Prevalence of Gingival Hyperplasia Induced by Anticonvulsants: A Systematic Review / Prevalência da Hiperplasia Gengival Induzida pelo uso de anticonvulsivantes: Revisão sistemática

Objective: Gingival hyperplasia (GH) is one of the side effects of anticonvulsant drugs. The aim of this study was to verify the prevalence of GH associated with the use of anticonvulsant, through a systematic review. Material and Methods: Systematic search was done at databases Pubmed and Embase between January 1984 and March of 2020 for identification of articles addressing the prevalence of GH associated with the use of anticonvulsant drugs. The methodological index for non-randomized studies (MINORS) was independently assessed for quality in the selected papers. Results: The search identified 4.471 references. Nine articles were selected and evaluated 632 participants. All of the studies included in the systematic review showed a low risk of bias. The anticonvulsants used by patients were carbamazepine, ethosuximide, phenytoin, primidone, phenobarbital, sodium valproate. The studies showed a correlation between different types of anticonvulsants and GH prevalence, with a range from 0% to 73%. Among the anticonvulsants used, phenytoin showed the greatest incidence of GH, varying between 15.61% and 73% in patients. Conclusion: In the analysis of the results obtained in the literature, it is possible to notice that the great majority of studies presented incidence of GH associated with anticonvulsant use. However, further studies are necessary to understand the anticonvulsant action mechanism inducing GH, as well as the prevention forms, given that GH is a significant side effect. (AU)

Objetivo: Hiperplasia gengival (HG) é um dos efeitos colaterais das drogas anticonvulsivantes. O objetivo deste estudo foi verificar a prevalência de HG associada ao uso de anticonvulsivantes, por meio de uma revisão sistemática. Material e Métodos: A busca sistemática foi realizada nas bases de dados Pubmed e Embase entre janeiro de 1984 e março de 2020 para identificação de artigos que abordassem a prevalência de HG associada ao uso de drogas anticonvulsivantes. Foi avaliado independentemente, o risco de viés através do "Methodological index for non-randomized studies" (MINORS), para análise da qualidade dos trabalhos selecionados. Resultados: A pesquisa identificou 4.471 referências. Nove artigos foram selecionados e avaliaram 632 participantes. Todos os estudos incluídos na revisão sistemática mostraram baixo risco de viés. Os anticonvulsivantes utilizados pelos pacientes foram carbamazepina, etossuximida, fenitoína, primidona, fenobarbital e valproato de sódio. Os estudos mostraram correlação entre os diferentes tipos de anticonvulsivantes e a prevalência de HG, com variação entre 0% a 73%. Entre os anticonvulsivantes utilizados, a fenitoína apresentou a maior incidência de HG, variando entre 15,61% e 73% em pacientes. Conclusão: Na análise dos resultados obtidos na literatura, é possível notar que a grande maioria dos estudos apresentou incidência de HG associada ao uso de anticonvulsivantes. No entanto, estudos adicionais são necessários para compreender o mecanismo de ação do anticonvulsivante para a indução da HG, bem como as formas de prevenção, dado que a HG é um efeito colateral significativo (AU)

Thyroid function in epileptic children who receive carbamazepine, primidone, phenobarbital and valproic acid

In this study, we investigated the changes of the serum levels of thyroidhormones including Thyroxine [T4], Triiodothyronine [T3], T3 resin uptake andThyroid stimulating hormone [TSH] in epileptic children during treatment withanti-epileptic drugs [AEDs] including carbamazepine [CBZ], primidone [PRM],phenobarbital and valproic acid [VPA]. This study consisted of four case-series comparisons, was conducted on 115epileptic children [37 girls and 78 boys with an age range between 2 months and 15 years, mean: 62.06 A +/- 44.97 months]. These children were divided into4 groups who took either phenobarbital [n=29], PRM [n=28], CBZ [n=29], or VPA [n=29] for 3 months. Thyroid hormone levels [T3, T3 resin uptake, T4 and TSH] were measured at the beginning and three months after starting the study. At first, all patients were euthyroid and there were no clinical or laboratory findings suggestive of hypothyroidism. Regarding thyroid hormones before and after the administration of phenobarbital, carbamazepine, valproic acid and primidone, there were no significant changes in serum T3, T4, T3 resin uptake and TSH levels. Our findings showed that short term therapy with phenobarbital, carbamazepine, valproic acid and primidone had no effect on thyroid function tests

