HLA-B 15:13 Positive in an Indonesian Patient with PhenytoinInduced SJS/TEN

@#Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe forms of delayed hypersensitivity reaction with an underlying immunologic mechanism involving the interaction between HLA and drug molecules. A-35-year-old Javanese-Indonesian-male, with a history of seizures, presented with skin peeling, mucosal erosions, and purulent eye discharges. He was clinically diagnosed as overlapping SJS/TEN, and both phenytoin and valproic acid became the suspected drugs. Unfortunately, the seizure relapsed and alternative antiepileptic drugs were urgently needed. HLA typing was then performed, revealing the presence of HLA-B*15:13, which has been proven to be correlated with phenytoin adverse reaction by previous study. Thus, phenytoin was totally discontinued and he only prescribed monotherapy valproic acid. Given the high prevalence and common use of phenytoin in clinical practice, HLA evaluation before phenytoin prescription in Indonesia is important. Further studies are recommended to provide more evidence regarding the role of HLA-B*15:13 in phenytoin-induced severe hypersensitivity reactions in Indonesia.

Phenytoin Induced Gingival Enlargement

Certain anticonvulsants, cyclosporine, and calcium channel blockers like amlodipine have been shown to produce clinically and histologically similar gingival enlargements in certain susceptible patients in response to local factors. These drugs appear to be similar with respect to their pharmacologic mechanism of action at the cellular level. Therefore, it is tempting to speculate that these agents may act similarly on gingival connective tissue and cause a hyperplastic response. This tissue reaction may involve a disturbance of calcium ion influx into specific cell populations with a resulting alteration in collagen metabolism and other host cell response mechanisms. A connection between ion exchange, folate uptake, collagenase activation, and bacterial inflammation may exist. The management involves Phase I therapy followed by surgical intervention. The purpose of these case reports is to highlight certain modifications in existing surgical techniques like gingivectomy, to have better aesthetic and functional outcome.

Uso de membrana de celulosa oxidada post-gingivectomía en hiperplasia gingival inducida por fenitoína / Use of oxidized cellulose regenerated post-gingivectomy on ginigival hyperplasia induced by phenytoin

Introducción: La hiperplasia gingival es una condición benigna caracterizada por el aumento de volumen de la encía. Algunos fármacos, factores genéticos, aparatología y placa dentobacteriana son factores que pueden inducir esta condición. Objetivo: Devolver la anatomía a la encía brindando una mejor estética y permitiendo una óptima higiene oral. Material y métodos: Paciente masculino de 20 años de edad con antecedentes de fenitoína presenta aumento de volumen en la encía. Resultados: Se obtuvieron resultados estéticos y funcionales satisfactorios con el tratamiento quirúrgico y el uso de membrana de celulosa oxidada. Conclusión: En el manejo de la hiperplasia gingival es importante el enfoque no quirúrgico como control de placa dentobacteriana y medidas de higiene del mismo paciente (AU)

Introduction: Gingival hyperplasia is a benign condition characterized for the grown on the gingival volume. Some drugs, genetic, orthodontic and dental plaque are some factors that can induce this condition. Objective: To return the gingival anatomy, providing a better aesthetic allowing also good oral hygiene. Material and methods: A male 20 years of age with medical history of phenytoin display grown on the gingival volume. Results: Aesthetic and functional results were achieved with the surgical treatment and the oxidized cellulose membrane. Conclusion: In the gingival hyperplasia management is important de non-surgical approach, as dental plaque control and oral hygiene of the patient (AU)

Pericardial effusion associated with DRESS syndrome. Case report / Derrame pericárdico asociado con síndrome de DRESS. Reporte de caso

