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Cleveland Clinic Journal of Medicine Sep 2022
Topics: Humans; Phenytoin; Gingival Overgrowth; Anticonvulsants
PubMed: 37907437
DOI: 10.3949/ccjm.89a.21107 -
Indian Journal of Pharmacology 2019Phenytoin is an anticonvulsant which is also a Class IB antiarrhythmic. Its common adverse drug reactions (ADRs) include gastrointestinal symptoms, psychiatric...
Phenytoin is an anticonvulsant which is also a Class IB antiarrhythmic. Its common adverse drug reactions (ADRs) include gastrointestinal symptoms, psychiatric disorders, gingival hyperplasia, and rash. Bradycardia and hypotension following intravenous (IV) phenytoin are rare ADRs. We report the case of a 62-year-old female with subarachnoid hemorrhage and right bundle branch block, who developed sinus bradycardia and hypotension on administration of IV phenytoin. This case report serves as a note for caution on patient selection for the administration of phenytoin and highlights the need for specific guidelines on the same.
Topics: Anticonvulsants; Bradycardia; Female; Humans; Hypotension; Middle Aged; Phenytoin
PubMed: 31142948
DOI: 10.4103/ijp.IJP_254_17 -
Epilepsia Sep 2016Fracture risk is a serious comorbidity in epilepsy and may relate to the use of antiepileptic drugs (AEDs). Many AEDs inhibit ion channel function, and the expression of...
OBJECTIVE
Fracture risk is a serious comorbidity in epilepsy and may relate to the use of antiepileptic drugs (AEDs). Many AEDs inhibit ion channel function, and the expression of these channels in osteoblasts raises the question of whether altered bone signaling increases bone fragility. We aimed to confirm the expression of voltage-gated sodium (NaV ) channels in mouse osteoblasts, and to investigate the action of carbamazepine and phenytoin on NaV channels.
METHODS
Immunocytochemistry was performed on primary calvarial osteoblasts extracted from neonatal C57BL/6J mice and additional RNA sequencing (RNASeq) was included to confirm expression of NaV . Whole-cell patch-clamp recordings were made to identify the native currents expressed and to assess the actions of carbamazepine (50 μm) or phenytoin (50 μm).
RESULTS
NaV expression was demonstrated with immunocytochemistry, RNA sequencing, and functionally, with demonstration of robust tetrodotoxin-sensitive and voltage-activated inward currents. Application of carbamazepine or phenytoin resulted in significant inhibition of current amplitude for carbamazepine (31.6 ± 5.9%, n = 9; p < 0.001), and for phenytoin (35.5 ± 6.9%, n = 7; p < 0.001).
SIGNIFICANCE
Mouse osteoblasts express NaV , and native NaV currents are blocked by carbamazepine and phenytoin, supporting our hypothesis that AEDs can directly influence osteoblast function and potentially affect bone strength.
Topics: Animals; Animals, Newborn; Anticonvulsants; Carbamazepine; Cells, Cultured; Dose-Response Relationship, Drug; Electric Stimulation; Gene Expression Regulation; Membrane Potentials; Mice; Mice, Inbred C57BL; Osteoblasts; Patch-Clamp Techniques; Phenytoin; RNA, Messenger; Sodium Channel Blockers; Sodium Channels; Tetrodotoxin
PubMed: 27440235
DOI: 10.1111/epi.13474 -
BMJ Clinical Evidence Mar 2009Trigeminal neuralgia is a sudden, unilateral, brief, stabbing, recurrent pain in the distribution of one or more branches of the fifth cranial nerve. Pain occurs in... (Review)
Review
INTRODUCTION
Trigeminal neuralgia is a sudden, unilateral, brief, stabbing, recurrent pain in the distribution of one or more branches of the fifth cranial nerve. Pain occurs in paroxysms which last from a few seconds to 2 minutes. The frequency of the paroxysms ranges from a few to hundreds of attacks a day. Periods of remission can last for months to years, but tend to shorten over time.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with trigeminal neuralgia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: ablative neurosurgical techniques to the Gasserian ganglion, baclofen, carbamazepine, clonazepam, cryotherapy of peripheral nerves, gabapentin, lamotrigine, microvascular decompression, nerve block, oxcarbazepine, peripheral acupuncture, phenytoin, proparacaine eye drops, sodium valproate, stereotactic radiosurgery, tizanidine, and topiramate.