Annual Report on External Quality Assessment in Therapeutic Drug Monitoring and Drug of Abuse in Korea (2009) / 임상검사와정도관리

We performed two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Laboratory (KAQACL) in 2009. The number of participating laboratories were 110, which is similar with that of previous 3 years. Average response rates were 97.8% in both trials, similar to those of previous years. Two kinds of control materials were requested to be tested in each trial so that each institution could find the possible systematic errors. The average drug item responded was 6.2 per institution, which was decreased slightly from 6.5 in recent 5 years. The most common test items were valproic acid, digoxin, carbamazepine, phenytoin, and theophylline which were peformed in more than 63.8% of participating laboratories, followed by phenobarbital, cyclosporine, tacrolimus, vancomycin, lithium, methotrexate, amikacin, gentamicin, acetaminophen, tobramycin, salicylate, free phenytoin, amitryptyline, ethosuximide, and primidone. The widely used TDM analyzers were Abbott AxSym (26.9%), followed by Abbott TDx/TDxFLx (24.8%), Roche Cobas Integra (15.1%), Siemens Diagnostics Viva-E (5.5%), Roche cobas c501 (5.1%), Siemens Diagnostics Dimension (3.4%), and many other analyzers. The inter-laboratory coefficients of variations showed similar tendency comparing with those of the previous years. The number of participating laboratories for drug of abuse (DOA) tests were 19, which was slightly increased compared to that of the previous year. Average DOA items were 3.8~4.2. We found the good performance of participating laboratories for DOA. In conclusion, the TDM and DOA external quality assessment of 2009 showed similar performance comparing with that of the recent 3 years.

Annual Report on 2008 External Quality Assessment in Therapeutic Drug Monitoring and Drug of Abuse in Korea (2008) / 임상검사와정도관리

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Laboratory (KAQACL) were performed in 2008. The number of participating laboratories were 114, which is similar with that of the previous year. Average response rates were 97.8% in both trials slightly lower than that of the previous year. Two kinds of control materials were requested to be tested in each trial so that each laboratory could know the possible systematic error. The average drug item was 6.3 per laboratory, which was decreased slightly from 6.8 in recent 5 years, and the maximum was 18 items. The most common test items were valproic acid, digoxin, carbamazepine, theophylline, phenytoin, and phenobarbital which were peformed in more than 52.1% of participating laboratories, followed by cyclosporine, vancomycin, tacrolimus, lithium, methotrexate, amikacin, tobramycin, gentamycin, acetaminophen, salicylate, free phenytoin, primidone, and amitryptyline. The widely used TDM analyzers were Abbott TDx/TDxFLx (35.3%), followed by Abbott AxSym (26.5%) and Roche Cobas Integra (17.3%), Abbott IMx (3.3%), and Siemens Viva E (3.0%). The inter-laboratory coefficients of variations showed similar tendency comparing with those of the previous years. The number of participating laboratories for drug of abuse tests were 17, which is similar to that of the previous year. Average drug item were 3.7 for the 1st trial. We found the relatively good performance as we got the correct answers for all laboratories except 2 laboratories. In conclusion, the TDM external quality assessment of 2008 showed grossly similar pattern comparing with that of previous year.

