RESUMO
Tocainide is an antiarrhythmic agent belonging to class IB that was primarily used for suppression of symptomatic ventricular arrhythmias. Tocainide was also reported to relieve pain such as tic douloureux, trigemina neuralgia in humans and tinnitus. Significant antinociception, as assayed on the hot-plate test, was observed after intraperitoneal injection of tocainide, too. By the mid-1980s tocainide was emerging as a more consistently effective treatment for myotonic disorders. Numerous reports of serious adverse reactions led to the use of tocainide being discontinued, even though research on tocainide and its analogues, endowed with a better pharmacological profile, is still in progress for their potential usefulness in the treatment of myotonias. This review is focused on the description of the different synthetic routes to racemic and optically active tocainide developed in the last decades, as well as analytical studies regarding enantioseparation methods. Finally, some analogues of tocainide reported in the literature, most of which with pharmacological studies, have been mentioned.
Assuntos
Antiarrítmicos/síntese química , Tocainide/análogos & derivados , Antiarrítmicos/farmacocinética , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Meia-Vida , Humanos , Canal de Sódio Disparado por Voltagem NAV1.4/química , Canal de Sódio Disparado por Voltagem NAV1.4/metabolismo , Relação Quantitativa Estrutura-Atividade , Tocainide/farmacocinética , Tocainide/uso terapêutico , Bloqueadores do Canal de Sódio Disparado por Voltagem/síntese química , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacocinética , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêuticoRESUMO
Although the sodium channel blocker, mexiletine, is the first choice drug in myotonia, some myotonic patients remain unsatisfied due to contraindications, lack of tolerability, or incomplete response. More therapeutic options are thus needed for myotonic patients, which require clinical trials based on solid preclinical data. In previous structure-activity relationship studies, we identified two newly-synthesized derivatives of tocainide, To040 and To042, with greatly enhanced potency and use-dependent behavior in inhibiting sodium currents in frog skeletal muscle fibers. The current study was performed to verify their potential as antimyotonic agents. Patch-clamp experiments show that both compounds, especially To042, are greatly more potent and use-dependent blockers of human skeletal muscle hNav1.4 channels compared to tocainide and mexiletine. Reduced effects on F1586C hNav1.4 mutant suggest that the compounds bind to the local anesthetic receptor, but that the increased hindrance and lipophilia of the N-substituent may further strengthen drug-receptor interaction and use-dependence. Compared to mexiletine, To042 was 120 times more potent to block hNav1.4 channels in a myotonia-like cellular condition and 100 times more potent to improve muscle stiffness in vivo in a previously-validated rat model of myotonia. To explore toxicological profile, To042 was tested on hERG potassium currents, motor coordination using rotarod, and C2C12 cell line for cytotoxicity. All these experiments suggest a satisfactory therapeutic index for To042. This study shows that, owing to a huge use-dependent block of sodium channels, To042 is a promising candidate drug for myotonia and possibly other membrane excitability disorders, warranting further preclinical and human studies.