Abstract Introduction: The DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is a rare but serious and potentially lethal occurrence of a set of signs and symptoms associated with the use certain types of drugs. This syndrome is characterized by a heterogeneous clinical manifestation that, in many cases, results in multisystemic involvement. Case presentation: A 24-year-old man from Calarcá, Colombia, visited the emergency department of the local hospital due to a three-day history of unquantified intermittent fever associated with asthenia, adynamia, anorexia, headache, myalgia, odynophagia, and upper abdominal pain. Due to his condition and based on laboratory findings, he was referred to the Clínica Central del Quindío. The patient, 20 days before the initial assessment, had been prescribed a pharmacological treatment with non-steroidal anti-inflammatory drugs and phenytoin due to a severe cranioencephalic trauma; he also presented with generalized skin rash, elevated transaminases, and moderate eosinophilia. Complementary studies reported mild pericardial effusion, so DRESS syndrome was suspected, and corticosteroid therapy was started, achieving the complete remission of the syndrome. Conclusion: Although the DRESS syndrome has a low incidence, it should always be suspected, especially in patients with cardiac and pericardial involvement. In this case, pericardial involvement was evident, demonstrating that individuals with this syndrome may present with rare symptoms that have a serious impact on their health, as they may significantly increase adverse outcomes and mortality risk.

Resumen Introducción. El síndrome de DRESS (Drug Reaction with Eosinophilia and Systemic symptoms) consiste en la ocurrencia, si bien poco frecuente, pero grave y potencialmente mortal, de un conjunto de signos y síntomas asociados al consumo de cierto tipo de medicamentos. Este síndrome se caracteriza por tener una manifestación clínica heterogénea que, en muchos casos, causa compromiso multisistémico. Presentación del caso. Hombre de 24 años de Calarcá, Colombia, que asistió al servicio de urgencias del hospital local por presentar fiebre intermitente no cuantificada durante 3 días, junto con astenia, adinamia, anorexia, cefalea, mialgias, odinofagia y dolor abdominal superior, y que, debido a su condición y resultados de laboratorio, fue remitido a la Clínica Central del Quindío. El paciente, 20 días antes de la valoración inicial, había recibido tratamiento farmacológico con antiinflamatorios no esteroides y fenitoína por traumatismo craneoencefálico severo; además presentó rash cutáneo generalizado, elevación de transaminasas y eosinofilia moderada. En los estudios complementarios se reportó derrame pericárdico leve, por lo que se sospechó síndrome de DRESS y se inició corticoterapia, lográndose así la remisión completa de la enfermedad. Conclusión. Aunque el síndrome de DRESS tiene una baja incidencia, siempre debe sospecharse, en especial en pacientes que presentan compromiso cardiaco y pericárdico. En este caso se destaca la afectación pericárdica, demostrando que en este síndrome se pueden presentar ma -nifestaciones poco frecuentes, pero con un gran impacto en su salud, ya que pueden aumentar considerablemente los desenlaces adversos y la mortalidad en estos pacientes.

Correlation between Breakthrough Seizures and Serum Level of Phenytoin and Valproate in Indian Patients

Objectives: To determine the optimum range of phenytoin (PHT) and valproate (VAP) levels and find out the critical drug levels below which chances of breakthrough seizures increase in North Indian population. Methodology: A cross-sectional, case-controlled, record-based study was conducted in a quaternary care hospital from September 2018–2019. The case group comprised epilepsy patients on monotherapy with PHT/VAP presenting with breakthrough seizures after at least 6 months of seizure control. Noncompliant, overdose, toxicity, no or partial response, any other psychiatric or neurological disorder, adverse effects, and patients taking two or more antiepileptic drugs were excluded. Results: Data of 100 patients in each group were analyzed. Significantly lower mean levels in cases were observed in PHT (5.74 ± 3.68 mg/L vs. 13.75 ± 4.27 mg/L control) and VAP (24.13 ± 27.39 mg/L vs. 76.37 ± 17.71 mg/L control). A negative correlation of drug levels was observed with age and weight in both the groups. The level/dose ratio in controls (0.05 ± 0.03; 0.09 ± 0.06) was significantly (P < 0.0001) higher than cases (0.02 ± 0.01; 0.02 ± 0.03) in PHT and VAP, respectively. Conclusions: This study identifies the critical levels and level/dose ratio at which the risk of breakthrough seizures increases. A wide level/dose ratio was found in controls, more so in the VAP group. A prospective study with larger group size along with genetic studies should be done to evaluate further.

