Phenytoin Research Articles

In-situ microscale spectrophotometric determination of phenytoin by using branched gold nanoparticles.

A rapid method for the sensitive detection of phenytoin (PHT) by branched gold nanoparticles (B-AuNPs) is described. These nanoparticles were synthesized by adding methanol as the reducing agent and poly(ethylene glycol) as the stabilizer at 70°C. The B-AuNPs are red in color with an absorption maximum at 540nm when prepared in situ. However, the color becomes increasingly weaker when PHT is present in increasing concentrations. This method can determine PHT over the 67-670ng·mL-1 concentration range, with detection limit of 21ng·mL-1. The relative standard deviation for five replicate measurements at 68 and 530ng·mL-1 of PHT was 3.2% and 1.2%, respectively. The method was applied to thedetermination of PHT in plasma samples of epileptic patients, and theresults were in agreement with those obtained by a standard official method. Graphical abstract Branched gold nanoparticles (AuNPs) prepared in situ have a red color with an absorption maximum at 540nm. The color becomes increasingly weaker with decreasing the intensity of the characteristic SPR band when PHT is present in increasing concentration. The current assay is capable of determining PHT over the 67-670ng·mL-1 concentration range with a limit of detection of 21ng·mL-1.

An update on HLA alleles as pharmacogenetic markers for antiepileptic drug-induced cutaneous adverse reaction

Epilepsy is a common neurological disorder affecting approximately 50 million people worldwide. Antiepileptic drugs (AEDs) are commonly used to treat the disease depending, mainly on the type of seizure. However, the use of AEDs may also lead to cutaneous adverse drug reactions (cADR) such as toxic epidermal necrolysis (TEN), Stevens–Johnson syndrome (SJS), exfoliative dermatitis (ED) and drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), which are unwanted comorbidities in epilepsy. It was first discovered that the HLA-B*15:02 allele was strongly associated with carbamazepine (CBZ)-induced SJS/TEN among Han Chinese and this led to the discovery of other HLA alleles and cytochrome P450 (CYP) genes that were significantly associated with various AED-induced cADRs across various populations. This mini review is an update on the latest findings of the involvement of various HLA alleles and CYP alleles in cADRs caused by CBZ, phenytoin (PHT), oxcarbazepine (OXC) and lamitrogine (LTG) in different case-control studies around the world. From our review, we found that CBZ- and PHT-induced cADRs were more commonly reported than the other AEDs. Therefore, there were more robust pharmacogenetics studies related to these AEDs. OXC- and LTG-induced cADRs were less commonly reported, and so more studies are needed to validate the reported association of the newer reported HLA alleles with these AEDs. It is also important to take into account the allelic frequency within a given population before drawing conclusions about the use of these alleles as genetic markers to prevent AED-induced cADR. Overall, the current body of research point to a combination of alleles as a better pharmacogenetic marker compared to the use of a single gene as a genetic marker for AED-induced cADR.

Insights into Molecular Interactions of human Wnt5b and Frizzled proteins for their role in teratogenicity.

Wnt-Fzd signalling plays vital role in different physiological pathways including embryonic development and supposed to be probable target of many teratogens. The present study was done to investigate the role of human Wnt5b interaction with different isoforms of human Fzds and also the molecular interactions of their complexes with selected known teratogens [Carbamazepine (CBZ), Retinoic acid (RA), Valproic acid (VPA), Aminopterin (AMP) and Phenytoin (PHY)] using Niclosamide (NLM) as standard. The models of hWnt5b and hFzd isoforms, whose solved crystal structures were unavailable, were generated using homology modeling and hWnt5b was subjected to protein-protein docking studies against different isoforms of hFzd. The macromolecular docking studies of hWnt5b-hFzds complexes revealed that hWnt5b had highest binding affinity with hFzd8 and lowest with hFzd1, respectively. The Cysteine rich domain (CRD) of hFzds docked against hWnt5b into a palm shaped opening or near the largest binding pocket as in hWnt5b-hFzd6. The possible role of Wnt-Fzd interactions in developmental toxicity due to selected teratogens were also investigated using molecular docking studies which showed that Retinoic Acid possessed the maximum binding affinity with binding energy of for hWnt5b-hFzd8 complex while VPA was observed to have lowest binding affinity towards all the studied hWnt5b-hFzd complexes.