Topics: Humans; Ophthalmic Solutions; Pain; Pain Measurement; Phenytoin; Radiosurgery; Trigeminal Ganglion; Trigeminal Neuralgia
PubMed: 19445753
DOI: No ID Found -
Bioanalysis Feb 2022The purpose of the study was to find methods suitable for measuring the free concentrations of testosterone and phenytoin. Sample solutions of the compounds in buffer...
The purpose of the study was to find methods suitable for measuring the free concentrations of testosterone and phenytoin. Sample solutions of the compounds in buffer and human albumin were processed using liquid-liquid extraction, microextraction and ultrafiltration and analyzed by LC-MS/MS. Liquid-liquid extraction with dibutyl phthalate provided complete extraction from buffer solutions and partial extraction from albumin samples. Spintip C18 devices provided exhaustive extraction from buffer and albumin samples. Spintip C8 devices offered complete extraction from buffer and approximately 50% recovery from albumin samples. Centrifree ultrafiltration devices showed high recovery of free concentrations from all the samples, while Amicon and Nanosep devices provided partial recovery. Spintip C8 and Centrifree devices proved useful for measuring free concentrations.
Topics: Humans; Liquid Phase Microextraction; Liquid-Liquid Extraction; Phenytoin; Testosterone; Ultrafiltration
PubMed: 35034505
DOI: 10.4155/bio-2021-0249 -
Neurology India 2021
Topics: Anticonvulsants; Epilepsy; Humans; Phenytoin
PubMed: 34507421
DOI: 10.4103/0028-3886.325320 -
IARC Monographs on the Evaluation of... 1996
Review
Topics: Animals; Anticonvulsants; Carcinogenicity Tests; Carcinogens; Humans; Phenytoin
PubMed: 9097125
DOI: No ID Found -
Molecular Cancer Jan 2015Voltage-gated Na(+) channels (VGSCs) are heteromeric protein complexes containing pore-forming α subunits and smaller, non-pore-forming β subunits. VGSCs are...
BACKGROUND
Voltage-gated Na(+) channels (VGSCs) are heteromeric protein complexes containing pore-forming α subunits and smaller, non-pore-forming β subunits. VGSCs are classically expressed in electrically excitable cells, e.g. neurons. VGSCs are also expressed in tumour cells, including breast cancer (BCa) cells, where they enhance cellular migration and invasion. However, despite extensive work defining in detail the molecular mechanisms underlying the expression of VGSCs and their pro-invasive role in cancer cells, there has been a notable lack of clinically relevant in vivo data exploring their value as potential therapeutic targets.
FINDINGS
We have previously reported that the VGSC-blocking antiepileptic drug phenytoin inhibits the migration and invasion of metastatic MDA-MB-231 cells in vitro. The purpose of the present study was to establish whether VGSCs might be viable therapeutic targets by testing the effect of phenytoin on tumour growth and metastasis in vivo. We found that expression of Nav1.5, previously detected in MDA-MB-231 cells in vitro, was retained on cells in orthotopic xenografts. Treatment with phenytoin, at a dose equivalent to that used to treat epilepsy (60 mg/kg; daily), significantly reduced tumour growth, without affecting animal weight. Phenytoin also reduced cancer cell proliferation in vivo and invasion into surrounding mammary tissue. Finally, phenytoin significantly reduced metastasis to the liver, lungs and spleen.
