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Seizure Jun 1995This review summarizes the studies on the cognitive side-effects of two important antiepileptic drugs: phenytoin and carbamazepine. A large literature database was... (Review)
Review
This review summarizes the studies on the cognitive side-effects of two important antiepileptic drugs: phenytoin and carbamazepine. A large literature database was compiled through the DIMDI computer database and the inspection of recent reviews. Only scientific articles published in peer-reviewed journals during the last 25 years were selected. Of the 358 potentially relevant papers on cognitive effects of AEDs, a total of 16 studies have been found that have studied both carbamazepine and phenytoin. After excluding studies with designs that do not permit valid inferences regarding the cognitive effects of AEDs, only five studies remained. The evaluation of these studies reveal that our current knowledge allows us to draw conclusions about the cognitive side-effects of phenytoin and carbamazepine only with great caution. The claim in reviews that 'both drugs have an impact on cognitive function, PHT to a larger degree than CBZ' is simply not supported by valid 'high quality' data. The same is true for the overall conclusion in more recent reviews that 'drug-induced cognitive effects of these AEDs on cognitive function are probably mild or even negligible'. Apparently, the only information that we have is that the differential impact of PHT and CBZ on cognitive function is not extremely different. No conclusive and reconfirmed data are available on the absolute effects of CBZ and PHT (differences between the two drugs and a no-treatment condition). Our review summarizes some recommendations for future studies.
Topics: Carbamazepine; Clinical Trials as Topic; Cognition; Drug Therapy, Combination; Epilepsy; Humans; Neuropsychological Tests; Phenytoin; Risk Factors
PubMed: 7670773
DOI: 10.1016/s1059-1311(95)80088-3 -
Bioorganic & Medicinal Chemistry Oct 2009The voltage-gated sodium channel remains a rich area for the development of novel blockers. In this study we used comparative molecular field analysis (CoMFA), a...
The voltage-gated sodium channel remains a rich area for the development of novel blockers. In this study we used comparative molecular field analysis (CoMFA), a ligand-based design strategy, to generate a 3D model based upon local anesthetics, hydantoins, and alpha-hydroxyphenylamides to elucidate a SAR for their binding site in the neuronal sodium channel. Correlation by partial least squares (PLS) analysis of in vitro sodium channel binding activity (expressed as pIC(50)) and the CoMFA descriptor column generated a final non-cross-validated model with q(2)=0.926 for the training set. The CoMFA steric and electrostatic maps described a binding site predominately hydrophobic in nature. This model was then used to design and predict a series of novel sodium channel blockers that utilized overlapping structural features of phenytoin, hydroxy amides, and the local anesthetic lidocaine. Synthesis and evaluation of these compounds for their ability to inhibit [(3)H]-batrachotoxin revealed that these compounds have potent sodium channel blockade. Furthermore, the CoMFA model was able to accurately predict the binding of these compounds to the neuronal sodium channel. Synthesis and subsequent sodium channel evaluation of compound 37 (predicted IC(50)=7 microM, actual IC(50)=6 microM), established that novel compounds based on overlapping regions of phenytoin and lidocaine are better binders to the sodium channel than phenytoin itself (IC(50)=40 microM).
Topics: Drug Design; Expert Systems; Inhibitory Concentration 50; Lidocaine; Ligands; Models, Molecular; Phenytoin; Sodium Channel Blockers; Structure-Activity Relationship
PubMed: 19346132
DOI: 10.1016/j.bmc.2008.10.031 -
Singapore Medical Journal Nov 2006This report presents a 30-year-old man who developed subacute phenytoin-induced cerebellar ataxia and parkinsonism that resolved after discontinuation of the phenytoin...
This report presents a 30-year-old man who developed subacute phenytoin-induced cerebellar ataxia and parkinsonism that resolved after discontinuation of the phenytoin treatment. Phenytoin was started for seizure prophylaxis in another health institution where he was referred for bilateral intracerebral orbitofrontal haemorrhage due to a head trauma. To our knowledge, there has been only one other case report describing phenytoin-induced parkinsonism, which was also reversible. The issue of the development of parkinsonism due to the phenytoin toxicity in the case of bilateral orbitofrontal lesion is addressed.