Assuntos
Miotonia/prevenção & controle , Canal de Sódio Disparado por Voltagem NAV1.4/fisiologia , Tocainide/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Animais , Relação Dose-Resposta a Droga , Canais de Potássio Éter-A-Go-Go/fisiologia , Humanos , Masculino , Mexiletina/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Miotonia/fisiopatologia , Ratos , Ratos Wistar , Reflexo de Endireitamento/efeitos dos fármacos , Teste de Desempenho do Rota-Rod , Tocainide/efeitos adversos , Tocainide/análogos & derivados , Tocainide/uso terapêutico , Bloqueadores do Canal de Sódio Disparado por Voltagem/efeitos adversos , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêuticoRESUMO
BACKGROUND: Trigeminal neuralgia was defined by the International Association for the Study of Pain as a sudden, usually unilateral, severe, brief, stabbing recurrent pain in the distribution of one or more branches of the fifth cranial nerve. Standard treatment is with anti-epileptic drugs. Non-antiepileptic drugs have been used in the management of trigeminal neuralgia since the 1970s. This is an update of a review first published in 2006 and previously updated in 2011. OBJECTIVES: To systematically review the efficacy and tolerability of non-antiepileptic drugs for trigeminal neuralgia. SEARCH METHODS: On 20 May 2013, for this updated review, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2013, Issue 4), MEDLINE (January 1966 to May 2013), EMBASE (January 1980 to May 2013), LILACS (January 1982 to May 2013) and the Chinese Biomedical Retrieval System (1978 to May 2013). We searched clinical trials registries for ongoing trials. SELECTION CRITERIA: We included double-blind, randomised controlled trials in which the active drug was used either alone or in combination with other non-antiepileptic drugs for at least two weeks. DATA COLLECTION AND ANALYSIS: Two authors decided which trials fitted the inclusion criteria and independently graded risk of bias. We assessed the quality of the evidence according to the GRADE criteria for this update. MAIN RESULTS: In this 2013 update, we updated the searches, but identified only two new ongoing studies. The review includes four trials involving 139 participants. The primary outcome measure in each was pain relief. Three trials compared one of the oral non-antiepileptic drugs tizanidine, tocainide or pimozide with carbamazepine. The quality of evidence for all outcomes for which data were available was low. In a trial of tizanidine involving 12 participants (one dropped out due to unrelated disease), one of five participants treated with tizanidine and four of six treated with carbamazepine improved (risk ratio (RR) 0.30, 95% confidence interval (CI) 0.05 to 1.89). Few side effects were noted with tizanidine. For pimozide, there was evidence of greater efficacy than carbamazepine at six weeks. Up to 83% of participants reported adverse effects but these did not lead to withdrawal; the report did not provide comparable data for carbamazepine. Limited data meant that we could not assess the effects of tocainide; however, data from non-randomised studies (not included in this review) indicate that serious haematological adverse events can occur. A trial involving 47 participants compared 0.5% proparacaine hydrochloride eyedrops with placebo but did not show any significant benefits, again according to low-quality evidence. The report did not mention adverse events. The proparacaine trial was at low risk of bias; the other trials were at unclear risk of bias overall. AUTHORS' CONCLUSIONS: There is low-quality evidence that the effect of tizanidine is not significantly different than that of carbamazepine in treating trigeminal neuralgia. Pimozide is more effective than carbamazepine, although the evidence is of low quality and the data did not allow comparison of adverse event rates. There is also low-quality evidence that 0.5% proparacaine hydrochloride eye drops have no benefit over placebo. Limitations in the data for tocainide prevent any conclusions being drawn. There is insufficient evidence from randomised controlled trials to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia. More research is needed.
Assuntos
Analgésicos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Neuralgia do Trigêmeo/tratamento farmacológico , Amitriptilina/uso terapêutico , Baclofeno/uso terapêutico , Carbamazepina/uso terapêutico , Clomipramina/uso terapêutico , Clonidina/análogos & derivados , Clonidina/uso terapêutico , Humanos , Pimozida/uso terapêutico , Propoxicaína/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tocainide/uso terapêuticoRESUMO
OBJECTIVE: Controversy exists about the effectiveness of anticonvulsants for the management of orofacial pain disorders. To ascertain appropriate therapies, a systematic review was conducted of existing randomized controlled trials. STUDY DESIGN: Trials were identified from PubMed, Cochrane, and Ovid Medline databases from 1962 through March 2010, from references in retrieved reports, and from references in review articles. Eight useful trials were identified for this review. Six studies were randomized placebo-controlled trials and 2 studies were randomized active-controlled. Two independent investigators reviewed these articles by using a 15-item checklist. RESULTS: Four studies were classified as "high quality." However, heterogeneity of the trials and the small sample sizes precluded the drawing of firm conclusions about the efficacy of the interventions studied on orofacial pain patients. CONCLUSIONS: There is limited to moderate evidence supporting the efficacy of commonly used anticonvulsants for treatment of patients with orofacial pain disorders. More randomized controlled trials are needed on the efficacy of anticonvulsants.