SYNTHESIS AND EVALUATION OF SOME NEWER QUINAZOLINONYL SUBSTITUTED BENZOXAZEPINYL / BENZOTHIAZEPINYL INDOLES AS POTENT ANTICONVULSANT AGENTS

new series of 3-[3-amino-2-methyl-6-substituted quinazolin-4(3H)-onyl chalconyl)-2-substituted indoles (3-8), 3-[3-Amino-2-methyl-6- substituted quinazolin-4(3H) -onyl-benzoxazepin/benzo -thiazepin- 2-yl] -2-substituted indoles (9-20) and 3-[3-amino-2-methyl-6-substituted quinazolin-4(3H) -onyl-3- (sub-stituted phenylaminomethylene) -benzoxazepin/benzothizepin-2-yl] -2-substitutedindoles (21-44) were synthesised and evaluated for anticonvulsant activity. All these compounds were screened in vivo, for their anticonvulsant activity and acute toxicity. Coumpund 44 , 3-[3-amino-2-methyl-6-bromoquinazolin- 4(3H)-onyl-3- (chlorophenylaminomethylene)-benzothiazepine-2-yl]-2-chloroindole, was found to be most potent compound of this series , more potent than standard drug phenytoin sodium. The homogeneity of all the compounds have been established by elemental analysis, IR and 1H-NMR spectroscopy.

Anticonvulsant and GABAnergic Activity of Nigella sativa oil in Mice

Several experimental studies have described neuroprotective and antioxidant activity of plant extracts and its oil as Nigella sativa. The existing study was conducted to investigate the anticonvulsant activity of Nigella sativa oil. Fifty five male albino mice were used through three experiments; each experiment was taken 1 week. The experiments were pentylenetetrazole induced convulsion, maximal electric shock induced convulsion and neurotoxicity tests. Mice were treated with Nigella sativa oil 10 ml/kg; using sodium valproate (100 mg/kg) and phenytoin sodium (25 mg/kg) orally as standard drugs. In pentylenetetrazole induced convulsion, onset of seizure and generalized seizures were measured, beside the gamma aminobutyric acid and antioxidant enzymes levels assessments. In maximal electric shock, mice were observed for hind limb tonic convulsion. Nigella sativa oil significantly delayed seizure onset after pentylenetetrazole induced convulsion but had no effect on electric shock induced convulsion. Nigella sativa showed a good antioxidant activity and increased gamma amino butyric acid level in brain and had neuroprotective effects.

The impact of topical phenytoin loaded nanostructured lipid carriers in diabetic foot ulceration

ObjectiveThe aim of this study is to develop, and characterize nanostructured lipid carriers (NLCs) of phenytoin (PHT) in order to improve its entrapment efficiency and sustained release to improve the healing process. MethodsTwenty-seven patients with neuropathic diabetic foot ulceration (DFU) were enrolled in this study. Patients were comparable regarding size, grading of ulcer and control of diabetes with no major deformity. All patients were managed by weekly sharp debridement if indicated and offloaded with cast shoes. They were equally divided into three groups: PHT-NLC-hydrogel (0.5%w/v), phenytoin hydrogel (0.5%w/v) and blank hydrogel groups. Changes in wound area were monitored over 2 months. ResultsBaseline wound area of PHT-NLC, PHT and blank hydrogels were 5.50 ± 3.66, 3.94 ± 1.86 and 5.36 ± 2.14 cm2, respectively. Ulcers treated with PHT-NLC hydrogel showed smaller wound area compared to control groups (ρ < 0.05). The overall reduction in ulcer size were 95.82 ± 2.22% for PHT-NLC-hydrogel in comparison to 47.10 ± 4.23% and –34.91 ± 28.33% for PHT and blank-hydrogel (ρ < 0.001), respectively. ConclusionPHT-NLC hydrogel speeds up the healing process of the DFU without adverse effects when compared to the positive and negative control hydrogels. Moreover, the study can open a window for topical application of NLCs loaded with PHT in the treatment of numerous dermatological disorders that resist conventional treatment. Key messageThe delivery of drug molecules and their localization into the skin is the main purpose of the topical dosage forms. In this manuscript, the impact of topical phenytoin loaded nanostructured lipid carrier in improving wound healing in patients with neuropathic diabetic foot ulceration was investigated. Phenytoin loaded nanostructured lipid carrier dressing was found to be more effective than phenytoin hydrogel at the same concentration in healing of neuropathic diabetic foot ulcer.