Topics: Adult; Anticonvulsants; Cerebellar Ataxia; Humans; Magnetic Resonance Imaging; Male; Parkinsonian Disorders; Phenytoin
PubMed: 17075669
DOI: No ID Found -
Journal of Pharmacy & Pharmaceutical... 2018The U.S. Pharmacopeia defines excipients as substances other than the active pharmaceutic ingredient (API) that are added in a drug delivery system in order to aid in...
PURPOSE
The U.S. Pharmacopeia defines excipients as substances other than the active pharmaceutic ingredient (API) that are added in a drug delivery system in order to aid in the manufacturing process and enhance stability, bioavailability, safety, effectiveness and delivery of the drug. The 1968 phenytoin intoxication outbreak in Brisbane, Australia, is a classic example of an API-excipient interaction. When administered with CaSO4 the absorption of phenytoin was reduced due to an interaction between the API and the excipient. When CaSO4 was replaced by lactose, the amount of drug absorbed was much higher, resulting in the observed intoxication. It was hypothesized that phenytoin was converted to a calcium salt prior to ingestion. The purpose of this study was to mechanistically investigate the interactions between excipients and phenytoin to confirm the hypothesis of the previous reports.
METHODS
Titration experiments with phenytoin and calcium salt were performed. Isothermal micro calorimetry was used to determine incompatibilities between excipients, phenytoin and milk. NMR was used to characterize the compounds. Dissolution tests containing CaSO4, lactose or sorbitol as excipients were also performed. Both Canadian and United States of America commercially available capsules were tested with milk and water.
RESULTS
The calorimeter results indicate that phenytoin sodium interacts with CaSO4 in aqueous media and the dissolution profile of CaSO4 containing capsules showed a reduced dissolution rate. In addition, phenytoin sodium also interacts with lactose through a Maillard reaction that can occur at body temperature. Likewise, commercial Phenytoin sodium products interacted with milk and the products containing lactose showed browning in water.
CONCLUSION
In Canada and the USA, the reference product contains lactose as an excipient in the formulation, whereas the Canadian generic formulations do not contain lactose. Any clinical relevance of these difference has not been determined. A new incompatibility between phenytoin and lactose has been discovered and an incompatibility with calcium was confirmed, which may have implications in regard to excipients and food effects. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Topics: Anticonvulsants; Calcium Sulfate; Calorimetry; Chromatography, High Pressure Liquid; Humans; Lactose; Phenytoin; Solubility
PubMed: 29702046
DOI: 10.18433/jpps29745 -
Molecules (Basel, Switzerland) Dec 2022Ranolazine, an antianginal and antiarrhythmic drug blocking slow inactivating persistent sodium currents, is described as a compound with anticonvulsant potential. Since...
Ranolazine, an antianginal and antiarrhythmic drug blocking slow inactivating persistent sodium currents, is described as a compound with anticonvulsant potential. Since arrhythmia often accompanies seizures, patients suffering from epilepsy are frequently co-treated with antiepileptic and antiarrhythmic drugs. The aim of this study was to evaluate the effect of ranolazine on maximal-electroshock (MES)-induced seizures in mice as well as interactions between ranolazine and classical antiepileptic drugs in this model of epilepsy. Types of pharmacodynamic interactions were established by isobolographic analysis of obtained data. The main findings of the study were that ranolazine behaves like an antiseizure drug in the MES test. Moreover, ranolazine interacted antagonistically with carbamazepine, phenytoin, and phenobarbital in the proportions of 1:3 and 1:1. These interactions occurred pharmacodynamic, since ranolazine did not change the brain levels of antiepileptic drugs measured in the fluorescence polarization immunoassay. Ranolazine and its combinations with carbamazepine, phenytoin, and phenobarbital did not impair motor coordination evaluated in the chimney test. Unfortunately, an attempt to conduct a passive avoidance task (evaluating long-term memory) resulted in ranolazine-induced delayed lethality. In conclusion, ranolazine exhibits clear-cut anticonvulsant properties in the MES test but interacts antagonistically with some antiepileptic drugs. The obtained results need confirmation in clinical studies. The mechanisms of ranolazine-induced toxicity require specific explanation.