Oral Use of Phenytoin to Reduce Calcification in Bovine Pericardium and Porcine Aortic Leaflets Implants in Rats

Abstract Introduction: This study aims to test the effect of phenytoin as an inhibitor of the process of dystrophic calcification in bovine pericardium and porcine leaflets implanted in the subcutaneous tissue of rats. Methods: Isolated segments of biomaterials were implanted subcutaneously in young rats. The study groups received 500 mg phenytoin per kilogram of diet per day. After 90 days, samples were collected and quantitative calcification assessment by optical microscopy, radiological studies with mammography, and atomic emission spectrometry were performed. Results: Inflammatory reaction was a frequent finding in all groups when analyzed by optical microscopy. The calcium level assessed by atomic absorption spectrophotometry was significantly lower in the study groups using phenytoin compared to the control groups (control bovine pericardium group X=0.254±0.280 µg/mg; study bovine pericardium group X=0.063±0.025 µg/mg; control porcine aortic leaflets group X=0.640±0.226 µg/mg; study porcine aortic leaflets group X=0.056±0.021 µg/mg; P<0.05). Radiologic studies revealed a statistically significant difference between the groups treated with and without phenytoin (not only regarding the bovine pericardium but also the porcine leaflets). Conclusion: The results obtained suggest that phenytoin reduces the calcification process of bovine pericardium segments and porcine aortic leaflets in subdermal implants in rats; also, the incidence of calcification in bovine pericardium grafts was similar to that of porcine aortic leaflets.

Síndrome DRESS asociado a fenitoína: informe de caso / DRESS syndrome associated with phenytoin: case report

El síndrome DRESS es una reacción adversa dermatológica que puede presentarse debido a diversos medicamentos, y constituye uno de los diagnósticos más importantes por encima del síndrome de Stevens-Johnson. Se trata de un caso relacionado con una reacción adversa de muy baja frecuencia, que está documentada en la literatura científica, a varios medicamentos, entre ellos la fenitoína. Por lo mencionado, la publicación de estos casos resulta escasa y limitada. Las principales preocupaciones del paciente relacionadas con su cuadro clínico radicaban en el gran compromiso cutáneo que lo llevó a hospitalización, dolor e incomodidad, por el cual recurrió al manejo tópico generalizado con vaselina. Los hallazgos clínicos relevantes fueron: eosinofilia severa, ulceraciones cutáneas, hepatitis química y fiebre. Con los hallazgos del cuadro clínico y la evaluación de la escala RegiSCAR se hace el diagnóstico de síndrome DRESS inducido por fenitoína. Se suspende la fenitoína, se inicia levetiracetam y se administran corticosteroides y acetaminofén con evolución favorable. (AU)

DRESS syndrome is a dermatological adverse reaction can occur due to various medications, being one of the most important diagnoses above Steven-Johnson syndrome. This is a case related to a very low frequency adverse reaction that is documented in the scientific literature to several medicines among those, the phenytoin. Therefore, the publication of these cases is scarce and limited. The main concerns of the patients related to their clinical picture were due to the great cutaneous compromise that lead to hospitalization, pain and discomfort for which they resorted to generalized topical management with vaseline (petrolatum). Relevant clinical findings were severe eosinophilia, skin ulcerations, chemical hepatitis and fever. With clinical picture findings and evaluation of the RegiSCAR scale, the diagnosis of Phenytoin-induced DRESS syndrome is made. Phenytoin is discontinued, levetiracetam is started and corticosteroids and acetaminophen are administrated with favorable evolution. (AU)

Current status and standardization conception of the testing quality of therapeutic drug monitoring samples / 中华检验医学杂志