Development and validation of a HPLC-MS/MS assay for the determination of lutein concentration in human and rat plasma

The aim of this study was to develop and validate a HPLC-MS/MS assay to determine the lutein concentration in plasma samples of human and SD rats. Organic solvent was used for lutein extraction. The extract was injected into a HPLC-MS/MS system. Reversed phase chromatography was performed on a C18 column in gradient mode. Lutein and internal standard (phenytoin sodium) were identified in atmospheric pressure chemical ionization mode using ion transitions of m/z 567.5&gt;549.4 and 205.2&gt;110.8, respectively. The lutein quantification assay was linear over concentrations ranging from 4 to 500 ng/mL. The lower limit of quantification was 4 ng/mL with satisfactory precision and accuracy. The assay presented acceptable intra and inter-batch precision (RSD%) and accuracy (RE%) &lt;8.16% in SD rat plasma and &lt;12.80% in human plasma. The extraction recovery ranged from 50.94 to 60.90% in SD rat plasma and 68.73% in human plasma. The matrix effect for lutein was acceptable and had minimal influence on the results. The method was then applied to determine the lutein concentrations in human plasma after a single oral dose of 20mg lutein. The method described is rapid, selective, sensitive and reproducible. This method can be used for both pharmacokinetic studies and therapeutic drug monitoring purposes.

Effects of phenytoin on serum levels of homocysteine, vitamin B12, folate in patients with epilepsy: A systematic review and meta-analysis (PRISMA-compliant article).

Background:To determine the influence of phenytoin (PHT) monotherapy on the serum levels of homocysteine (Hcy), folate and vitamin B12 in patients with epilepsy.Methods:Literature retrieval was performed through PubMed, Web of Science, Embase, Cochrane Library, Chinese Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database databases as of the end of March 2018. Pooled weighted mean difference (WMD) and 95% CIs were calculated using a random effect model.Results:A total of ten eligible studies were identified. The result revealed that the serum level of homocysteine in PHT-treated patients with epilepsy was significantly higher than that in control group (WMD = 8.47, 95% CI: 6.74 to 10.20, P < .001). In addition, the serum levels of folate (WMD = −3.51, 95% CI: −4.20 to −2.83, P < .001) and vitamin B12 (WMD = −62.23, 95% CI: −83.27 to −41.19, P < .001) were decreased significantly compared with the control group.Conclusions:Our meta-analysis indicates that PHT monotherapy is associated with the increase in the serum homocysteine levels and decreased levels of folate and vitamin B12, and hyperhomocysteinaemia may contribute to the acceleration of the atherosclerotic process. Therefore, the patients under these medications should be monitored plasma homocysteine.

Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population

PurposeAromatic antiepileptic drugs (AEDs) are frequently implicated in cutaneous adverse drug reactions (cADRs), a few of which are associated with certain human leukocyte antigen (HLA) alleles in some populations. We aimed to find HLA-associations with AED-related cADRs among North Indians. MethodsNorth Indian subjects with cADR due to an AED, and those who were AED-tolerant were recruited as cases and controls, respectively. Genotyping for HLA-A, B and DRB1 were performed. Statistical analysis to compare carrier-rates and allele-frequencies between cases and controls (and healthy population, where necessary), was done for HLA-alleles occurring more than twice in either group. Results120 cases {11 - Lamotrigine (LTG), 14 -Valproic acid (VPA), 8 -Levetiracetam (LEV), 35 -Carbamazepine (CBZ) and 52 - Phenytoin (PHT)}, and 250 controls were recruited. Presence of HLA-A*31:01 and HLA-B*51:01 were found to increase the risk of Maculopapular exanthema (MPE) due to CBZ and PHT (OR = 6.38; 95% CI: 1.46–27.75; OR = 4.60; 95% CI: 1.54–13.72, respectively). Among the severe cADRs, HLA-B*57:01(OR = 11.00 95% CI: 1.41–85.81) and HLA-DRB1*07:01 (OR = 7.25; 95% CI: 1.09–48.18) were noted to be significantly associated with CBZ-induced Stevens Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN); HLA-B *51:01 was associated with drug reaction eosinophilia and systemic symptoms (DRESS) caused by PHT (OR = 6.90; 95% CI: 1.38–34.29). ConclusionsWe found significant associations of some HLA alleles with specific cADRs to CBZ and PHT in North Indians, which may need to be tested before AED-initiation; only screening for HLA-B*15:02 may not help in this population.

Comparative bioavailability study of phenytoin in healthy Nepalese volunteers

Our study aimed to assess and compare the bioavailability of Eptoin 100 mg and Epileptin 100mg tablets in Nepalese healthy volunteers. A randomized, two-treatment cross-over study with two weeks’ wash-out period was conducted in 12 healthy non-smoker and non-alcoholic Nepalese male volunteers over a period of 6 months in the department of Clinical Pharmacology and Therapeutic at B. P. Koirala Institute of Health Sciences, Dharan, Nepal after approval from the Institutional Review Committee. The participants were randomized using sealed envelope system and received a single 100 mg oral tablet of either of the formulations with a two week washout period. Blood samples were collected predose and at regular intervals postdose upto 72 hours. Plasma phenytoin levels were estimated by reverse phase high performance liquid chromatography. The analytical method was validated prior to the start of study. Cmax (Peak Plasma Concentration), Tmax (Time to achieve maximum Plasma Concentration), AUC0-72 (Area under plasma concentration time curve 0 to 72 hours), AUC0-∞ (Area under plasma concentration time curve 0 to ∞) and T½ (Elimination half-life) and Kel (Elimination rate constant) were calculated and 80-120% margin (90% confidence interval) was used to assess bioequivalence. ANOVA test was used to analyze the data at P-value of 0.05. All volunteers completed the study. The log-transformed values of Cmax, Tmax, AUC0-t, and AUC0-∞ of the both formulations were within the specified limits and were bioequivalent according to the regulatory definition of bioequivalence based on the rate and extent of absorption. Both products can be considered equally effective in medical practice.&#x0D; Keywords: Bioavailability, Bioequivalence, healthy volunteer, Nepal, phenytoin sodium.

Quality and In-Use Stability Comparison of Brand and Generics of Extended-Release Phenytoin Sodium Capsules

The objective of the present study was to understand quality of brand and generic products of phenytoin sodium by in vitro methods. Three commercial products were selected for the study, 1 brand and 2 generics (product-A, product-B, and product-C). Products were repacked in pharmacy vials and stored for 12 weeks at 30°C/75% RH to simulate in-use conditions. The products were examined visually and microscopically for morphologic changes, spectroscopic and diffractometric methods for chemical changes, and dissolution, assay, and impurities for performance evaluation. Capsules content of the product-A turned yellowish to dark orange color from initial white powder, which indicated a possible chemical interaction between lactose and the drug in addition to disproportionation. This was supported by pH, microscopic, spectroscopic, and X-ray diffraction data. Product-A failed to meet United States Pharmacopoeia dissolution specification of 75% in 120 min after 2-weeks whereas product-B and product-C failed at 6-weeks of in-use stability conditions exposure. Furthermore, product-A also failed to meet United States pharmacopoeia assay and impurities specifications in 12 weeks in-use period. In summary, this study indicated salt disproportionation, chemical interactions, and phase transformations of drug and excipients in the commercial products of phenytoin sodium, which may affect the clinical performance of the product.

