Quinidine Research Articles

A Case of Psoriasis Induced After Allergic Drug Eruption due to Quinidine Sulfate

A Case of Psoriasis Induced After Allergic Drug Eruption due to Quinidine Sulfate

Treatment of Atrial Fibrillation with Quinidine Sulfate in the Racehorse

Treatment of Atrial Fibrillation with Quinidine Sulfate in the Racehorse

Pharmacokinetic Studies on Quinidine Sulfate Orally Administered in Horses

Pharmacokinetic Studies on Quinidine Sulfate Orally Administered in Horses

‘Orphan drugs’ in cardiology: nadolol and quinidine

The recent withdrawal from the market of nadolol (Corgard; Bristol-Myers Squibb, Sermoneta, Italy) and quinidine polygalacturonate (Ritmocor; Malesci, Bagno A Ripoli, Italy) has been causing clinical problems to many cardiologists and patients, frequently leading to discontinuance of an effective and well-tolerated pharmacological treatment. Nadolol is useful in the treatment of severe and refractory arrhythmias, particularly in some genetically determined ion-channel diseases, such as long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia.Quinidine is still used in refractory atrial fibrillation recurrences. Recent studies have demonstrated the clinical efficacy of quinidine in the treatment of rare genetically determined ion-channel diseases at high risk of sudden death, such as Brugada syndrome and short-QT syndrome.We hope that scientific societies can influence healthcare and pharmaceutical institutions, in order to restore the availability of two cardiovascular drugs that are extremely important in the care of arrhythmic patients.

Rapid LC-MS Drug Metabolite Profiling Using Microsomal Enzyme Bioreactors in a Parallel Processing Format

Silica nanoparticle bioreactors featuring thin films of enzymes and polyions were utilized in a novel high-throughput 96-well plate format for drug metabolism profiling. The utility of the approach was illustrated by investigating the metabolism of the drugs diclofenac (DCF), troglitazone (TGZ), and raloxifene, for which we observed known metabolic oxidation and bioconjugation pathways and turnover rates. A broad range of enzymes was included by utilizing human liver (HLM), rat liver (RLM) and bicistronic human-cyt P450 3A4 (bicis.-3A4) microsomes as enzyme sources. This parallel approach significantly shortens sample preparation steps compared to an earlier manual processing with nanoparticle bioreactors, allowing a range of significant enzyme reactions to be processed simultaneously. Enzyme turnover rates using the microsomal bioreactors were 2-3 fold larger compared to using conventional microsomal dispersions, most likely because of better accessibility of the enzymes. Ketoconazole (KET) and quinidine (QIN), substrates specific to cyt P450 3A enzymes, were used to demonstrate applicability to establish potentially toxic drug-drug interactions involving enzyme inhibition and acceleration.

An Equine Case of Atrial Fibrillation Treated with Quinidine Sulfate

An Equine Case of Atrial Fibrillation Treated with Quinidine Sulfate

Plasma and Tissue Distribution of Quinidine Sulfate Administered by Various Routes in Cows

Plasma and Tissue Distribution of Quinidine Sulfate Administered by Various Routes in Cows

Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols.

BackgroundThe parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel remains the main drug used for schistosomiasis treatment, and reliance on the single therapy has been prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within the S. mansoni gut is a major heme detoxification route with lipid droplets involved in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of three antimalarial compounds, quinine (QN), quinidine (QND) and quinacrine (QCR) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches.Methodology/Principal FindingsTreatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN, and QND (75 mg/kg/day) from the 11th to 17th day after infection caused significant decreases in worm burden (39%–61%) and egg production (42%–98%). Hz formation was significantly inhibited (40%–65%) in female worms recovered from QN- and QND-treated mice and correlated with reduction in the female worm burden. We also observed that QN treatment promoted remarkable ultrastructural changes in male and female worms, particularly in the gut epithelium and reduced the granulomatous reaction to parasite eggs trapped in the liver. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms.ConclusionsThe overall significant reduction in several disease burden parameters by the antimalarial quinoline methanols indicates that interference with Hz formation in S. mansoni represents an important mechanism of schistosomicidal action of these compounds and points out the heme crystallization process as a valid chemotherapeutic target to treat schistosomiasis.