Accurate determination of drug concentration in blood samples is a necessary prerequisite for therapeutic drug monitoring (TDM) and the implementation of precise drug treatment, and it is also one of the important tasks of clinical laboratories.TDM plays an important role in clinical treatment in immunosuppressants (cyclosporine A, tacrolimus), psychotropic drugs (valproic acid, carbamazepine) and other drugs that require monitoring of drug concentration. There are many types of methods used for TDM for the detection of drug concentration in blood samples. At present, only a few immuno-assay methods were approved for marketing with detection systems and kits, most methods used for TDM are high performance liquid chromatography or liquid chromatography-tandem mass spectrometry which belong to laboratory developed tests (LDTs). Detection of TDM samples has many problems, such as incomparable testing results and large bias between different testing systems, including the biasbetween both different methods and different laboratories using the same method. There are several reasons:(1) the traceability chain has not been established, (2) the methods have not yet been standardized, (3) the coverage of the EQA plan is insufficient, (4) the awareness of TDM laboratories to participate in the EQA plan is insufficient, (5) TDM standardization is still in its infancy. These problems restrict the clinical application of TDM and the development of related research work. In order to solve these problems, it is necessary to: (1) Establish a reference system to realize the traceability of the test results; (2) While gradually increasing the TDM EQA plan items, the Trueness evaluation plan should be carried out as soon as possible; (3) Standardized TDM sample testing Technology; (4) Strengthen laboratory management and establish a complete quality management system.

Agrandamiento gingival inducido por fenitoínas / Phenytoin induced gingival enlargement

Se entiende por agrandamiento gingival el incremento en masa y volumen del tejido gingival. Se considera una condición benigna de la cavidad oral, por lo general de manejo rutinario, que logra regularse con medidas simples de control del biofilm microbiano. El agrandamiento gingival puede ser producido por diversas condiciones clínicas, hereditarias, deficiente higiene oral o fármacos. La epilepsia afecta a 1% de la población mundial y requiere el uso de fármacos antiepilépticos o anticonvulsivantes para lograr su control, dentro de éstos la fenitoína actúa como un bloqueador selectivo de los canales de sodio sensibles al voltaje y constituye uno de los fármacos más empleados por su capacidad en el control de crisis focales y generalizadas. La fenitoína se ha relacionado con los agrandamientos gingivales como uno de sus efectos adversos, los cuales se incluyen dentro de las enfermedades por fármaco inducidas en la cavidad oral. El objetivo de este artículo es brindar la información necesaria sobre el manejo correcto de pacientes con agrandamiento gingival producido por fenitoínas y a la vez poder conocer las consecuencias de estos fármacos en la cavidad oral (AU)

Gingival enlargement means the increase in mass and volumen of the gingival tissue. It is considered a benign condition of the oral cavity, usually of routine management, wich can be regulated with simple measures of biofilm control. The gingival enlargement can be produced by diverse clinical conditions, hereditary deficient oral higiene or drugs. Epilepsy affects 1% of the world population and requires the use of antiepileptic or anticonvulsant drugs to achieve its control, within these phenytoin acts as selective blocker or voltage ­ sensitive sodium channels and is one of the most used grugs for its ability to control focal and generalized crises. Phenytoin has been linked to gingival enlargement as one of its adverse effects which is included within the drug diseases induced in the oral cavity. The objective of this article is to provide the necessary information on the correct managment of patients with gingival enlargemen produced by phenytoins and at the same time to know the consequences of these drugs in the oral cavity (AU)

Estudio del índice nivel/dosis de la fenitoína en pacientes epilépticos voluntarios de Mérida / Study of the level/dose index of phenytoin in volunteer epileptic patients from Mérida