Is drug substitution always a solution? Phenytoin induced gingival enlargement – A case report

Gingival enlargement is the most common side effect which is reported with the administration of the anti-epilepsy drug phenytoin (PHT). It is of vital importance as it greatly affects the esthetics and also interferes with the mastication and oral hygiene practices. It is now well known that the presence of gingival inflammation resulting from poor oral hygiene acts as a major risk factor and leads to worsening the condition. Therefore, the patients taking PHT should be made aware of the possible outcomes and the importance of maintaining oral hygiene and periodontal maintenance therapy. This case report describes a case of PHT-induced gingival enlargement in which surgical intervention was done to correct the gingival enlargement, and in spite of patient not discontinuing the drug (PHT), no recurrence of enlargement was seen even after 1 year.

A Zebrafish Behavior Assay for Assessing Anti-Epileptic Drug Efficacy

The availability of zebrafish larvae model of epileptic seizure provides opportunities to identify novel anticonvulsants for treatment of people with epilepsy. However, the major parameters of Zebrafishbehavior assay for assessing anti-epileptic drug efficacy existed disparity. In this study, we chose the high, medium, slow-speed moved distances and the total distances moved for seizure-like activity quantification in individual wells of a 48-well plate in the dark phase. Results also showed that the high-speed moved distances were given a more reasonable and sensitive dose-response curve than the total distances in zebrafish larvae model exposed to 10 mMpentylenetetrazole (PTZ). Moreover, this seizure-like swimming pattern was alleviated by the addition of either phenytoin (PHT) or valproate sodium (VPA), two commonly prescribed anti-epileptic drugs (AEDs). They exhibited concentration-dependent inhibition of both locomotor activity and PTZ-induced c-fostranscription, confirming their anticonvulsant characteristics. Whereas carbamazepine (CBZ) promoted zebrafish larvae movement by 26% at 30 μM and 116.7% at 100 μM, and sharply suppressed zebrafish larvae motility about 94.8% at 300 μM.C-fos expression significantly decreased at 30 μM and 300 μM CBZ, which was found to oppose various aspects of the PTZ-induced changes in activity. These results indicated that this zebrafish larvae model could be useful for studying drug efficacy, predicting drug targets and aiding our understanding of disease etiology.

Estimation of liver enzymes in patients taking antiepileptic drugs in a tertiary care center: A cross-sectional study

Background: A number of antiepileptic drugs (AEDs) are used in the management of epilepsy. Almost all AEDs undergo hepatic biotransformation. Since drugs contribute a major part in causing liver injury, there is a need for identifying it. This study was designed to estimate the prevalence of liver enzyme elevation among patients treated with AEDs. Aims and Objectives: This study aims to estimate the prevalence of liver enzyme elevation and/or liver dysfunction in patients receiving AEDs. Materials and Methods: This cross-sectional descriptive study was conducted in the Department of Neurology, Tirunelveli Medical College Hospital for a period of 6 months. About 150 patients on AEDs, who met the inclusion and exclusion criteria, participated in the study. Demographic data, disease history, drug history, and history of any adverse drug reactions were recorded. Venous blood sample was collected to analyze complete blood count, serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Results: Among 150 patients, 86 were male and 64 were female. Of these, 109 patients were on monotherapy with carbamazepine, sodium valproate, phenytoin, or phenobarbitone and rest 41 were on combination therapy. Serum AST levels were elevated in four patients treated with sodium valproate, phenytoin, or phenobarbitone as monotherapy, whereas ALT enzyme elevation was observed only in one male patient who was on sodium valproate as monotherapy. Serum alkaline phosphatase (ALP) was elevated in 14 patients and decreased in three patients. Conclusion: The magnitude of elevation in serum AST, ALT, and ALP levels with AEDs was found to be statistically insignificant. As such, there was no liver dysfunction in patients receiving AEDs as monotherapy or polytherapy.