Topics: Animals; Mice; Anticonvulsants; Ranolazine; Phenytoin; Drug Interactions; Seizures; Epilepsy; Carbamazepine; Phenobarbital; Brain; Electroshock; Disease Models, Animal; Dose-Response Relationship, Drug; Avoidance Learning
PubMed: 36558088
DOI: 10.3390/molecules27248955 -
Dermatology Online Journal Jul 2004Oral phenytoin is used widely for the treatment of convulsive disorders and about half the patients treated develop gingival overgrowth as a side effect. The apparent... (Review)
Review
Oral phenytoin is used widely for the treatment of convulsive disorders and about half the patients treated develop gingival overgrowth as a side effect. The apparent stimulatory effect has prompted its assessment in wound healing. Studies have shown topical phenytoin to promote healing of decubitus ulcers, venous stasis ulcers, diabetic ulcers, traumatic wounds, burns, and leprosy trophic ulcers. The mechanism of action has been postulated to be multifactorial. The present literature indicates that topical phenytoin deserves further investigation as a wound-healing agent in controlled dose-finding clinical trials.
Topics: Abscess; Administration, Topical; Burns; Collagenases; Connective Tissue; Diabetic Foot; Drug Evaluation; Enzyme Induction; Fibroblasts; Granulation Tissue; Humans; Keratinocytes; Phenytoin; Powders; Skin Ulcer; Wound Healing; Wounds, Penetrating
PubMed: 15347487
DOI: No ID Found -
The Turkish Journal of Pediatrics 2023This study evaluated the efficacy of a single dose of phenytoin/fosphenytoin (PHT) to control repetitive seizures in children with benign convulsions with mild...
BACKGROUND
This study evaluated the efficacy of a single dose of phenytoin/fosphenytoin (PHT) to control repetitive seizures in children with benign convulsions with mild gastroenteritis (CwG).
METHODS
Children aged between 3 months and 5 years with CwG were retrospectively enrolled. Convulsions with mild gastroenteritis were defined as (a) seizures with acute gastroenteritis without fever or dehydration; (b) normal blood laboratory results; and (c) normal electroencephalography and brain imaging findings. Patients were divided into two groups according to whether or not intravenous PHT (10 mg/kg of phenytoin or phenytoin equivalents) was administered. Clinical manifestations and treatment efficacy were evaluated and compared.
RESULTS
Ten of 41 children eligible for inclusion received PHT. Compared to children in the non-PHT group, those in the PHT group had a higher number of seizures (5.2 ± 2.3 vs. 1.6 ± 1.0, P < 0.001) and a lower serum sodium level (133.5 ± 3.2 mmol/L vs. 137.2 ± 2.6 mmol/L, P = 0.001). Initial serum sodium levels were negatively correlated with seizure frequency (r = -0.438, P = 0.004). In all patients, seizures were completely resolved with a single dose of PHT. There were no significant adverse effects from PHT.
CONCLUSIONS
A single dose of PHT can effectively treat CwG with repetitive seizures. The serum sodium channel may play a role in seizure severity.
Topics: Child; Humans; Infant; Phenytoin; Retrospective Studies; Seizures; Gastroenteritis; Sodium
PubMed: 36866990
DOI: 10.24953/turkjped.2021.4574 -
Pharmacogenetics and Genomics Jun 2012
Review
Topics: Biological Transport; Genetic Variation; Humans; Metabolic Networks and Pathways; Pharmacogenetics; Phenytoin
PubMed: 22569204
DOI: 10.1097/FPC.0b013e32834aeedb -
Therapeutic Drug Monitoring Apr 2023To understand the status of therapeutic drug monitoring (TDM) in China Mainland, and thus lay down the foundation for further improvement in TDM.