Resonance light scattering study on the interaction between quinidine sulfate and congo red and its analytical application

The interaction between quinidine sulfate (QDS) and congo red (CR) was studied using resonance light scattering (RLS) technique, ultraviolet-visual spectrophotometry and fluorimetry. In weak acidic medium, QDS reacts with CR to form a supermolecular complex which results in the enhanced RLS intensity. Some important interacting parameters, such as the solution acidity and CR concentration, salt effect and addition order of the reagents, were investigated and optimized. Under the optimum conditions, it was found that the enhanced RLS intensity was in proportion to the concentration of QDS in the range 0.2-8.4 microg mL(-1). The corresponding detection limit was 12.0 ng mL(-1). The results showed that this new method enabled simple, sensitive and rapid determination of QDS and was used for the determination of QDS in urine and simulated huamn serum samples.

Biowaiver monographs for immediate release solid oral dosage forms: Quinidine sulfate

Literature data are reviewed relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing quinidine sulfate. Quinidine sulfate's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. The available data are not fully conclusive, but do suggest that quinidine sulfate is highly soluble and moderately to highly permeable and would likely be assigned to BCS Class I (or at worst BCS III). In view of the inconclusiveness of the data and, more important, quinidine's narrow therapeutic window and critical indication, a biowaiver based approval of quinidine containing dosage forms cannot be recommended for either new multisource drug products or for major postapproval changes (variations) to existing drug products.

Drug-induced esophagitis

Drug-induced esophagitis is being recognized increasingly in the past few years. Since 1970 more than 650 cases have been reported worldwide caused by 30 or more medications. We have reviewed these cases with a view to classifying this disease based on underlying pathological mechanism. Drug-induced esophageal injury tends to occur at the anatomical site of narrowing, with the middle third behind the left atrium predominating (75.6%). The disease is broadly classified into two groups. The first group being transient and self-limiting as exemplified by the tetracycline group induced injury (65.8%). The second is the persistent esophagitis group, often with stricture, with two distinct entities: (i) patients on nonsteroidal anti-inflammatory agents whose injury is aggravated by gastroesophageal reflux (21.8%) (reflux aggravated); and (ii) patients with potasium chloride and quinidine sulphate induced injury (12.4%) (persistent drug injury). Severe esophageal injury has been reported in some women taking biphosphonates as treatment for postmenopausal osteoporosis. Endoscopic findings in such patients with esophageal injury generally suggested a chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Most cases of medication-induced esophageal injury heal without intervention within a few days. Thus, the most important aspect of therapy is to make the correct diagnosis and then to avoid reinjury with the drug. When possible, potentially caustic oral medications should be discontinued.

Use of propafenone for conversion of chronic atrial fibrillation in horses

To investigate effects of IV administration of propafenone for naturally occurring and experimentally induced chronic atrial fibrillation in horses. 2 horses with naturally occurring atrial fibrillation and 4 horses with pacing-induced atrial fibrillation. Horses received a bolus of propafenone (2 mg/kg, IV over 15 minutes). If atrial fibrillation persisted after 20 minutes, a continuous infusion of propafenone (7 microg/kg/min) was given for 120 minutes. Before, during, and after treatment, plasma propafenone concentrations, hematologic and serum biochemical values, and electolyte concentrations analyses were determined and clinical signs were monitored. Surface ECGs were recorded. If propafenone treatment failed, quinidine sulfate was administered. Bolus and continuous infusion induced minimal adverse effects. During the 15-minute bolus administration, a slight increase in heart rate was observed and horses appeared more sensitive to external stimuli. Throughout treatment, no significant changes were observed in respiratory rate, QRS or corrected QT duration, or results of hematologic analyses. Although a significant increase in F-wave interval and atrial fibrillation cycle length was observed and plasma propafenone concentrations (569 to 1,268 ng/mL) reached the human therapeutic range (64 to 1,044 ng/mL), none of the horses cardioverted to sinus rhythm. Sinus rhythm could be restored in all horses via standard oral administration of quinidine. A slow IV bolus of 2 mg of propafenone/kg followed by a continuous infusion of 7 microg/kg/min over 2 hours was not an effective treatment for chronic atrial fibrillation in horses.