Assuntos
Anticonvulsivantes/uso terapêutico , Dor Facial/tratamento farmacológico , Neuralgia do Trigêmeo/tratamento farmacológico , Aminas/uso terapêutico , Síndrome da Ardência Bucal/tratamento farmacológico , Carbamazepina/uso terapêutico , Clonazepam/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Gabapentina , Humanos , Lamotrigina , Músculos da Mastigação/fisiopatologia , Pimozida/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tocainide/uso terapêutico , Triazinas/uso terapêutico , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
BACKGROUND: Non-antiepileptic drugs have been used in the management of trigeminal neuralgia since the 1970s. OBJECTIVES: The objective was to systematically review the efficacy and tolerability of non-antiepileptic drugs for trigeminal neuralgia. SEARCH STRATEGY: For this updated review we searched the Cochrane Neuromuscular Disease Group Specialized Register (30 April 2010). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), MEDLINE (January 1966 to April 2010), EMBASE (January 1980 to April 2010), LILACS (January 1982 to April 2010) and the Chinese Biomedical Retrieval System (1978 to April 2010). We handsearched 10 Chinese journals. SELECTION CRITERIA: We searched for double-blind randomized or quasi-randomized controlled trials in which the active drug was used for at least two weeks. DATA COLLECTION AND ANALYSIS: Two authors decided which trials fitted the inclusion criteria and independently graded risk of bias. MAIN RESULTS: Four trials involving 139 participants were included. The primary outcome measure in each was pain relief. Three trials with an unclear risk of bias compared one of the non-antiepileptic drugs tizanidine, tocainide or pimozide with carbamazepine. In a trial of tizanidine involving 12 participants (one dropped out due to unrelated disease) one of five treated with tizanidine and four of six treated with carbamazepine improved, risk ratio 0.30 (95% CI 0.05 to 1.89). Few side effects were noted with tizanidine. In a study involving 12 participants there was an improvement in mean pain scores with tocainide similar to that with carbamazepine, but significant side effects limited its use. In the pimozide study more participants improved on pimozide (48/48) than with carbamazepine (27/48) (risk ratio 1.76, 95% CI 1.37 to 2.26). Up to 83% of participants reported adverse effects but these did not lead to withdrawal from the study. A trial with low risk of bias involving 47 participants compared 0.5% proparacaine hydrochloride eyedrops with placebo but did not show any significant benefits or side effects. AUTHORS' CONCLUSIONS: Of the four studies identified, one had low and three an unclear risk of bias. There is insufficient evidence from randomized controlled trials to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia. More research is needed.
Assuntos
Analgésicos/uso terapêutico , Neuralgia do Trigêmeo/tratamento farmacológico , Amitriptilina/uso terapêutico , Baclofeno/uso terapêutico , Carbamazepina/uso terapêutico , Clomipramina/uso terapêutico , Clonidina/análogos & derivados , Clonidina/uso terapêutico , Humanos , Pimozida/uso terapêutico , Propoxicaína/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tocainide/uso terapêuticoRESUMO
The role of voltage-gated sodium channels in the transmission of neuropathic pain is well recognized. For instance, genetic evidence recently indicate that the human Nav1.7 sodium channel subtype plays a crucial role in the ability to perceive pain sensation and may represent an important target for analgesic/anti-hyperalgesic drugs. In this study a newly synthesized tocainide congener, named NeP1, was tested in vitro on recombinant hNav1.4 and hNav1.7 channels using patch-clamp technique and, in vivo, in two rat models of persistent neuropathic pain obtained either by chronic constriction injury of the sciatic nerve or by oxaliplatin treatment. NeP1 efficiently blocked hNav1.4 and hNav1.7 channels in a dose- and use-dependent manner, being by far more potent than tocainide. Importantly, the new compound displayed a remarkable use-dependent effect, which likely resulted from a very high affinity for inactivated compared to closed channels. In both models of neuropathic pain, NeP1 was greatly more potent than tocainide in reverting the reduction of pain threshold in vivo. In oxaliplatin-treated rats, NeP1 even produced greater and more durable anti-hyperalgesia than the reference drug tramadol. In addition, in vivo and in vitro studies suggest a better toxicological and pharmacokinetic profile for NeP1 compared to tocainide. Overall, these results indicate NeP1 as a new promising lead compound for further development in the treatment of chronic pain of neuropathic origin.