INTRODUCCIÓN La fenitoína es usada con mucha frecuencia en nuestro medio, por lo que se requiere hacer estudios de monitorización terapéutica, que contribuya a minimizar los efectos adversos y optimizar la terapia farmacológica. En ese contexto, nuestro objetivo ha sido determinar el índice nivel/dosis de la fenitoína en pacientes epilépticos voluntarios de Mérida. MÉTODOS Se realizó un estudio descriptivo, observacional y por reclutamiento consecutivo concurrente, conformado por 30 pacientes voluntarios con diagnóstico de epilepsia. Las muestras de suero se obtuvieron en niveles mínimos de pacientes que estaban en tratamiento con fenitoína durante 1 mes. Los niveles del fármaco se cuantificaron por el método de Inmunoensayo de enzima donante clonada en el equipo Indiko Thermo Scientific. RESULTADOS El índice nivel/dosis fue de 1,4 y 1,6, la concentración plasmática de 4,8mg/l y 8,0mg/l, la capacidad metabólica de 388,4 y 462,9mg/día, respectivamente en mujeres y hombres. Mientras que el nivel de la concentración plasmática en el estado estacionario fue de 6,5mg/l y 5,5mg/l, la dosis de carga máxima de 237,3mg y de 395,6mg, respectivamente en mujeres y hombres con epilepsia de la ciudad de Mérida. CONCLUSIONES Nuestros resultados sugieren que se debe individualizar la dosis en base al índice nivel/dosis de cada paciente, ya que no se puede extrapolar para todos los pacientes con epilepsia, debido a diversos factores como al fenotipo metabólico y al uso de fármacos inductores e inhibidores enzimáticos.

INTRODUCTION Phenytoin is used very frequently in our environment, so it is necessary to do studies of therapeutic monitoring, which helps to minimize adverse drug reaction and optimize pharmacological therapy. In this context, our objective was to determine the level/dose index of phenytoin in volunteer epileptic patients from Mérida. METHODS A descriptive, observational and consecutive concurrent recruitment study was carried out, consisting of 30 volunteer patients with a diagnosis of epilepsy. The serum samples were obtained in minimum levels from patients who were in treatment with phenytoin for 1 month. The levels of the drug were quantified by the method of donor enzyme immunoassay cloned in the Indiko Thermo Scientific equipment. RESULTS The level/dose index was 1,4 and 1,6, the plasma concentration of 4,8mg/l and 8,0mg/l, the metabolic capacity of 388,4 and 462,9mg/day, respectively in women and men. While the level of plasma concentration at steady state was 6,5mg/l and 5,5mg/l, the maximum loading dose of 237,3mg and 395,6mg, respectively in women and men with epilepsy of the city of Mérida. CONCLUSIONS Our results suggest that the dose should be individualized based on the level/dose index of each patient, since it can not be extrapolated for all patients with epilepsy, due to various factors such as the metabolic phenotype and the use of enzyme-inducing drugs and inhibitors.

Design and Synthesis of New Derivatives of (E)-3-(5-((phenylamino)methyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one for their Anticonvulsant Potential

Objective: The objective of the paper was to design and synthesize new derivatives of ((E)-3-(5-((substitutedphenylamino)methyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one and evaluated for their anticonvulsant potential. Materials and Methods: Various synthesis of (E)-3-(5-(substitutedaminomethyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one derivatives has been synthesized by reacting 2-substituted benzoxazin-4-one with (E)-2-(4-Substituedstyryl)-4H-benzo[d] [1,3]oxazin-4-one. All synthesized compounds have been characterized by the infrared, 1HNMR, and mass spectral analysis. Proposed compounds have been evaluated for anticonvulsant potential by subcutaneous pentylenetetrazole and maximal electroshock seizure model and compared with the reference drug phenytoin and carbamazepine. Neurotoxicity study of the synthesized compounds was also performed. Results and Discussion: The anticonvulsant evaluation of synthesized compound QNM-1, QNM-2, QNM-4, QNM-6, QNM-9, QNM-11, QNM-13, and QNM-15 has shown seizure protection at 100 mg/kg dose after 30 min and 4 h, so they have good onset of action as quickly reach brain and have prolonged action reveal that compound metabolized slowly. Whereas compound QNM-7, QNM-8, and QNM-12 were moderate active and reveal that their high concentration is required to cross blood brain barrier. Compounds QNM-3, QNM-5, QNM-10, and QNM-14 were less active. Compounds having chlorine, bromine, fluorine, and nitro in the phenyl moiety have shown good activity when attached to para group but the addition of meta and ortho group of the same may provide least active compounds and in last fluorine compounds have shown comparative less active compounds. Conclusion:The Pharmacological evaluation suggest that eight synthesized compounds have shown promising anticonvulsant potential and bulkier compounds can easily penetrate BBB to exert their effect.

