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Drug Discovery Today Feb 2018Drug repositioning is hot, and much development time and money can be spared if one selects an old drug and explores the efficacy and safety in a new indication.... (Review)
Review
Drug repositioning is hot, and much development time and money can be spared if one selects an old drug and explores the efficacy and safety in a new indication. Phenytoin is studied and repositioned in many disorders after the initial indication epilepsy (from 1937). Its repositioning in depression was put in the spotlight by the Wall Street icon Jack Dreyfus, already in the 1970s. Innovations in the field of phenytoin still appear to be possible for a number of indications such as wound healing, bipolar disorder and aggression, and via a topical formulation for neuropathic pain. We will discuss wound healing and identified a number of critical issues related to its repositioning in this indication.
Topics: Administration, Topical; Bipolar Disorder; Chemistry, Pharmaceutical; Drug Repositioning; Humans; Neuralgia; Phenytoin; Wound Healing
PubMed: 28993152
DOI: 10.1016/j.drudis.2017.09.020 -
CNS & Neurological Disorders Drug... 2023To evaluate the safety and effectiveness of levetiracetam and phenytoin by evaluating the events of seizure termination and recurrence in children. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the safety and effectiveness of levetiracetam and phenytoin by evaluating the events of seizure termination and recurrence in children.
METHODS
We used the internet databases PubMed, Embase, and Google Scholar to conduct a literature search for the appropriate studies. A meta-analysis was performed to calculate the odds ratio using fixed and random-effects models.
RESULTS
We identified 15 studies that were eligible for the meta-analysis. The incidence of seizure termination within 24 h was 76.9% for levetiracetam and 70.5% for phenytoin. Levetiracetam had a higher number of seizure termination events than phenytoin (P = 0.005, I = 66%). The incidence of seizure recurrence within 24 h was 10% for levetiracetam and 15.6% for phenytoin. Phenytoin had a significantly higher number of seizure recurrence events than levetiracetam (P = 0.00007, I = 21%).
CONCLUSION
The efficacy and safety of levetiracetam are superior to that of phenytoin in children with status epilepticus. Large Randomized Controlled Trial studies are needed to confirm the result in children.
Topics: Child; Humans; Phenytoin; Levetiracetam; Anticonvulsants; Status Epilepticus; Seizures
PubMed: 35538830
DOI: 10.2174/1568007X04666220509215121 -
Journal of Pharmaceutical Sciences Dec 2020This review presents my early exploration in the area of prodrugs and specifically prodrugs of the anticonvulsant, phenytoin, also called diphenylhydantoin. My journey... (Review)
Review
This review presents my early exploration in the area of prodrugs and specifically prodrugs of the anticonvulsant, phenytoin, also called diphenylhydantoin. My journey started in graduate school with an introduction to the prodrug concept and continued for much of my career as I remain fascinated by the topic/technique. I have also included some backstories that the reader might find noteworthy. Prodrug intervention is now recognized as one of the better tools for taking a challenging small molecule drug from un-developable to developable.
Topics: Anticonvulsants; Phenytoin; Prodrugs; Solubility
PubMed: 33002466
DOI: 10.1016/j.xphs.2020.09.037 -
Journal of Periodontology Mar 2021The clinical benefits of autogenous soft tissue grafts are countered by donor site morbidity. The aim of this prospective split-mouth clinical trial is to assess...
BACKGROUND
The clinical benefits of autogenous soft tissue grafts are countered by donor site morbidity. The aim of this prospective split-mouth clinical trial is to assess clinical, histological and patient outcomes following topical phenytoin (PHT) treatment of experimental palatal wounds.
METHODS
Systemically healthy adults were recruited. One 6 mm diameter wound (posterior) and one 4 mm diameter wound (anterior), each 1-1.5 mm deep, were created on both sides of the palate. Wounds on one randomly chosen side received 10% phenytoin USP and contralateral wounds received carrier alone. Biopsies were harvested from anterior wounds (Day 1 or Day 5) and were routinely processed for histology. Posterior wounds were left undisturbed to clinically evaluate healing (using photographs and Healing Score Index) on Days 1, 5, 14, and 21. Questionnaires were used to assess patient-centered outcomes. Data analysis was performed using generalized logistic and generalized linear mixed models.
RESULTS
Twenty participants completed all visits. 30% of participants reported more pain on control side than the PHT side at Day 1 (P = 0.014). PHT treated sites were more likely to not exhibit swelling (OR = 9.35; P = 0.009) and to not experience pain on palpation (OR = 6.278; P = 0.007). PHT significantly and time-dependently affected granulation tissue appearance (P = 0.004). Histologically, there were no significant differences between control and PHT, at any time point (P ≥ 0.853).
CONCLUSIONS
The results of the present study, the first one to report on topical PHT as palatal wound treatment, suggest that PHT application on palatal wounds could result in improved healing outcomes.