Assuntos
Analgésicos/farmacologia , Dor/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Bloqueadores dos Canais de Sódio/farmacologia , Canais de Sódio/fisiologia , Tocainide/análogos & derivados , Tocainide/farmacologia , Analgésicos/uso terapêutico , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Hiperalgesia/tratamento farmacológico , Masculino , Proteínas Musculares/antagonistas & inibidores , Canal de Sódio Disparado por Voltagem NAV1.4 , Canal de Sódio Disparado por Voltagem NAV1.7 , Técnicas de Patch-Clamp , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Albumina Sérica/metabolismo , Bloqueadores dos Canais de Sódio/uso terapêutico , Tocainide/uso terapêuticoRESUMO
BACKGROUND: Non-antiepileptic drugs have been used in trigeminal neuralgia management since the 1970s. OBJECTIVES: The objective was to review systematically the efficacy of non-antiepileptic drugs for trigeminal neuralgia. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Register, MEDLINE, EMBASE, and LILACS (all to August 2005) and the Chinese Biomedical Retrieval System, the database of the Chinese Cochrane Center (The Cochrane Library, Issue 1 2005), conference paper databases and checked bibliographies. We handsearched ten Chinese journals. SELECTION CRITERIA: We searched for randomized or quasi-randomized controlled trials. DATA COLLECTION AND ANALYSIS: Two authors decided which trials fitted the inclusion criteria and graded methodological quality independently. MAIN RESULTS: Nine trials of different non-antiepileptic drugs involving 223 participants were included. Each trial investigated one non-antiepileptic drug. Two trials tested baclofen. In one, more people gained 50% reduction from baseline than with placebo (relative risk 15.00, 95% CI 0.97 to 231.84, P value = 0.05). In the other, slightly more participants on baclofen had a 75% reduction in attacks on the 10th day compared with carbamazepine (relative risk 2.38, 95% CI 0.83 to 6.85, P value = 0.11). One trial showed no significant difference in reduction in average daily frequency of attacks with L-Baclofen compared with racemic baclofen. Tizanidine was investigated in two trials. In one, the proportion of people with reduction in the average number of paroxysms per day increased with tizanidine compared with placebo (relative risk 8.00, 95% CI 1.21 to 52.69, P value = 0.03). In the other, one of five participants improved in visual analog scale score with tizanidine and four of six with carbamazepine (relative risk 0.30, 95% CI 0.05 to 1.89, P value = 0.20). One study showed that the improvement in mean values of pain scores with tocainide was similar to that of carbamazepine. In one study more participants improved during the pimozide than the carbamazepine period (relative risk 1.78, 95% CI 1.39 to 2.28). In one study, proparacaine hydrochloride 0.5% instillation into the eyes was not significantly different from placebo (relative risk 1.06, 95% CI 0.37 to 2.99, P value = 0.92). In another, there was moderate or marked improvement in seven of nine participants treated with clomipramine and three of nine with amitriptyline after a 12-week treatment (RR 2.33, 95% CI 0.87 to 6.27). AUTHORS' CONCLUSIONS: There is insufficient evidence from randomized controlled trials to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia. More research is needed.