Effects of Phenytoin on 3 Kinds of Cardiovascular Disease-related Factor in Patients with Epilepsy ：A Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate the effects of phenytoin on 3 kinds of cardiovascular disease-related factors （Folic acid ，vitamin B 12 and homocysteine）in epilepsy patients ，and to provide evidence-based reference for clinical treatment of epilepsy. METHODS ：Retrieved from PubMed ，Google scholar ，CJFD，VIP and Wanfang database ，observational studies about using phenytoin （trial group ） versus using no antiepileptics （control group ） on the levels of folic acid ，vitamin B 12 and homocysteine in serum were collected during Jan. 1991-Jan. 2019. After data extraction of included literatures ，quality evaluation with evaluation criteria for cross-sectional study （AHRQ）scale，Rev Man 5.3 and Stata 11 softwares were used for statistical analysis. RESULTS ：A total of 10 studies were included ，involving 745 patients. Meta-analysis showed that the folic acid level of trial group was significantly lower than control group [SMD ＝－0.90，95％CI（－1.18，－0.62），P＜0.001]；the level of homocysteine in trial group was significantly higher than control group [SMD ＝1.22，95％CI（0.73，1.71），P＜0.001]. There was no significant difference in the levels of vitamin B 12 between 2 groups [SMD ＝－ 0.19，95％ CI（－ 0.39，0.02），P＞0.05]. CONCLUSIONS：Phenytoin can reduce the level of folic acid and increase the level of homocysteine in epilepsy patients.

Diverse presentations of phenytoin toxicity-presenile cataract, encephalopathy and peripheral neuropathy: a case series

One of the most commonly used antiepileptic drugs, phenytoin, has a narrow therapeutic index, high plasma protein binding, non-linearpharmacokinetics and inter-individual variability. It can also present with adverse drug reactions due to phenytoin toxicity with diverse presentations mimicking symptoms of other diseases thus causing diagnostic predicament. This case series reports three such cases of uncommon presentation of phenytoin toxicity like presenile cataract, fluctuating encephalopathy with diurnal variation and peripheral neuropathy. Monitoring of serum drug levels in such cases aids in confirming drug toxicity. Adverse drug reaction monitoring helps in early detection and appropriate management of drug related morbidity.

Effect of age and sex on serum phenytoin concentration in epileptic patients: experience from therapeutic drug monitoring

Background: Phenytoin is a widely prescribed anticonvulsant drug. There is a wide interpatient as well as intrapatient variability in serum phenytoin levels despite standard doses. Phenytoin dosing is challenging because the drug exhibits nonlinear kinetics and interacts with a number of drugs. Children metabolize the drug faster as compared to adults. Ageing is also associated with progressive decline in phenytoin clearance. Many CYP450 enzymes show a sex-dependent difference in activity. The objective for this study was to find the effects of sex and ageing on serum phenytoin levels.Methods: The influence of sex and ageing on the serum phenytoin levels was evaluated retrospectively in 96 anonymized epileptic patients who had received phenytoin alone for more than four weeks. These patients were divided into three age groups, up to 18 years (children), 19-60 years (adults) and more than 60 years (elderly).Results: There were 6.25% children, 84.37% adults and 9.37% elderly. The majority (71.87%) of patients were males. Children achieved a mean phenytoin level of 15.71±4.85 µg/ml after a daily dose of 225.00±75.82 mg. Adults attained a mean serum phenytoin level of 16.12±3.90 µg/ml with a mean daily dose of 282.72±69.44 mg. The elderly achieved a mean serum phenytoin level of 15.85±2.19µg/ml after a mean daily dose of 266.67±70.71 mg. As compared to 77.77% females, 84.05% males had phenytoin levels in therapeutic range. 50.00% children, 82.71% adults, and 100.00% elderly had phenytoin levels in therapeutic range. There was a correlation between sex, age and serum phenytoin levels (r = 0.003 to 0.762).Conclusions: There was a correlation between sex, age and serum phenytoin levels in this study. A better understanding of the effects of sex and age on the clinical pharmacology of phenytoin would enhance the quality of prescribing.