Annual Report on External Quality Assessment in Therapeutic Drug Monitoring and Drug of Abuse in Korea (2007) / 임상검사와정도관리

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Laboratory (KAQACL) were performed in 2007. Number of participating laboratories were increased to 109, by 5.63% increase comparing with the previous year. Response rates reached 98.7% for both trials slightly lower than that of the previous year. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 6.3 per institution, which was decreased slightly from 6.8 in recent 5 years. The most common test items were valproic acid, digoxin, carbamazepine, theophylline, phenytoin, and phenobarbital which were peformed in more than 55% of the participating laboratories, followed by cyclosporine, vancomycin, lithium, tacrolimus, methotrexate, amikacin, gentamicin, salicylate, tobramycin, acetaminophen, primidone, free phenytoin, and amitryptyline. The inter-laboratory coefficients of variations showed simliar tendency comparing with those of the previous years. We started the proficiency test for drug of abuse from 2007 and got the response from 13 and 17 laboratories in the 1st and 2nd trial, respectively. Average drug items were 3.4 for the 2nd trial. We found the relatively good performances as we got the correct answers from all laboratories except 4 for each one mistake. In conclusion, the TDM external quality assessment of 2007 showed grossly similar pattern comparing with those of previous year and drug of abuse proficiency testing showed a relatively good performance.

Annual Report on External Quality Assessment in Therapeutic Drug Monitoring and Drug of Abuse in Korea (2007) / 임상검사와정도관리

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Laboratory (KAQACL) were performed in 2007. Number of participating laboratories were increased to 109, by 5.63% increase comparing with the previous year. Response rates reached 98.7% for both trials slightly lower than that of the previous year. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 6.3 per institution, which was decreased slightly from 6.8 in recent 5 years. The most common test items were valproic acid, digoxin, carbamazepine, theophylline, phenytoin, and phenobarbital which were peformed in more than 55% of the participating laboratories, followed by cyclosporine, vancomycin, lithium, tacrolimus, methotrexate, amikacin, gentamicin, salicylate, tobramycin, acetaminophen, primidone, free phenytoin, and amitryptyline. The inter-laboratory coefficients of variations showed simliar tendency comparing with those of the previous years. We started the proficiency test for drug of abuse from 2007 and got the response from 13 and 17 laboratories in the 1st and 2nd trial, respectively. Average drug items were 3.4 for the 2nd trial. We found the relatively good performances as we got the correct answers from all laboratories except 4 for each one mistake. In conclusion, the TDM external quality assessment of 2007 showed grossly similar pattern comparing with those of previous year and drug of abuse proficiency testing showed a relatively good performance.

Rapid analysis of antiepileptic drugs in human plasma by micellar electrokinetic capillary chromatography / 药学学报

<p><b>AIM</b>To develop a rapid and feasible method based on micellar electrokinetic capillary chromatography (MECC) for the simultaneous determination of antiepileptic drugs (AEDs)--phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ), primidone (PRM) and clonazepam (CZP) in human plasma.</p><p><b>METHODS</b>Several factors that impact the separation of AEDs with MECC were investigated, such as concentration of sodium dodecyl sulfate (SDS), buffer compositions, pH, organic modifier, internal diameter and temperature, and an optimized MECC running condition was obtained the running buffer consisted of 8 mmol x L(-1) phosphate, 3 mmol x L(-1) sodium tetraborate, and 50 mmol x L(-1) sodium dodecylsulfate (SDS) (pH 8.0), containing acetonitrile (ACN) (18%) as organic modifier. Detection at 210 nm, run at 25 kV at 30 degrees C in a untreated fused silica capillary (50/45.5 cm length, 50 microm ID).</p><p><b>RESULTS</b>The reproducibility of both migration time and relative peak area with MECC analysis were appropriate for the intra- and inter-assay coefficients. The evaluated drugs concentration intervals of PRM 1.0-40.0 microg x mL(-1), PB 1.0-60.0 microg x mL(-1), PHT 1.0-40.0 microg x mL(-1), CBZ 1.0-40.0 microg x mL(-1), CZP 0.2-8.0 microg x mL(-1) were linear with correlation coefficients higher than 0.999 1, and coefficients of the variation of the points of the calibration curve lower than 10%. The recoveries of AEDs varied from 80.0% to 100.0%, depending on the drug, with coefficients of the variation lower than 10.0%.</p><p><b>CONCLUSION</b>The MECC technique is showed to be rapid, simple, efficient and low cost when applied to monitoring therapeutic drugs in patient treated with a combination of PHT and other AEDs such as hepatic enzyme-inducing agents.</p>