Assuntos
Neuralgia do Trigêmeo/tratamento farmacológico , Amitriptilina/uso terapêutico , Baclofeno/uso terapêutico , Carbamazepina/uso terapêutico , Clomipramina/uso terapêutico , Clonidina/análogos & derivados , Clonidina/uso terapêutico , Humanos , Pimozida/uso terapêutico , Propoxicaína/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tocainide/uso terapêuticoRESUMO
JUSTIFICATIVA E OBJETIVOS: A neuralgia do trigêmeo é uma síndrome de dor crônica, caracterizada por paroxismos de dor excruciante que afeta de maneira dramática a qualidade de vida dos pacientes acometidos. A terapia medicamentosa sistêmica é considerada o tratamento de primeira linha para esta doença. Este estudo teve como objetivo avaliar a eficácia, a segurança e a tolerabilidade dos diversos tratamentos farmacológicos oferecidos aos pacientes com neuralgia do trigêmeo, visando fornecer evidências para as recomendações da prática clínica e identificar as necessidades de pesquisas adicionais. MÉTODO: Foram analisados ensaios clínicos aleatórios e controlados, publicados até julho de 2003, sobre o efeito analgésico das drogas prescritas no tratamento da neuralgia do trigêmeo. A análise estatística foi realizada com o auxilio do programa Review Manager 4.2.2 (Colaboração Cochrane, 2003). RESULTADOS: Os resultados da metanálise sugerem que a carbamazepina é mais eficaz que o placebo. Em três estudos controlados comparando a lamotrigina, o topiramato e o cloridrato de proparacaína ao placebo, somente a lamotrigina mostrou-se superior a ele. O dextrometafano foi comparado ao lorazepam em baixas doses, havendo aumento da dor com o uso daquele fármaco. Três estudos compararam a carbamazepina com a tizanidina, a tocainida e a pimozida, mostrando-se apenas a pimozida superior à carbamazepina. CONCLUSÕES: A carbamazepina continua como droga de escolha para o tratamento da neuralgia do trigêmeo, estando a lamotrigina e a pimozida indicadas em casos refratários à terapia convencional. Além disso, estudos adicionais são necessários para o estabelecimento de futuras opções terapêuticas.
Assuntos
Humanos , Neuralgia do Trigêmeo/tratamento farmacológico , Carbamazepina/uso terapêutico , Pimozida/uso terapêutico , Tocainide/uso terapêutico , Lamotrigina/uso terapêutico , Topiramato/uso terapêutico , Lorazepam/uso terapêuticoRESUMO
The antimyotonic activity of chiral derivatives of mexiletine and tocainide, selected as potent use-dependent blockers of skeletal muscle sodium channels, was evaluated in vivo acutely in myotonic ADR mice. The compounds had either aromatic (Me4 and Me6) or branched isopropyl groups (Me5 and To1) on the asymmetric centre, or had this latter one methylene apart from the amino group (Me2). Therapeutic doses of mexiletine (5-10 mg/kg) and tocainide (7-20 mg/kg) significantly reduced the long time of righting reflex (TRR), typical of ADR mice. Me4, Me5 and Me6 were 2-fold more potent than mexiletine. To1 fully normalised the TRR at 7 mg/kg. The electromyographic analysis confirmed a muscle-based activity for drug effectiveness on TRR. All the compounds reduced the myotonic hyperexcitability of intercostal muscle fibres when tested in vitro by current-clamp recordings, with a potency correlated with their action on sodium channels. On stimulus-evoked firing, the isopropyl analogues were 2-4-fold more potent than parent compounds, while the aromatic analogues were about 10-fold more potent than mexiletine. Patch-clamp recordings confirmed a normal-like pharmacological sensitivity of sodium channels of native ADR muscle fibres. Finally, the in vivo antimyotonic activity is due to the block of sodium channels and divergences with in vitro potency can be related to structure-based changes in drug pharmacokinetics.