Fabrication and characterization of biocompatible pH responsive halloysite nanotubes grafted with sodium alginate for sustained release of phenytoin sodium

Schematic design of a new method for fabrication of biocompatible pH sensitive halloysite nanocomposites for controlled release of phenytoin sodium.

A Prospective, Randomized, Controlled Study For Efficacy of Phenytoin Sodium Powder, Eusol Solution, Nanocrystalline Silver Gel in Diabetic Foot Ulcer

Background Diabetic foot is one of the most significant and devastating complications of diabetes. Not all foot complications can be prevented, but it is possible to dramatically reduce their incidence through appropriate management and prevention. Various dressings are available that fulfils a number of functions like cosmesis, haemostasis, protection, support and absorption. Objectives To study and compare the efficacy of different topical agents like phenytoin sodium powder, eusol solution, nanocrystalline silver gel in patient with diabetic foot ulcer by recording the mean ulcer size pre-treatment, during the course of treatment (1 week, 2 week, 3 week and 4 week follow up) and post- treatment and mean percentage of the wound size healing after treatment. Material & Method This prospective study was conducted in the Department of General Surgery, Geetanjali Medical College & Hospital, affiliated to Geetanjali University from January 2017 to June 2018. 90 patients with diabetic foot ulcers without any other co-morbid conditions and ulcers belonging to Grade I & II as per Wagner diabetic foot ulcers classification were compared with the efficacy of different topical agents. Results Out of 90 patients, there was a highly significant reduction in the mean ulcer size after 2 week, 3 week and 4 week follow up in nanocrystalline silver gel group (p<0.05) as compared to the phenytoin sodium powder and eusol solution group and the formation of granulation tissue was higher in nanocrystalline silver gel group (90%) as compared to phenytoin sodium powder (80%) and eusol solution (73.33%). Conclusion Dressings done with nanocrystalline silver gel was found to be more efficacious than the other topical agents in patients with diabetic foot ulcers in terms of increased rate of wound healing, greater reduction in the mean ulcer size after treatment, absence of pain, swelling and type of discharge after treatment, greater incidence of formation of granulation tissue and less duration of antibiotic therapy and hospital stay.

Efficacy of Dietary Calcium and Vitamin D Supplementation on Rats with Induced Cerebral Palsy

Cerebral palsy is characterized by motor impairment and can present with global physical and mental dysfunction.The aim of the present study was to investigate the effect of dietary calcium and vitamin D supplementation on rats with induced cerebral palsy. Forty five adult male albino rats weighing 180±5gm were divided into seven groups .The 1st group (n=6) was fed on the basal diet (-ve control). The rest of rats (n=39) were injected with 15μl of ethanol to induce cerebral palsy (CP) and daily ingestion of 20 mg/kg.b.w of sodium phenytoin, 3 rats were sacrified to insure occurrence of (CP) .Other groups were 6 each The 2nd group of rats continues and were fed on basal diet (+ve control). Group 3 was fed on daily basal diet supplemented with vitamin D3 by concentration of 600 IU kg/b.w. Groups 4-5 were fed on basal diet supplemented with 40 mg &120 mg of calcium (level1 and 2) with addition of vitamin D, respectively. Group 6 was fed on basal diet supplemented with level 1 Ca with vitamin D supplementation, while group 7 was fed on basal diet supplemented with level 2 Ca with vitamin D supplementation. At the end of the experimental period (10 weeks), rats were scarified. Hence, serum calcium, and vitamin D3 were determined. Results indicated that ethanol CP rats showed a significant (P <0.05) decrease in serum vit.D and serum calcium compared to the negative control one as well as Bone minerals density. It also indicated that supplemented diet with vitamin D and calcium at the highest level improved BWG% as well as serum vitamin D and calcium, Also these supplementation increased the bone mineral density. We concluded that Vit.D and Ca supplementation had beneficial effects on CP rats. It could be recommended that Vit.D and Ca supplementation are worthy trying on cerebral palsy patients.