Phenytoin toxicity as a forgoer of schizophrenia like psychosis: a case report

This is a case report describing the toxicity of phenytoin overdose. It is very uncommon to find an anti-epileptic drug causing psychosis and till date only a few studies have found such a co-relation. A psychiatric patient was admitted in our department of medicine with the complain of ingestion of 30 tablets of phenytoin. On examination he was found to have auditory and visual hallucinations. He was restless and had an ill sustained concentration. First and foremost, thing was to stop the prescribed phenytoin tablets and sedate the patient with haloperidol and promethazine. Then, he was switched over to Levetiracetam 500 mg i.v. thrice daily, Clobazam 10 mg once daily and Resperidone 3 mg twice daily. On investigation we found serum phenytoin level >40 mg/dl. This was sufficient to support our diagnosis as after stopping the drug his symptoms improved. There have been case reports of epileptic patient presenting with psychosis but usually after 10-15 years, unlike our case. In our case this time period was reduced to 12 hours as there was a triggering factor present. So, if a known epilepsy patient develops psychosis, the drug history should be given a big importance and if required serum phenytoin level should be assessed to come to the diagnosis of “phenytoin induced schizophrenia like psychosis.

Comparative efficacy of IV phenytoin, IV valproate and IV levetiracetam in childhood seizures

Background: Seizures are the most common pediatric neurologic disorder, with 4% to 10% of children suffering at least one seizure in the first 16 years of life objectives to compare efficacy of IV phenytoin, IV valproate, and IV levetiracetam in childhood seizures between 2months to 16 years of age.Methods: This prospective, randomized, study was done on pediatric patients in the age group of 2 months to 16 years who present actively convulsing to the emergency department of pediatrics.Results: At 24 hours seizures were controlled in 44 (88%) patients out of 50 patients in phenytoin group, 39 (78%) out of 50 patients in levetiracetam group and 46 (92%) out of 50 patients in valproate group (p-value 0.115). The relative risk of seizure recurrence for levetiracetam and phenytoin groups when compared to valproate was 2.75 and 1.5, respectively.Conclusions: Present study demonstrates that IV levetiracetam and IV valproate were comparable to IV phenytoin in terms of seizure control in acute setting. All the three are safe and efficacious. Time to regain consciousness was less in valproate group and long-term seizure control too was also better.

Phenytoin induced toxic epidermal necrolysis: a case report

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are severe idiosyncratic reactions characterized by fever and mucocutaneous lesions leading to necrosis and sloughing of the epidermis. The usage of anticonvulsants like carbamazepine, phenytoin, lamotrigine, phenobarbital are associated with high risk for occurrence of TEN. We present a case of toxic epidermal necrolysis in a 30 year old female probably induced by phenytoin. A 30 year old female was admitted to the emergency medicine department of KIMS hospital, Bengaluru. Lesions over the lips and oral cavity, multiple fluid filled blisters were present diffusely all over the body. Patient had a past history of oral cavity lesions with injection phenytoin. Patient is a known epileptic of over 12 years and was on treatment. Patient had a seizure attack 3 days back and visited nearby hospital and did not inform the doctor of her allergy to phenytoin. Patient was given inj phenytoin after which she developed oral lesions and also presented with fluid filled bullae all over the body. A diagnosis of toxic epidermal necrolysis was made based on clinical history and Scoreten score and was treated with betadine wash, fluconazole and antibiotics .The lesions improved significantly with the above management and patient recovered enough to be discharged from the hospital after 5 days. Severe and serious reactions such as toxic epidermal necrolysis can be caused by commonly used drugs like phenytoin.

