteins. Fetal onset of LQTS imposes high risk of life-threatening tachyarrhythmias and sudden cardiac death. Here, we report the case of a female newborn with fetal onset of bradycardia and a 2:1 atrioventricular (AV) block. After birth, a 12-lead electrocardiogram (ECG) revealed bradycardia with QT prolongation of a corrected QT (QTc) interval of 680 ms and pseudo 2:1 AV block. Genetic testing identified a heterozygous Gly402Ser (c.1204G>A) mutation in CACNA1C, confirming the diagnosis of LQTS type 8 (LQT8). The patient received propranolol at a daily dose of 2 mg/kg. Mexiletine was subsequently administered owing to the sustained prolongation of the QT interval and pseudo 2:1 AV block. One week after mexiletine inception, the ECG still showed QT interval prolongation (QTc, 632 ms), but no AV block was observed. There were no life-threatening tachyarrhythmias in a follow-up period of 13 months.

• 한국임상수의학회지
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• 제27권4호
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• pp.440-444
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• 2010

5.2 kg의 7살령 중성화 된 수컷 시추가 심각한 신경증상(paddling, 무의식, 실명, 발작)으로 내원하였다. 내원 당시 ECG 상에 심실 유래의 심박동 약 140회의 가속성 심실 고유박동(AVIR)이 지속적으로 나타났다. 이 환축은 자기공명영상법(MRI)과 뇌척수액검사(CSF)를 통해 파종성 육아종성 뇌수막염(GME)로 잠정 진단 내려졌다. 신경증상은 스테로이드제와 항경련제, 이뇨제, 항생제, 20% 만니톨 정맥 주사 등으로 호전 되었으며 부정맥은(AIVR) mexiletin으로 통제되었다. 신경학적인 문제에 대한 응급 처치 후 증상의 호전에도 불구하고 항부정맥제 처치 없이는 심장의 리듬이 불안정 했기 때문에 항부정맥 처치는 신경증상이 완전히 소실 될 때까지 유지되었다.

• Journal of Chest Surgery
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• 제25권6호
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• pp.672-677
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• 1992

This is a clinical review of the results from electric cardioversion and pharmacological therapy used in our hospital for reverting cardiac arrythmia in patients with mitral valve surgery between Jan. 1990 and Jun. 1991. Of 62 evaluated patients, 16 patients had regular sinus rhythm and the other 46 had arrhythmias [42; atrial fibrillation 1; atrial flutter 1; premature ventricular contraction] preoperatively. In 2 of patients with sinus rhythm, atrial fibrillation newly developed after surgery and was converted into sinus rhythm soon by intravenous administration of digoxin. Remaining 14 patient resumed sinus rhythm spontaneously. In patients with preoperative arrythmia, 3 patients reverted into sinus rhythm from atrial fibrillation by electric cardioversion at operative field, 1 patient by lidocain and mexiletine, 4 patients by combined use of digoxin and verapamil, 4 patients by 2 times of oral quinidine and 9 patient by long term use of oral amiodarone. Throughout this consecutive trials of anti-arrhythmic drugs and electric cardioversion, Conversion into normal sinus rhythm occurred in 48% of patients with arrhythmia developed after mitral valve surgery.

• 대한치과의사협회지
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• 제49권6호
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• pp.327-333
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• 2011

Clinically, treatment goal of neuropathic pain focused on not elimination of etiology but management and control of symptoms because we don't know certain about clear etiology of neuropathic pain yet. The drugs used for the management of neuropathic pain were classified as drugs with strong evidence for benefit(antidepressants, anticonvulsants, opioid analgesics etc.), modest evidence for benefit(mexiletine, carbamazepine, clonidine etc.), preliminary evidence for benefit(NSAIDs, dextromethorphan, topiramate etc.). Finally, the treatment for trigeminal neuralgia was outlined separately since this disorder responds to a different group of drugs than other neuropathic pain conditions.

• The Korean Journal of Physiology and Pharmacology
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• 제27권3호
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• pp.267-275
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• 2023

Cardiotoxicity, particularly drug-induced Torsades de Pointes (TdP), is a concern in drug safety assessment. The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (human iPSC-CMs) has become an attractive human-based platform for predicting cardiotoxicity. Moreover, electrophysiological assessment of multiple cardiac ion channel blocks is emerging as an important parameter to recapitulate proarrhythmic cardiotoxicity. Therefore, we aimed to establish a novel in vitro multiple cardiac ion channel screening-based method using human iPSC-CMs to predict the drug-induced arrhythmogenic risk. To explain the cellular mechanisms underlying the cardiotoxicity of three representative TdP high- (sotalol), intermediate- (chlorpromazine), and low-risk (mexiletine) drugs, and their effects on the cardiac action potential (AP) waveform and voltage-gated ion channels were explored using human iPSC-CMs. In a proof-of-principle experiment, we investigated the effects of cardioactive channel inhibitors on the electrophysiological profile of human iPSC-CMs before evaluating the cardiotoxicity of these drugs. In human iPSC-CMs, sotalol prolonged the AP duration and reduced the total amplitude (TA) via selective inhibition of I_Kr and I_Na currents, which are associated with an increased risk of ventricular tachycardia TdP. In contrast, chlorpromazine did not affect the TA; however, it slightly increased AP duration via balanced inhibition of I_Kr and I_Ca currents. Moreover, mexiletine did not affect the TA, yet slightly reduced the AP duration via dominant inhibition of I_Ca currents, which are associated with a decreased risk of ventricular tachycardia TdP. Based on these results, we suggest that human iPSC-CMs can be extended to other preclinical protocols and can supplement drug safety assessments.

• Journal of Yeungnam Medical Science
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• 제16권1호
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• pp.125-130
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• 1999

저자들은 최근 25세 여자 환자로 뚜렷한 가족력이 없으면서 3-4세경부터 발생한 근육의 강직현상과 현저한 근비대소견이 있는 환자를 경험하였다. 임상적으로 타진성 근긴장증을 보이고 전기생리적 검사로 새끼손가락 외향근에서의 운동과 반복신경자극에서 복합근육활동전위의 감소를 보였으며, 이두박근의 근생검 소견상 용적이 증가된 근섬유와 중심핵화현상이 관찰되었다. 환자는 mexiletin 경구 투여후 근육의 강직현상이 다소 호전되었다. 이에 문헌고찰과 함께 Becker형 선천성 근긴장증 1례를 보고하는 바이다.

• The Korean Journal of Pain
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• 제23권2호
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• pp.99-108
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• 2010

Chronic pain is a multifactorial condition with both physical and psychological symptoms, and it affects around 20% of the population in the developed world. In spite of outstanding advances in pain management over the past decades, chronic pain remains a significant problem. This article provides a mechanism- and evidence-based approach to improve the outcome for pharmacologic management of chronic pain. The usual approach to treat mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate, and if there is an element of sleep deprivation, then it is reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial with one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate an earlier trial of a long term opioid. Skeletal muscle relaxants and topicals may also be appropriate as single agents or in combination. Meanwhile, the steps of pharmacologic treatments for neuropathic pain include (1) certain antidepressants (tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors), calcium channel ${\alpha}2-{\delta}$ ligands (gabapentin and pregabalin) and topical lidocaine, (2) opioid analgesics and tramadol (for first-line use in selected clinical circumstances) and (3) certain other antidepressant and antiepileptic medications (topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists). It is essential to have a thorough understanding about the different pain mechanisms of chronic pain and evidence-based multi-mechanistic treatment. It is also essential to increase the individualization of treatment.