Annual Report on External Quality Assessment in Therapeutic Drug Monitoring in Korea (2005) / 임상검사와정도관리

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Pathology (KAQACP) were performed in 2005. The number of participating laboratories were increased to 95, by 6.7% comparing with the previous year. Response rates were 100.0% for both trials just like the two previous years. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 6.7 per institution, which was elevated slightly from 6.5 in recent 5 years. The most common test items were digoxin, valproic acid, carbamazepine, theophylline, phenytoin, and phenobarbital which were peformed in more than 65% of participating laboratories, followed by cyclosporine, lithium, vancomycin, tacrolimus, methotrexate, amikacin, gentamycin, tobramycin, salicylate, primidone, acetaminophen, free phenytoin, amitryptyline, and ethosuximide. The most widely used TDM analyzer was Abbott TDx/TDxFLx (41.7%), followed by Abbott AxSym (23.3%), and Roche Cobas Integra (19.2%). The inter-laboratory coefficients of variations were not much improved comparing with previous years. We also determined cyclosporine with reference method using liquid chromatography-tandem mass spectrometry. In conclusion, the TDM external quality assessment of 2005 showed grossly similar pattern comparing with those of previous year with increasing participating laboratories.

Annual Report on External Quality Assessment in Therapeutic Drug Monitoring in Korea (2004) / 임상검사와정도관리

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) Subcommittee of Korean Association of Quality Assurance for Clinical Pathology (KAQACP) were performed in 2004. Number of participating laboratories were increased to 89, by 11.3% increase comparing with the previous year. Response rates were 100.0% for both trials just like the previous year. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 6.8 per institution, which was elevated slightly from 6.5 in recent 5 years. The most common test items were valproic acid, digoxin, phenytoin, carbamazepine, theophylline, and phenobarbital which were peformed in more than 71% of participating laboratories, followed by cyclosporine, lithium, tacrolimus, vancomycin, methotrexate, amikacin, gentamycin, salicylate, tobramycin, acetaminophen, primidone, free phenytoin, and amitryptyline. The most widely used TDM analyzer was Abbott TDx/TDxFLx (41.6%), followed by Roche Cobas Integra (21.3%), and Abbott AxSym (20.2%). The inter-laboratory coefficients of variations were not greatly improved comparing with previous years. We also determined cyclosporine and tacrolimus with reference method using liquid chromatography-tandem mass spectrometry. In conclusion, the TDM external quality assessment of 2004 showed grossly similar pattern comparing with those of previous year, except the 11.3% increase of participating laboratories.

Annual Report on External Quality Assessment in Therapeutic Drug Monitoring in Korea (2003) / 임상검사와정도관리

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Pathology (KAQACP) were performed in 2003. Number of participating laboratories were 80 which is similar to those of the previous year. Response rates were elevated to 100.0% for both trials. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 7.0 per institution, which was elevated slightly from 6.5 in recent 5 years. The most common test items were valproic acid, digoxin, phenytoin, carbamazepine, theophylline, and phenobarbital, which were peformed in more than 75% of participating laboratories, followed by cyclosporine, lithium, methotrexate, tacrolimus, vancomycin, amikacin, gentamycin, salicylate, tobramycin, acetaminophen, primidone, free phenytoin, and amitryptyline. The most widely used TDM analyzer was Abbott TDx/TDxFLx (52%), but its proportion were decreased slightly comparing with the previous years. The interlaboratory coefficients of variations were not greatly improved comparing with previous years. In conclusion, the TDM external quality assessment of 2003 showed grossly similar pattern comparing with those of previous year, except that the response rate was elevated to 100% and two levels of control material were used in each trials.