Assuntos
Antiarrítmicos/uso terapêutico , Mexiletina/uso terapêutico , Transtornos Miotônicos/tratamento farmacológico , Tocainide/uso terapêutico , Potenciais de Ação/efeitos dos fármacos , Análise de Variância , Animais , Antiarrítmicos/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Condutividade Elétrica , Eletromiografia/métodos , Feminino , Técnicas In Vitro , Concentração Inibidora 50 , Masculino , Mexiletina/sangue , Camundongos , Camundongos Mutantes , Contração Muscular/efeitos dos fármacos , Transtornos Miotônicos/sangue , Técnicas de Patch-Clamp/métodos , Canais de Sódio/efeitos dos fármacos , Canais de Sódio/fisiologia , Relação Estrutura-Atividade , Fatores de Tempo , Tocainide/análogos & derivados , Tocainide/sangueRESUMO
Las arritmias cardíacas son comunes en los pacientes críticos, pudiendo ser benignas, en un comienzo, o fatales. Requieren de un diagnóstico rápido y exacto. Los intensivistas debemos estar familiarizados con su rápida identificación y manejo para una buena práctica clínica. Presentamos el caso de una mujer de 86 años, con antecedentes de Diabetes Mellitus II B e hipertensión arterial que ingresó a nuestra clínica con una neumonía basal derecha y brusca falla respiratoria, cuyo ecocardiograma muestra mínima insuficiencia aórtica, mitral y tricuspídea, con función sistólica global-segmentaria conservadas y cuya tomografía axial computada de tórax con énfasis vascular descartó tromboembolismo. Durante su evolución hospitalaria presentó arritmia extrasistólica supraventricular, fibrilación auricular, taquicardia ventricular y fibrilación ventricular, las que unidas a cambios electrocardiográficos, QT corregido de 714 mseg y troponina T de 0,018 llevaron al estudio coronario, demostrando su origen isquémico. Se analizan los electrocardiogramas y se discute el diagnóstico diferencial etiológico.
Assuntos
Humanos , Feminino , Idoso , Antiarrítmicos/uso terapêutico , Eletrocardiografia , Síndrome do QT Longo/cirurgia , Síndrome do QT Longo/tratamento farmacológico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Angioplastia , Diabetes Mellitus Tipo 2 , Isoproterenol/uso terapêutico , Fatores de Risco , Tocainide/uso terapêuticoAssuntos
Miotonia , Cromossomos Humanos Par 7 , Diagnóstico Diferencial , Éxons/genética , Genes Dominantes , Humanos , Mexiletina/uso terapêutico , Mutação , Miotonia/genética , Miotonia/fisiopatologia , Prognóstico , Bloqueadores dos Canais de Sódio/uso terapêutico , Canais de Sódio/genética , Tocainide/uso terapêuticoRESUMO
BACKGROUND: Andersen syndrome is a rare form of periodic paralysis (PP) associated with dysmorphic features and potentially fatal cardiac dysrhythmias. To date, no electrodiagnostic abnormalities have been reported that can be used to confirm the presence of PP in this condition. OBJECTIVES: To determine if the exercise test could be used to confirm the diagnosis of PP in Andersen syndrome. To evaluate the exercise test as a means to assess neuromuscular status during treatment. METHODS: We performed the exercise test on 2 patients with Andersen syndrome. In 1 patient, we used a modified version of the test to document responsiveness to treatment with tocainide. RESULTS: Studies in both patients demonstrated a progressive decline in the compound muscle action potential amplitude after exercise that was characteristic of the phenomenon seen in other forms of PP. In 1 patient, improvement in interattack strength and a reduction in the number of attacks of weakness correlated with improvement in the test results. CONCLUSIONS: Our cases demonstrate that the exercise test can confirm the diagnosis of PP in Andersen syndrome. A modified version of exercise testing may also be considered as an objective method for documenting treatment responses in PP.