Changes in Cardiorespiratory Parameters during the Management of status Epilepticus in Children: A Prospective Randomized Controlled Study

Introduction: Status epilepticus is a common pediatricneurological emergency. Study aimed to compare changes inhemodynamic parameters during the management of pediatricstatus epilepticus using different first line anticonvulsants.Material and Methods: This prospective, randomized, studywas done on Pediatric patients in the age group of 2 monthsto 16 years who present actively convulsing to the emergencydepartment of pediatrics.Results: The mean time to regain consciousness in phenytoin,levetiracetam and valproate groups was 122.3(± 45.4) minutes,120.8(±42.8) minutes and 75.0(±30.7) minutes (mean±S.D)respectively. There was no significant difference in the threegroups in various vital parameters like heart rate, systolicblood pressure, spo2 and respiratory rate recorded at regularintervals in the acute stage (p value > 0.05).Conclusion: All the three anticonvulsants studied are safeand efficacious, and there is no significant difference inthe cardiorespiratory parameters of three groups, and thetime to regain consciousness was less in valproate group incomparison to other groups

Therapeutic drug monitoring of phenytoin using high performance liquid chromatography in a tertiary care hospital of Kashmir, India

Background: Phenytoin is the most commonly used anti-epileptic drug (AED) in this set up due to cost effectiveness and easy availability. Significant fluctuations in serum phenytoin levels leading to toxicities or treatment failures make it an ideal candidate for therapeutic drug monitoring (TDM).Methods: Patients of age ?18 years who were put on phenytoin were enrolled in this study. Estimation of serum phenytoin levels was done using HPLC. Data was analysed using SPSS version 20.0. Chi square test, Kruskal Wallis test were used to analyse the data.Results: A total of 105 patients enrolled in the study, twenty patients (19%) had normal or therapeutic serum phenytoin levels. Thirty-nine patients (37.2%) had sub therapeutic serum phenytoin levels, while forty-six patients (43.8%) had toxic serum phenytoin levels.Conclusions: The TDM of phenytoin should adopt a multi-disciplinary approach with active involvement of neuro-physicians, pharmacologists, pharmacists and other technical staff for improving the overall management of epilepsy. TDM data will provide the clinicians with greater insight into the factors determining the patient’s response to drug therapy.

Effect of Antiepileptic Drugs on Liver Function Tests and Lipid Profile in Paediatric Age Group in Okhla Industrial Area

Epilepsy is the fourth most common neurological disease and affects people of all ages. There are 150,000 new cases of epilepsy every year.The highest incidence of epilepsy in children coupled with the need of long-term antiepileptic treatment could lead to alterations in haemato-biochemical parameters at an early age. Phenytoin and valproic acid are commonly used antiepileptic drugs in children. This study was aimed to assess the serum lipid profile and liver function tests in children with epilepsy on phenytoin or valproic acid monotherapy for 6 months and their control counterparts. Methods: This case control study recruited children from the pediatric outpatient department of Esic Hospital, Okhla. All consecutive children diagnosed with epilepsy as per International League against Epilepsy definition on phenytoin or valproic acid monotherapy for 6 months were enrolled along with the percentage distribution of type of seizures they were suffering. After baseline clinical and anthropometric evaluation (including body mass index [BMI]), the fasting blood samples were analyzed for serum lipid profile and liver function changes. Results: Total of 133 children were enrolled. There were 42 and 36 patients in phenytoin and valproic acid groups respectively and 55 in normal healthy control group. We observed statistically significant high mean total cholesterol and alkaline phosphatase levels in group receiving phenytoin when compared with valproic acid or control group. Conclusion: The lipid and liver enzyme abnormalities may be observed in children on phenytoin or valproic acid therapy, which warrants careful screening and monitoring as young children have immature detoxification mechanisms and a greater variability in dosing owing to a wider range of body size and weight. New epilepsy research should be integrated in areas i.e. Genomics, neuroimaging, neuropsychology and neuropathology for better understanding of the disease and to improve the global health outcomes.