Inhibitory Effects of Ketoconazole, Cimetidine and Erythromycin on Hepatic CYP3A Activities in Cats

Inhibitory effects of ketoconazole (KTZ), cimetidine (CIM), and erythromycin (ERY) were examined on CYP3A activities. Midazolam 1'- and 4-hydroxylation (MDZ1'H and MDZ4H) were used to determine CYP3A activities in hepatic microsomes obtained from cats (n=4). The results showed that, all the examined drugs inhibited the reactions in a noncompetitive manner. The inhibitory constants (Ki) of KTZ were 2.80 +/- 0.70 and 115 +/- 28 microM for MDZ1'H and MDZ4H, respectively. Those of CIM were 3.13 and 3.27 mM and of ERY were 3.14 and 6.41 mM for MDZ1'H and MDZ4H, respectively. Mechanism-based inhibition was also examined in this study. KTZ significantly reduced MDZ reactions in a time-dependent manner; while CIM and ERY did not. Also, the effects of KTZ and CIM on the pharmacokinetics of quinidine (QUN) were studied. KTZ or CIM (10 mg/kg/day, for one week) was given orally to cats (n=5). QUN (2 mg/kg, i. v.) was injected 2 hr after the last dose of KTZ or CIM. The analysis of the obtained pharmacokinetic parameters showed that, KTZ significantly reduced total body clearance of QUN by 35%, while CIM did not. These results suggest that, KTZ inhibits CYP3A activities (both in vitro and in vivo), but CIM does not. In clinical practice, therefore, KTZ may result in inhibition based drug-drug interaction with CYP3A substrates in cat patients, whereas CIM and ERY are unlikely to lead to interaction involving CYP3A substrates.

Termination of equine atrial fibrillation by quinidine: An optical mapping study

Objective To perform the first optical mapping studies of equine atrium to assess the spatiotemporal dynamics of atrial fibrillation (AF) and of its termination by quinidine. Animals Intact, perfused atrial preparations obtained from four horses with normal cardiovascular examinations. Materials and methods AF was induced by a rapid pacing protocol with or without acetylcholine perfusion, and optical mapping was used to determine spatial dominant frequency distributions, electrical activity maps, and single-pixel optical signals. Following induction of AF, quinidine gluconate was perfused into the preparation and these parameters were monitored during quinidine-induced termination of AF. Results Equine AF develops in the context of spatial gradients in action potential duration (APD) and diastolic interval (DI) that produce alternans, conduction block, and Wenckebach conduction in different regions at fast pacing rates. Quinidine terminates AF and prevents subsequent reinduction by reducing the maximal frequency and increasing frequency homogeneity. Conclusions Heterogeneity of APD and DI promote alternans and conduction block at fast pacing rates in the equine atrium, predisposing to the development of AF. Quinidine terminates AF by reducing maximum frequency and increasing frequency homogeneity. Our results are consistent with the hypothesis that quinidine increases effective refractory period, thereby decreasing frequency.

Therapeutic Strategies in Congenital Myasthenic Syndromes

Congenital myasthenic syndromes (CMS) are classified in terms of the located defect: presynaptic, postsynaptic, and synaptic. They are inherited disorders caused by various genetic defects, all but the slow-channel CMS by recessive inheritance. To date, 10 different CMS are known and further CMS subtypes and their genetic cause may be disclosed by future investigations. Prognosis in CMS is variable and largely depends on the pathophysiological and genetic defect. Subtypes showing progression and life-threatening crises with apneas are generally less favorable than others. Therapeutic agents used in CMS depend on the underlying defect and include acetylcholinesterase inhibitor, 3,4-diaminopyridine, quinidine sulfate, fluoxetine, acetazolamide, and ephedrine. Although there are no double-blind, placebo-controlled clinical trials for CMS, several drugs have shown convincingly positive clinical effects. It is therefore necessary to start a rational therapy regime as early as possible. In most CMS, however, mild and severe clinical courses are reported, which makes assessment on an individual basis necessary. This review emphasizes therapeutic strategies in CMS.