Assuntos
Síndrome do QT Longo/diagnóstico , Paralisias Periódicas Familiares/diagnóstico , Anormalidades Múltiplas , Potenciais de Ação , Adolescente , Adulto , Antiarrítmicos/uso terapêutico , Teste de Esforço , Ossos Faciais/anormalidades , Feminino , Humanos , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/etiologia , Masculino , Debilidade Muscular , Tocainide/uso terapêuticoRESUMO
Neuralgia of the trigeminus (NT) is the most common of cranial nerve neuralgias. Its diagnosis is entirely clinical and its most common form of presentation is well understood. Questions of differential diagnosis can emerge with certain entities such as atypical trigeminal neuralgia, short-duration unilateral neuralgiform cephalea of the trigeminus (SUNCT) arising from injection to the conjunctival, lacrimal or other glands, cluster headache, chronic paroxymal hemicrania, pain arising in the teeth and myofacial pain syndrome. The three main causative factors of NT are compression of the nerve root by an artery in the prepontine space, thereby creating an area of demyelinization, compression of the nerve by a tumor, and multiple sclerosis. The first is the most common of the three. NT can be classified as essential in 10 to 30% of patients. Recent advances in magnetic resonance (MR), and its advantages over other imaging systems, have made MR the diagnostic method of choice. The first treatment is medical and the basic drugs involved can be considered classic. Other therapies have been suggested in recent years, however, and should probably be studied further. Two substances stand out among those proposed: tocainide, an antiarrhythmic drug, and pimozide, an antipsychotic. Surgical treatment of NT can address either the cause (tumor or vascular compression) or symptoms, the latter being indicated when medical treatment fails. Surgery can be performed on peripheral nerves, on the gasserian ganglion and on the posterior fossa. The indications, outcomes and possible complications are quite different for each approach, making choice controversial.
Assuntos
Pimozida/uso terapêutico , Tocainide/uso terapêutico , Neuralgia do Trigêmeo , Adolescente , Adulto , Idoso , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Antiarrítmicos/uso terapêutico , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Fossa Craniana Posterior/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Relaxantes Musculares Centrais/administração & dosagem , Relaxantes Musculares Centrais/efeitos adversos , Relaxantes Musculares Centrais/uso terapêutico , Nervos Periféricos/cirurgia , Pimozida/administração & dosagem , Pimozida/efeitos adversos , Rizotomia , Fatores Sexuais , Tocainide/administração & dosagem , Tocainide/efeitos adversos , Gânglio Trigeminal/cirurgia , Neuralgia do Trigêmeo/diagnóstico , Neuralgia do Trigêmeo/tratamento farmacológico , Neuralgia do Trigêmeo/cirurgiaAssuntos
Anestésicos Locais/administração & dosagem , Denervação , Lidocaína/administração & dosagem , Cuidados Pré-Operatórios , Nervo Isquiático/cirurgia , Automutilação/prevenção & controle , Tocainide/administração & dosagem , Anestésicos Locais/uso terapêutico , Animais , Injeções Espinhais , Lidocaína/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Ratos , Tocainide/uso terapêuticoRESUMO
Tocainide was administered to 23 cardiomyopathic Doberman Pinschers at doses of 15 to 25 mg/kg tid. These doses produced peak (2-hour) serum concentrations of 6.2 to 19.1 mg/L and trough (8-hour) serum concentrations of 2.3 to 11.1 mg/L. Anorexia and gastrointestinal disturbances occurred in 8 dogs (35%) at doses (15.6 to 25.0 mg/kg) that were not different from those (16.0 to 26.0 mg/kg) received by dogs that did not experience toxicity. Doses producing peak serum concentrations that were either greater or less than 14 mg/L were not different. Likewise, doses producing trough values that were either greater or less than 6 mg/L were not different. The mean dose that produced peak serum concentrations of 10 to 13.6 mg/L and trough concentrations of 4.2 to 10.0 mg/L was 17.9 mg/kg, and was associated with anorexia in 4 dogs. Mean peak serum concentrations associated with toxicity (14.4 mg/L) were significantly higher (P = .02) than dogs not experiencing toxicity (11.8 mg/L). Serious adverse effects occurred in 7 of 12 dogs (58%) receiving tocainide for longer than 4 consecutive months. Progressive corneal endothelial dystrophy occurred in 3 dogs. Although a causal effect could not be proven, 6 dogs experienced renal dysfunction during treatment. Drug doses in these 7 dogs were similar to those received by other dogs. At least a 70% reduction of the total numbers of ventricular premature contractions occurred in 80% of dogs treated, and ventricular tachycardia was eliminated in 90% of affected dogs by the time of the first posttreatment Holter recording. Long-term control of ventricular tachyarrhythmias was difficult to achieve in some dogs when the left ventricular shortening fraction was less than approximately 17%.