Annual Report on External Quality Assessment in Therapeutic Drug Monitoring in Korea (2002) / 임상검사와정도관리

Three trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Pathology (KAQACP) were performed in 2002. Participating laboratories were 79 similar to the previous year. Response rates were 96.3% for 1st, 2nd, and third trials. In the first trial, 20 test items among 27 ones were responded from as least from one laboratory as follows: acetaminophen, amikacin, amitriptyline, carbamazepine, cyclosporine, digoxin, free phenytoin, gentamicin, lithium, methotrexate, phenobarbital, phenytoin, primidone, quinidine, salicylate, tacrolimus (FK-506), theophylline, tobramycin, valproic acid and vancomycin. In the second and third trial, the test items were same with those of 1st trial except the exclusion of quinidine. We included tacrolimus with a whole blood control material in addition to cyclosporine from the first trial. The most common test items were valproic acid, digoxin, phenytoin, carbamazepine, theophylline, and phenobarbital which were peformed in more than 77% of participating laboratories. The most widely used TDM analyzer was Abbott TDx/TDxFLx (56%), but its proportion were decreased slightly comparing with the previous years. In conclusion, we added tacrolimus from the year of TDM proficiency testing in 2002 and found grossly similar pattern comparing with those of previous years.

Simultaneous determination of some anticonvulsants in some pharmaceutical preparations and in serum by high-performance liquid chromatography

The separation and determination of some anticonvnlsant drugs were done in some pharmaceutical preparations and in serum by high-performance liquid chromatography reverse phase. The chromatographic condition were: mobile phase Acetonitril - Methanol - 0.06 M Potassium phosphate 25: 15: 60 W/W pH 4.0, column of octadecyle 5 mico [250 mm x 46 mm] Nucleosil with guard column. The extraction method was based on pharmacopia procedures for pharmaceutical preparations, and the technique used solid / liquid [SEP] for serum. This method permits the Simultaneous determination of all these compounds in pharmaceutical forms for different companies and in serum. Our method is simple and sensitive, based on qualitative and quantitative studies, the Coefficient regression was 0.9998 and Coefficient of variation was between 0.46% - l.t7% and the limit of detection was between 0.9%. Consequently our results showed a very good correlation and they were useful for quality control in the drug industries, the poisoning control centers and in medical laboratories

The Significance of Homocysteine in Epileptic Patients / 대한간질학회지

PURPOSE: Hyperhomocysteinemia was observed in epileptic patients receiving anticonvulsants, especially homozygotes for mtehylenetetrahydrofolate reductase (MTHFR) gene 677C->T mutation. Hyperhomocysteinemia induce atherosclerosis, fetal anticonvulsant syndrome, etc. Therefore, we examined any other factors that might affect the level of homocysteine in epileptic patients. METHODS: We investigated the plasma total homocysteine level in 145 patients with epilepsy. And then we analyzed various factors (clinical findings, neuro-image finding, drugs, MTHFR gene, serum folate and vitamin B12 level) affecting the level of homocysteine. RESULTS: Among the various factors, male, present neurological deficits, frequent seizure attacks, MTHFR gene 677 TT genotype, polypharmacy, and conventional drug (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone, benzodiazpines) than new drug (lamotrigine, vigabatrin, topiramate, oxcarbazepine zonisamide) were related with elevated homocysteine levels. CONCLUSION: We recommend monotherapy with new drugs and higher vitamin requirement in the male epileptic patients of MTHFR TT genotype with neurological deficits and frequent seizure attacks.

Five Cases of Primary Writing Tremor

Primary writing tremor is considered to be a task-specific tremor occurring when handwriting. We describe the clinical and electrophysiological features of 5 patients. Two of the patients had a family history of the tremor. Alcohol was effective in reducing the tremor in 3 of the patients. Two patients showed a co-contraction and three alternate contractions between agonist and antagonist muscles. The frequency of the tremors was 5 to 6 Hz. Primidone and propranolol were effective in reducing tremor. Considering the clinical and electrophysiological features, it is suggested that primary writing tremor might be a variant of essential tremor. (J Korean Neurol Assoc 19(1):52~55, 2001