OBJECTIVE
To understand the status of therapeutic drug monitoring (TDM) in China Mainland, and thus lay down the foundation for further improvement in TDM.
METHODS
In the present study, a nationwide questionnaire survey was conducted, which was distributed and collected using a mobile-based application. Clinicians, pharmacists, and clinical laboratory physicians belonging to different levels of public hospitals were involved as subjects/objects. The contents of the survey included TDM implementation in their hospital and information regarding their opinions and suggestions on TDM work. Mann-Whitney test was used to compare the difference between top tertiary hospitals and non-top tertiary hospitals.
RESULTS
A total of 475 questionnaires were collected, 383 from top tertiary hospitals (3A hospitals) and 92 from non-top tertiary hospitals (other than 3A hospitals). A total of 240 clinicians, TDM pharmacists, and clinical laboratory physicians were involved, with an effective rate of 50.5%. Top tertiary hospitals were associated with certain advantages, such as the number of TDM testing facilities, annual sample size, number of monitoring varieties, and interpretation rate of monitoring reports, compared with non-top tertiary hospitals. In particular, β-lactamase inhibitor, olanzapine, carbamazepine, and glucocorticoids seemed to be the main projects that clinicians wanted to assess. The drugs for which TDM was commonly performed included vancomycin, valproic acid, carbamazepine, phenytoin sodium, and methotrexate. The most commonly used detection methods include high-performance liquid chromatography, immunization, 2D-LC, and LC-MS. The monitoring concentration range was found to be inconsistent for most of the drugs. Currently, no unified regulation exists for TDM charges in China, which is no more than ¥200 in general. Clinicians rely on pharmacists for professional guidance. Importantly, improvement in the interpretation of monitoring reports, proficiency testing, and cooperation with clinical departments may aid in improving the level of TDM service.
CONCLUSIONS
This survey objectively reflected the current status of TDM work in hospitals in China, and provided a strong reference base for devising strategies for improvement and effective execution of TDM work.
Topics: Humans; Drug Monitoring; Phenytoin; Surveys and Questionnaires; Carbamazepine; China; Benzodiazepines
PubMed: 36920501
DOI: 10.1097/FTD.0000000000001060 -
Acta Bio-medica : Atenei Parmensis Apr 2017Phenytoin is normally used in epilepsy treatment. One of the side effect affecting a significative part of the treated patients is the gingival overgrowth. It could... (Randomized Controlled Trial)
Randomized Controlled Trial
Phenytoin is normally used in epilepsy treatment. One of the side effect affecting a significative part of the treated patients is the gingival overgrowth. It could surely be a correlation between this stimulatory effect and the assessment of phenytoin in wound healing. In fact, some studies of the literature have shown that topical phenytoin promotes healing of traumatic wounds, burns and ulcers by decubitus or stasis (diabetic or venous) and we emphasize, in vitiligo, a particular attention into repigmentation. The related mechanism of action seems to be multifactorial. In the present paper topical phenytoin has been used as wound-healing agent in 19 documented cases of bedsores, divided in treated and placebo group. The used concentration of phenytoin was 5 mg/L dissolved in a water solution of 9 g NaCl /L (0.9% P/V of NaCl). Patches soaked with phenytoin solution were applied over the bedsores along 3 hours every 12 hours. Results showed that phenytoin treated patients healed their wounds significantly before (p<0.001) with respect to controls.
Topics: Administration, Topical; Aged; Aged, 80 and over; Dermatologic Agents; Female; Humans; Male; Middle Aged; Phenytoin; Pressure Ulcer; Transdermal Patch; Wound Healing
PubMed: 28467333
DOI: 10.23750/abm.v88i1.5794