Topics: Administration, Topical; Adult; Humans; Palate; Phenytoin; Prospective Studies; Wound Healing
PubMed: 32761909
DOI: 10.1002/JPER.20-0340 -
Neurology India 2023Ongoing seizure in the Emergency Department is a medical emergency and its aggressive management is essential. Prompt antiepileptic therapy with early cessation of... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVE
Ongoing seizure in the Emergency Department is a medical emergency and its aggressive management is essential. Prompt antiepileptic therapy with early cessation of seizure would minimize the morbidity and risk of recurrence. To compare time to seizure control with fosphenytoin to phenytoin protocol in the ED.
MATERIALS AND METHODS
We conducted an observational study on patients with active seizure in the Emergency Department comparing phenytoin versus fosphenytoin protocol over one year.
RESULTS
During the study period, we recruited 121 patients in the phenytoin group and 124 patients in the fosphenytoin group. Generalized tonic-clonic seizure (73.5% in phenytoin vs. 68.5% in fosphenytoin arm) was the most common type of seizure in both the arms. The mean time taken for cessation of seizure in the fosphenytoin arm (17.48 ± 49.24) was less than half of that in the phenytoin arm (37.20 ± 58.17) (mean difference: 19.72, P = 0.004, 95% CI: -33.27 to -6.17). There was a significant decrease in recurrence rates of seizure with phenytoin compared to the fosphenytoin arm (17.7% vs. 31.4%: OR: 0.47, P = 0.013; 95% CI: 0.26-0.86). Favorable STESS (≤2) was higher with phenytoin compared to fosphenytoin (60.3% vs. 48.4%). The overall in-hospital mortality rate in both arms was negligible (0.8%).
CONCLUSION
The mean time for cessation of active seizure with fosphenytoin was less than half that of phenytoin. Despite its higher cost and minor adverse effects when compared to phenytoin, benefits seem to outweigh its limitation.
Topics: Humans; Phenytoin; Seizures; Anticonvulsants; Emergency Service, Hospital
PubMed: 37322738
DOI: 10.4103/0028-3886.378665 -
Seizure Oct 2021We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted... (Review)
Review
BACKGROUND
We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted side effects of ASMs with a particular attention to hair loss, hirsutism, acne, and gingival hyperplasia.
METHODS
This systematic review was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE, and Google Scholar from the inception to 25 March, 2021 were systematically searched. These key words (title/abstract) were used: "hair loss" OR "hirsutism" OR "acne" OR "gingival hyperplasia" AND "seizure" OR "epilepsy" OR "anriseizure" OR "antiepileptic". The exclusion criteria included: non-original studies, articles not in English, and animal studies.
RESULTS
The primary search yielded 3938 studies; 127 studies were related to the topic and were included in the current systematic review. The most robust evidence on cosmetic adverse effects of ASMs were related to phenytoin (causing gingival hyperplasia, hirsutism, and acne) and valproate (causing hair loss and hirsutism); however, many other ASMs were also implicated in causing these cosmetic adverse effects.
CONCLUSION
Antiseizure medications may be associated with various cosmetic adverse effects. Phenytoin and valproate are the most notorious ASMs in this regard; but, other ASMs have also been implicated in causing hair loss, hirsutism, acne, and gingival hyperplasia. Physicians should pay more attention to these significant adverse effects that may affect a patient's facial attractiveness, quality of life, and emotional state.
Topics: Animals; Anticonvulsants; Epilepsy; Humans; Phenytoin; Quality of Life; Valproic Acid
PubMed: 34052629
DOI: 10.1016/j.seizure.2021.05.010 -
Neurotherapeutics : the Journal of the... Jul 2021Genetic testing has yielded major advances in our understanding of the causes of epilepsy. Seizures remain resistant to treatment in a significant proportion of cases,... (Review)
Review
Genetic testing has yielded major advances in our understanding of the causes of epilepsy. Seizures remain resistant to treatment in a significant proportion of cases, particularly in severe, childhood-onset epilepsy, the patient population in which an underlying causative genetic variant is most likely to be identified. A genetic diagnosis can be explanatory as to etiology, and, in some cases, might suggest a therapeutic approach; yet, a clear path from genetic diagnosis to treatment remains unclear in most cases. Here, we discuss theoretical considerations behind the attempted use of small molecules for the treatment of genetic epilepsies, which is but one among various approaches currently under development. We explore a few salient examples and consider the future of the small molecule approach for genetic epilepsies. We conclude that significant additional work is required to understand how genetic variation leads to dysfunction of epilepsy-associated protein targets, and how this impacts the function of diverse subtypes of neurons embedded within distributed brain circuits to yield epilepsy and epilepsy-associated comorbidities. A syndrome- or even variant-specific approach may be required to achieve progress. Advances in the field will require improved methods for large-scale target validation, compound identification and optimization, and the development of accurate model systems that reflect the core features of human epilepsy syndromes, as well as novel approaches towards clinical trials of such compounds in small rare disease cohorts.