Brain levels of dextromethorphan and the intensity of opioid withdrawal in mice

Consistent with their antagonistic actions at N-methyl- d-aspartate type glutamate receptors, dextromethorphan (DXM) and its metabolite, dextrorphan (DXT) decrease the intensity of opioid withdrawal syndrome. Since quinidine (QND) affects CYP2D6-mediated metabolism and P-glycoprotein governed transport, we sought to determine whether co-treatment with QND would affect brain levels of DXM and DXT as well as the effect of these compounds on opioid withdrawal syndrome in mice. We found that DXM dose dependently inhibited the intensity of opioid withdrawal syndrome and that there was a tendency for a further decrease when QND was co-administered with DXM. Administration of 30 mg/kg of DXM resulted in higher brain levels of DXM and DXT than administration of 10 mg/kg of DXM, but much lower DXT levels than that produced by 30 mg/kg of DXT. Co-treatment with QND resulted in higher brain levels of DXM (but not DXT) suggesting that QND produces an increase in the brain availability of DXM. In summary, brain levels of DXM were inversely correlated with the intensity of opioid withdrawal syndrome. QND induced increased brain levels of DXM tend to attenuate the intensity of opioid withdrawal syndrome. We suggest that it is DXM, rather than DXT, that is responsible for the attenuating effect on the intensity of opioid withdrawal syndrome, and that the beneficial action of QND on the effect of DXM should be more pronounced in humans.

Pseudobulbar Palsy and Affect in a Case of Progressive Multifocal Leukoencephalopathy