Effects of amount of excess solid, the type of stirring and sedimentation time on solubility of sodium phenytoin and lamotrigine

Solubility is the maximum quantity of a drug dissolved in a given volume of solvent at a specific temperature. Several factors affect equilibrium solubility. Therefore, different solubility data have been reported for a solute in a certain solvent and temperature in the literature. These variations in solubility are one of the possible reasons for unsuccessful attempts of medicinal chemists for developing models as well as deviation of experimental works for solubility prediction in aqueous, non-aqueous and solvent mixtures. The present research aim is to investigate the effect of the amount of excess solid and the type of stirring on the solubility of drugs. The solubility of two antiepileptic drugs, namely sodium phenytoin and lamotrigine was determined in water, ethanol, and HCl 0.1 M at 37 °C. Different excess amounts of drugs were added to the constant volume of solvent. Additionally, different stirring methods such as magnetic stirrer and shake-flask and sedimentation time were investigated on the solubility values. Saturation solubility of drugs after dilution with water was measured using a spectrophotometer, and the concentration was calculated according to the calibration curve. Amount of excess solid, especially when the drug is in ionized form, and sedimentation time after 24 h have a significant effect on solubility values.

Short-term response to phenytoin sodium in Andersen-Tawil syndrome-1 with a cardiac-dominant phenotype.

Andersen-Tawil syndrome (ATS) is a rare familial periodic paralysis that typically also affects the heart and skeletal system. Ventricular arrhythmias (VAs) are profound and difficult to control, but minimally symptomatic. In this report, we describe an atypical phenotype of ATS in two related families. We also report our experience with phenytoin sodium for the control of resistant VAs in these patients. Between 2014 and 2018, seven siblings were diagnosed with ATS on the basis of cardiac arrhythmias and genetic evaluation. Heterozygous mutation with c.431G>C (p.G144A) in exon 2 of KCNJ2 gene was observed in all patients. Characteristic cardiac manifestations were noted in all patients but periodic paralysis or objective neurological involvement was distinctly absent. Phenytoin was considered for control of symptomatic VA in three patients. Intake of oral phenytoin (5mg/kg/day) for 1month completely suppressed VA (<1% in 24-h Holter monitoring) in two patients, and significantly in the third (8% per 24h) patient. Phenytoin was well-tolerated in all three patients. We describe a cardiac-predominant phenotype in ATS. ATS should be suspected in patients with typical cardiac manifestations even in the absence of periodic paralysis. Our initial experience with short-term use of phenytoin for control of resistant VAs is encouraging.

A systematic review of phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets in China.

Objective:In this study, we aimed to review the literature on phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets (CPEHTT).Method:A literature search was performed in the following databases: WANFANG DATA, HowNet, National Library Reference and Consultation Alliance, Full-text Database of Foreign Medical Journals, PubMed and Ovid. The search terms were “Compound Phenytoin Sodium, ephedrine Hydrochloride and Theophylline Tablets,” and “poisoning,” or “toxicity,” in Chinese and in English.Result:Ten articles including 104 patients with CPEHTT intoxication were identified. The ages of the patients ranged from 52 to 82 years. Sixty-seven patients were male and thirty-seven patients were female (the male/female ratio, approximately 2:1). The most common clinical manifestations were dizziness (85%) and ataxia (85%), followed by limb weakness (65%), diplopia (25%), binocular horizontal nystagmus (24%), limb numbness (13%), nausea and vomiting (12%), somnolence (10%), tremor and high muscle tension (7%), lag in response (5%), dysarthria (6%), choking cough (2%), auditory hallucination and visual fantasy (1%), and involuntary movement (1%). All patients had chronic lung disease, and the most common disease was chronic bronchitis. The dosage ranged 4 to 15 tablets per day with medication duration of more than 1 year for most patients.Conclusion:The CPEHTT intoxication caused by phenytoin toxicity represents a drug safety problem in China. The common clinical manifestations, serum phenytoin concentrations, and associated factors of CPEHTT intoxication are important for diagnosis and prevention. These findings may help guide clinicians to correctly attend to the use of CPEHTT and avoid its toxicity.