Topics: Anticonvulsants; Clinical Trials as Topic; Epilepsy; Genetic Testing; Genetic Therapy; Humans; NAV1.6 Voltage-Gated Sodium Channel; Nerve Tissue Proteins; Phenytoin; Potassium Channels, Sodium-Activated; Quinidine; Voltage-Gated Sodium Channel Blockers
PubMed: 34431030
DOI: 10.1007/s13311-021-01110-w -
Cephalalgia : An International Journal... Sep 2022Scant evidence is available on the use of intravenous pain treatment in acute exacerbations of trigeminal neuralgia. The aim of this descriptive study was to evaluate... (Review)
Review
BACKGROUND
Scant evidence is available on the use of intravenous pain treatment in acute exacerbations of trigeminal neuralgia. The aim of this descriptive study was to evaluate the effectiveness and security of intravenous lacosamide and phenytoin in the treatment of acute trigeminal neuralgia pain.
METHODS
We reviewed patients who attended the emergency department of a tertiary hospital between 2012 and 2020 for exacerbations of trigeminal neuralgia pain and were treated with either intravenous phenytoin or lacosamide for the first time. Primary endpoints were pain relief and adverse effects during the hospital stay. A comparative analysis between both treatment groups was performed.
RESULTS
We studied 144 episodes in 121 patients (median age 61 years, 66.1% women). Trigeminal neuralgia etiology was secondary in 9.9%. Pain relief was observed in 77.8% of 63 patients receiving lacosamide infusions, and adverse effects in 1.6%. Pain relief was observed in 72.8% of 81 phenytoin infusions and adverse effects in 12.3%, all mild. No difference was observed in pain relief between groups, but the proportion of adverse effects was significantly different (p = 0.023). Statistically significant differences were also detected in readmissions within six months, time to readmission, and pain relief status at first follow-up visit.
CONCLUSION
Intravenous lacosamide and phenytoin can be effective and safe treatments for acute pain in trigeminal neuralgia. According to our series, lacosamide might be better tolerated than phenytoin and lead to lower readmissions and sustained pain relief.
Topics: Female; Humans; Lacosamide; Male; Middle Aged; Pain; Phenytoin; Retrospective Studies; Treatment Outcome; Trigeminal Neuralgia
PubMed: 35469475
DOI: 10.1177/03331024221092435 -
Journal of Healthcare Engineering 2022Epilepsy is a chronic neurological disorder that is characterized by episodes of seizure.
OBJECTIVES
Epilepsy is a chronic neurological disorder that is characterized by episodes of seizure.
METHODS
In this study, patients with status epilepticus in the Intensive Care Unit of the Department of Neurology of Qujing First People's Hospital were collected and treated with levetiracetam injection, continuous bedside EEG monitoring (cEEG) technology, and quantitative EEG (qEEG) technique. The inhibitory effects of different doses of levetiracetam injection and sodium valproate on abnormal discharge, the improvement of clinical symptoms, the incidence of adverse reactions, and prognosis were monitored, analyzed, and compared.
RESULTS
Compared with the experimental group of sodium valproate, 1000 mg/d levetiracetam group and 1500 mg/d levetiracetam group had a high probability of successful symptom control and a short control time. The patients had a low recurrence rate and a long recurrence time, and the probability of abnormal discharge in EEG was low.
CONCLUSIONS
The recording results showed that levetiracetam could significantly inhibit the abnormal discharge of patients. Compared with sodium valproate, high-dose levetiracetam is a drug with a rapid effect, good effect, and long action time.
Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Phenytoin; Valproic Acid
PubMed: 35422974
DOI: 10.1155/2022/3789516 -
Annals of Clinical and Translational... Dec 2022Anti-seizure medications that block sodium channels are generally considered contraindicated in Dravet syndrome. There is, however, considerable debate about the...
Anti-seizure medications that block sodium channels are generally considered contraindicated in Dravet syndrome. There is, however, considerable debate about the sodium-channel blocker phenytoin, which is often used for status epilepticus, a frequent feature of Dravet syndrome. We describe four patients with Dravet syndrome in whom long-term phenytoin therapy reduced seizure frequency and duration. In two patients, phenytoin produced prolonged periods without status epilepticus for the first time. Attempting to wean phenytoin in all patients after 1 to 20 years of use resulted in seizure exacerbation. Reintroducing phenytoin improved seizure control, suggesting phenytoin is beneficial in some patients with Dravet syndrome.
Topics: Humans; Phenytoin; Epilepsies, Myoclonic; Status Epilepticus; Sodium Channels; Seizures
PubMed: 36314457
DOI: 10.1002/acn3.51684