CONCLUSIONS
This is the first study showing that phenytoin reduces breast tumour growth and metastasis in vivo. We propose that pharmacologically targeting VGSCs, by repurposing antiepileptic or antiarrhythmic drugs, should be further studied as a potentially novel anti-cancer therapy.
Topics: Animals; Anticonvulsants; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Female; Humans; Mice; Neoplasm Metastasis; Neovascularization, Pathologic; Phenytoin; Sodium Channel Blockers; Sodium Channels; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 25623198
DOI: 10.1186/s12943-014-0277-x -
Canadian Medical Association Journal Jun 1963The main clinical types of epilepsy and their treatment are described. The treatment of choice in petit mal epilepsy is trimethadione (Trimedone) 0.3 g., three to six...
The main clinical types of epilepsy and their treatment are described. The treatment of choice in petit mal epilepsy is trimethadione (Trimedone) 0.3 g., three to six times a day, or acetazolamide (Diamox) 125-250 mg., three to four times a day. Phenobarbital is usually given as well to prevent grand mal seizures. Diphenylhydantoin sodium (Dilantin Sodium), 100 mg., and/or phenobarbital, 30-100 mg., three to four times a day, is recommended in patients with focal and grand mal epilepsy. Psychomotor automatisms are a form of focal seizure. Primidone (Mysoline), in doses of 125-250 mg. two to three times a day, is a very useful anticonvulsant in patients with myoclonic features, psychomotor automatisms and grand mal seizures. Primidone should be started in small doses. Drug reactions, especially cerebellar ataxia in the case of diphenylhydantoin and blood dyscrasias in the case of some drugs, should be recognized. Excessive drowsiness can be avoided by proper dosage and proper timing of drug administration. Patients should be seen regularly at least two to three times a year. The objective of treatment is to achieve optimum control of seizures by using the appropriate drug in adequate dosage. Social adaptation is good in the majority of patients, who should be encouraged to carry on their life independently, usually free to marry and have children. Attention to special occupational hazards has to be considered. Education of employers and employees is often necessary. Special work arrangements are occasionally indicated for selected patients. Patients should be seizure-free for two to three years before permission is given to drive an automobile.
Topics: Acetazolamide; Anticonvulsants; Automatism; Child; Epilepsy; Epilepsy, Absence; Epilepsy, Tonic-Clonic; Humans; Phenobarbital; Phenytoin; Primidone; Seizures
PubMed: 13969008
DOI: No ID Found -
Yonsei Medical Journal Aug 2009The pharmacokinetics of phenytoin is complicated by genetic and environmental differences. It is, therefore, important to monitor the serum concentrations in patients...
PURPOSE
The pharmacokinetics of phenytoin is complicated by genetic and environmental differences. It is, therefore, important to monitor the serum concentrations in patients who receive phenytoin. Because most of the phenytoin in serum is bound to proteins, the level of serum albumin influences the amount of free phenytoin.
MATERIALS AND METHODS
We compared the measured and calculated free phenytoin levels in epileptic patients who were taking phenytoin monotherapy, using the Sheiner-Tozer equation. A total of 49 patients (30 men and 19 women; age range, 15 - 87 years) were included in the study and their trough serum phenytoin and albumin concentrations were analyzed.
RESULTS
The linear correlation between free and total phenytoin concentrations was moderate (r = 0.822, p < 0.001). The mean difference between measured and calculated free phenytoin was large (0.65 +/- 0.88 microg/mL; 95% confidence interval (CI), -1.11 to 2.41). After dividing the patients into groups by albumin concentration, hypoalbuminemic patients (< 3.5 g/dL) more often had a greater percent difference (> or = 20%) than observed in the normoalbuminemic (> or = 3.5 g/dL) group.
CONCLUSION
In hypoalbuminemic patients, the measurement of free phenytoin level is necessary to properly evaluate the phenytoin level than that calculated from total phenytoin level.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Epilepsy; Female; Humans; Male; Middle Aged; Phenytoin; Young Adult
PubMed: 19718399
DOI: 10.3349/ymj.2009.50.4.517