Assuntos
Antiarrítmicos/uso terapêutico , Cardiomiopatias/veterinária , Doenças do Cão , Taquicardia Ventricular/veterinária , Tocainide/uso terapêutico , Animais , Anorexia , Antiarrítmicos/efeitos adversos , Antiarrítmicos/sangue , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/fisiopatologia , Cães , Eletrocardiografia Ambulatorial/veterinária , Estudos Retrospectivos , Especificidade da Espécie , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/etiologia , Tocainide/efeitos adversos , Tocainide/sangueRESUMO
The effects of disopyramide, phenytoin, mexiletine, and tocainide were compared in 30 patients with myotonic disorders. The severity of myotonia was assessed by clinical and electromyographic criteria at the end of each treatment phase lasting four weeks. Mexiletine (MXT) and tocainide (TCD) were found to be the most potent antimyotonic agents. The antimyotonic efficacy of MXT and TCD is explained by their fast-blocking effect on voltage-dependent sodium channels in the muscle membrane. The benefits of myotonia control with pharmacological agents must be weight against the risk of therapy in the individual patient. Because of the risks of hematologic problems, TCD is not recommended by us for the treatment of myotonia.
Assuntos
Antiarrítmicos/uso terapêutico , Miotonia/tratamento farmacológico , Adolescente , Adulto , Disopiramida/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Eletrocardiografia/efeitos dos fármacos , Feminino , Humanos , Masculino , Mexiletina/uso terapêutico , Pessoa de Meia-Idade , Miotonia Congênita/tratamento farmacológico , Distrofia Miotônica/tratamento farmacológico , Exame Neurológico/efeitos dos fármacos , Fenitoína/uso terapêutico , Estudos Prospectivos , Método Simples-Cego , Tocainide/uso terapêuticoRESUMO
Antiarrhythmic treatment with single agents is often ineffective and can be limited by dose-dependent side-effects. Therefore, combinations of antiarrhythmic drugs in smaller and well-tolerated doses are advocated in cases refractory to single antiarrhythmic drugs. Basically, substances belonging to the same electrophysiologic class should not be combined. A combination of beta-adrenoreceptor blockers with class I antiarrhythmic drugs may be effective, mainly in cases in which the arrhythmia is dependent on adrenergic stimulation. As shown in our study, the combination of class III and I B-substances can be useful in some cases, from the electrophysiological and clinical points of view. Among the successful combinations of this type are amiodarone and mexiletine, sotalol and mexiletine, and sotalol and tocainide. In patients refractory to amiodarone alone or to a combination with mexiletine, the combined treatment with amiodarone and class-I-C drugs such as flecainide and encainide prolongs the cycle length of ventricular tachycardia, but does not suppress induction of ventricular tachycardia during programmed stimulation. Combination therapy with amiodarone and encainide is associated with a remarkable incidence of proarrhythmic effects. Nevertheless, a combination of antiarrhythmic drugs improves efficacy of therapy in selected patients. However, a close monitoring is mandatory because of the risk of proarrhythmia.