Back to table of contents Previous article Next article LETTERFull AccessPseudobulbar Palsy and Affect in a Case of Progressive Multifocal LeukoencephalopathyKelly C. Graham M.D., M.S.David R. Spiegel M.D.,Kelly C. Graham M.D., M.S.Search for more papers by this authorDavid R. Spiegel M.D.Search for more papers by this author,Published Online:1 Jan 2008AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Pseudobulbar palsy, with its neuropsychiatric manifestation of pathological laughing and crying or pseudobulbar affect, has been described in a variety of CNS illnesses. 1 We present, with interest, a case of Pseudobulbar palsy in a patient with progressive multifocal leukoencephalopathy, a complication of AIDS. 2Case ReportOur patient is a 39-year-old African American male whom we were asked to evaluate at our teaching hospital for an acute change of mental status. The patient’s past medical history was significant for AIDS.On initial presentation, vital signs and physical examination were essentially within normal limits. However, his neurological examination was significant for bilateral upper extremity hyperreflexia; lower extremity reflexes were difficult to elicit due to the patient’s supine position. He had a positive babinski sign on the right and down-going toes on the left. The jaw-jerk reflex and gag reflex were slightly increased.Our patient was treated for metabolic abnormalities and his mental status improved minimally. The patient received a magnetic resonance imaging (MRI) scan of the head which demonstrated several patches of signal abnormality involving subcortical white matter, brainstem, and cerebellum. The most likely diagnosis was postviral related demyelination due progressive multifocal leukoencephalopathy.His psychiatric examination was significant for monotone, nasal speech. His affect was labile and he would easily burst into tears and laugh inappropriately to questions. Cognitively, the patient was oriented times one. His working and short-term memory were impaired.In addition to a nasal dysarthria, our patient also experienced dysphagia. A barium swallow demonstrated aspiration of all consistency liquids. However, there were no abnormalities in relevant anatomy.Nonetheless, our patient’s medical condition worsened, and unfortunately he expired before we could attempt treatment of his pseudobulbar affect.Discussion This case demonstrates a clinical picture of pseudobulbar palsy in a patient suffering from progressive multifocal leukoencephalopathy due to AIDS. Given our patient’s clinical symptoms, plus pseudobulbar affect and MRI findings, he seemed to have pseudobulbar palsy. Historically, pseudobulbar palsy is considered in the setting of vascular disorders, neurodegenerative disorders, and other CNS diseases. 1 While various lesions of the CNS may present with pseudobulbar palsy, typically corticobulbar fibers are involved. 1 Similar to our patient’s MRI, progressive multifocal leukoencephalopathy includes multiple areas of demyelination, 3 further substantiating our impression of pseudobulbar palsy. Two predominate mechanisms have been proposed to explain pseudobulbar affect. One suggests disinhibition of the motor neurons controlling laughter and crying. Newer research suggests a reciprocal pathway exists between the cerebellum and the brainstem that adjusts laughter and crying responses, making them appropriate to context. 4 Pharmacologic interventions for pseudobulbar affect include the tricyclic antidepressants, serotonin reuptake inhibitors and a novel approach utilizing dextromethorphan and quinidine sulfate. Dextromethorphan, an N -methyl-D-aspartate receptor antagonist, inhibits glutamatergic transmission in the regions of the brainstem and cerebellum, which are hypothesized to be involved in pseudobulbar symptoms. Dextromethorphan acts as a sigma ligand, binding to the sigma-1 receptors that mediate the emotional motor expression. 5We feel this case report illustrates that pseudobulbar palsy and pseudobulbar affect should be considered across a variety of CNS conditions.Department of Psychiatry, Eastern Virginia Medical School, Norfolk, VirginiaReferences1 . Moore D, Jefferson J: Pseudobulbar palsy, in Handbook of Medical Psychiatry, 2nd ed. Mosby, 2004, pp 302–303Google Scholar2 . Mamidi A, DeSimone J, Pomerantz R: Central nervous system infections in individuals with HIV-1 infection. J Neurovirol 2002; 8:158–167Google Scholar3 . Mark A, Atlas S: Progressive multifocal leukoencephalopathy in patients with AIDS: appearance on MR images. Radiology 1989; 173:517–529Google Scholar4 . Keister GW: Pseudobulbar affect: keys to its cause and management. Applied Neurology 2006; 2(8)Google Scholar5 . Brooks BR, Thisted RA, Appel SH, et al: Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology 2004; 63:1364–1370Google Scholar FiguresReferencesCited byDetailsCited byTreatment of pseudobulbar affect with citalopram in a patient with progressive multifocal leukoencephalopthyJournal of Clinical Neuroscience, Vol. 19, No. 1Pseudobulbar PalsyAmyotrophic Lateral Sclerosis, Vol. 11, No. 1-2 Volume 20Issue 1 Winter, 2008Pages 110-111 Metrics PDF download History Published online 1 January 2008 Published in print 1 January 2008

Pseudobulbar Palsy and Affect in a Case of Progressive Multifocal Leukoencephalopathy

Back to table of contents Previous article Next article LETTERFull AccessPseudobulbar Palsy and Affect in a Case of Progressive Multifocal LeukoencephalopathyKelly C. Graham M.D., M.S.David R. Spiegel M.D.,Kelly C. Graham M.D., M.S.Search for more papers by this authorDavid R. Spiegel M.D.Search for more papers by this author,Published Online:1 Jan 2008AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Pseudobulbar palsy, with its neuropsychiatric manifestation of pathological laughing and crying or pseudobulbar affect, has been described in a variety of CNS illnesses. 1 We present, with interest, a case of Pseudobulbar palsy in a patient with progressive multifocal leukoencephalopathy, a complication of AIDS. 2Case ReportOur patient is a 39-year-old African American male whom we were asked to evaluate at our teaching hospital for an acute change of mental status. The patient’s past medical history was significant for AIDS.On initial presentation, vital signs and physical examination were essentially within normal limits. However, his neurological examination was significant for bilateral upper extremity hyperreflexia; lower extremity reflexes were difficult to elicit due to the patient’s supine position. He had a positive babinski sign on the right and down-going toes on the left. The jaw-jerk reflex and gag reflex were slightly increased.Our patient was treated for metabolic abnormalities and his mental status improved minimally. The patient received a magnetic resonance imaging (MRI) scan of the head which demonstrated several patches of signal abnormality involving subcortical white matter, brainstem, and cerebellum. The most likely diagnosis was postviral related demyelination due progressive multifocal leukoencephalopathy.His psychiatric examination was significant for monotone, nasal speech. His affect was labile and he would easily burst into tears and laugh inappropriately to questions. Cognitively, the patient was oriented times one. His working and short-term memory were impaired.In addition to a nasal dysarthria, our patient also experienced dysphagia. A barium swallow demonstrated aspiration of all consistency liquids. However, there were no abnormalities in relevant anatomy.Nonetheless, our patient’s medical condition worsened, and unfortunately he expired before we could attempt treatment of his pseudobulbar affect.Discussion This case demonstrates a clinical picture of pseudobulbar palsy in a patient suffering from progressive multifocal leukoencephalopathy due to AIDS. Given our patient’s clinical symptoms, plus pseudobulbar affect and MRI findings, he seemed to have pseudobulbar palsy. Historically, pseudobulbar palsy is considered in the setting of vascular disorders, neurodegenerative disorders, and other CNS diseases. 1 While various lesions of the CNS may present with pseudobulbar palsy, typically corticobulbar fibers are involved. 1 Similar to our patient’s MRI, progressive multifocal leukoencephalopathy includes multiple areas of demyelination, 3 further substantiating our impression of pseudobulbar palsy. Two predominate mechanisms have been proposed to explain pseudobulbar affect. One suggests disinhibition of the motor neurons controlling laughter and crying. Newer research suggests a reciprocal pathway exists between the cerebellum and the brainstem that adjusts laughter and crying responses, making them appropriate to context. 4 Pharmacologic interventions for pseudobulbar affect include the tricyclic antidepressants, serotonin reuptake inhibitors and a novel approach utilizing dextromethorphan and quinidine sulfate. Dextromethorphan, an N -methyl-D-aspartate receptor antagonist, inhibits glutamatergic transmission in the regions of the brainstem and cerebellum, which are hypothesized to be involved in pseudobulbar symptoms. Dextromethorphan acts as a sigma ligand, binding to the sigma-1 receptors that mediate the emotional motor expression. 5We feel this case report illustrates that pseudobulbar palsy and pseudobulbar affect should be considered across a variety of CNS conditions.Department of Psychiatry, Eastern Virginia Medical School, Norfolk, VirginiaReferences1 . Moore D, Jefferson J: Pseudobulbar palsy, in Handbook of Medical Psychiatry, 2nd ed. Mosby, 2004, pp 302–303Google Scholar2 . Mamidi A, DeSimone J, Pomerantz R: Central nervous system infections in individuals with HIV-1 infection. J Neurovirol 2002; 8:158–167Google Scholar3 . Mark A, Atlas S: Progressive multifocal leukoencephalopathy in patients with AIDS: appearance on MR images. Radiology 1989; 173:517–529Google Scholar4 . Keister GW: Pseudobulbar affect: keys to its cause and management. Applied Neurology 2006; 2(8)Google Scholar5 . Brooks BR, Thisted RA, Appel SH, et al: Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology 2004; 63:1364–1370Google Scholar FiguresReferencesCited byDetailsCited ByPseudobulbar PalsyAmyotrophic Lateral Sclerosis, Vol. 11, No. 1-2 Volume 20Issue 1 Winter, 2008Pages 110-111 Metrics PDF download History Published online 1 January 2008 Published in print 1 January 2008

ブルガダ症候群での心室細動誘発に対するキニジン静脈内投与による抑制効果

ブルガダ症候群での心室細動誘発に対するキニジン静脈内投与による抑制効果

A Brugada syndrome case with electrical storm successfully treated by the increasing of the quinidine sulfate dose

A Brugada syndrome case with electrical storm successfully treated by the increasing of the quinidine sulfate dose