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Indian Journal of Critical Care... Jun 2022Hegde A. Drug Levels in ICU - T or F. Indian J Crit Care Med 2022;26(6):663.
Hegde A. Drug Levels in ICU - T or F. Indian J Crit Care Med 2022;26(6):663.
PubMed: 35836634
DOI: 10.5005/jp-journals-10071-24261 -
Neuro-oncology Practice Oct 2021Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic... (Review)
Review
BACKGROUND
Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic review, we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma.
METHODS
Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched up to June 2020. Three different outcomes for both mono- and polytherapy were extracted from all eligible articles: (i) seizure freedom; (ii) ≥50% reduction in seizure frequency; and (iii) treatment failure. Weighted averages (WA) were calculated for outcomes at 6 and 12 months.
RESULTS
A total of 66 studies were included. Regarding the individual outcomes on the efficacy of monotherapy, the highest seizure freedom rate at 6 months was with phenytoin (WA = 72%) while at 12-month pregabalin (WA = 75%) and levetiracetam (WA = 74%) showed highest efficacy. Concerning ≥50% seizure reduction rates, levetiracetam showed highest efficacy at 6 and 12 months (WAs of 82% and 97%, respectively). However, treatment failure rates at 12 months were highest for phenytoin (WA = 34%) and pregabalin (41%). When comparing the described polytherapy combinations with follow-up of ≥6 months, levetiracetam combined with phenytoin was most effective followed by levetiracetam combined with valproic acid.
CONCLUSION
Given the heterogeneous patient populations and the low scientific quality across the different studies, seizure rates need to be interpreted with caution. Based on the current limited evidence, with the ranking of AEDs being confined to the AEDs studied, levetiracetam, phenytoin, and pregabalin seem to be most effective as AED monotherapy in glioma patients with epilepsy, with levetiracetam showing the lowest treatment failure rate, compared to the other AEDs studied.
PubMed: 34589231
DOI: 10.1093/nop/npab030 -
Frontiers in Public Health 2022Drug-induced gingival overgrowth (DIGO) is a frequent adverse medication reaction that is generally caused by cyclosporine, phenytoin, and nifedipine, which belong to... (Review)
Review
OBJECTIVES
Drug-induced gingival overgrowth (DIGO) is a frequent adverse medication reaction that is generally caused by cyclosporine, phenytoin, and nifedipine, which belong to the category of immunosuppressants, anticonvulsants, and calcium channel blockers, respectively. This bibliometric analysis aims to depict the main citation characteristics and analyze the research trends in DIGO investigations.
METHODS
An exhaustive search was performed in the Scopus database to create the bibliometric list of DIGO in the syntax. Furthermore, the information related to the number of citations, drugs related to DIGO, study topic and design, authorship, publication year, journal, contributing institution, country of origin, and the department was extracted.
RESULTS
In total, 399 papers on DIGO were retrieved in this study. The total number of citations and that after the removal of self-citations were 7,814 and 7,314, respectively. The mean number of citations was 19.6 in a range of 0-608. The main paper types were articles (76.94%) and reviews (19.55%). A remarkable increasing trend in the number of citations has been observed since 1994. Cyclosporine (44.89%) is the most commonly used drug that shares a close relationship with DIGO, followed by phenytoin (18.22%), nifedipine (17.93%), and amlodipine (6.81%). The review (27.82%) type constituted the most widely used design in the DIGO studies. According to the top 20 keywords, the risk factors and pathogenesis of DIGO have been prominent topics of research works for several years.
CONCLUSIONS
This bibliometric analysis will facilitate the understanding of researchers and clinicians, especially those at the beginning of their careers in periodontology on DIGO, by identifying landmark research and providing an overview of this field.
Topics: Amlodipine; Anticonvulsants; Bibliometrics; Calcium Channel Blockers; Cyclosporine; Gingival Overgrowth; Humans; Immunosuppressive Agents; Nifedipine; Phenytoin
PubMed: 36148356
DOI: 10.3389/fpubh.2022.979861 -
Current Neuropharmacology 2023Antiseizure medications and drugs for psychiatric diseases are frequently used in combination. In this context, pharmacokinetic interactions between these drugs may...
Antiseizure medications and drugs for psychiatric diseases are frequently used in combination. In this context, pharmacokinetic interactions between these drugs may occur. The vast majority of these interactions are primarily observed at a metabolic level and result from changes in the activity of the cytochrome P450 (CYP). Carbamazepine, phenytoin, and barbiturates induce the oxidative biotransformation and can consequently reduce the plasma concentrations of tricyclic antidepressants, many typical and atypical antipsychotics and some benzodiazepines. Newer antiseizure medications show a lower potential for clinically relevant interactions with drugs for psychiatric disease. The pharmacokinetics of many antiseizure medications is not influenced by antipsychotics and anxiolytics, while some newer antidepressants, namely fluoxetine, fluvoxamine and viloxazine, may inhibit CYP enzymes leading to increased serum concentrations of some antiseizure medications, including phenytoin and carbamazepine. Clinically relevant pharmacokinetic interactions may be anticipated by knowledge of CYP enzymes involved in the biotransformation of individual medications and of the influence of the specific comedication on the activity of these CYP enzymes. As a general rule, these interactions can be managed by careful evaluation of clinical response and, when indicated, individualized dosage adjustments guided by measurement of drugs serum concentrations, especially if pharmacokinetic interactions may cause any change in seizure control or signs of toxicity. Further studies are required to improve predictions of pharmacokinetic interactions between antiseizure medications and drugs for psychiatric diseases providing practical helps for clinicians in the clinical setting.
Topics: Humans; Antipsychotic Agents; Phenytoin; Drug Interactions; Antidepressive Agents; Benzodiazepines; Carbamazepine; Cytochrome P-450 Enzyme System
PubMed: 35611779
DOI: 10.2174/1570159X20666220524121645 -
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 -
The Journal of Pediatric Pharmacology... 2020Since its introduction in 1950, phenytoin (PHT) has been the premier parenteral anticonvulsant used in the management of generalized convulsive status epileptics (GCSE)...
Since its introduction in 1950, phenytoin (PHT) has been the premier parenteral anticonvulsant used in the management of generalized convulsive status epileptics (GCSE) that is refractory to benzodiazepines. Without question, its arrival was vital to the care of patients with acute seizures and was a welcomed alternative to paraldehyde and phenobarbital. However, after more than half a century of use, there continues to be insufficient evidence-based data to support its efficacy over other anticonvulsants as a first-line agent in pediatric or adult patients with GCSE. This coupled with its narrow mechanism of action, complex pharmacokinetics and pharmacogenomics, drug-drug interactions, unique adverse effects, and formulation issues that make administration difficult mandates that PHT be replaced by safer and superiorly effective anticonvulsants for the treatment of GCSE when benzodiazepines are ineffective. We believe that levetiracetam should become the preferred agent for seizures unresponsive to or recurring after treatment with a benzodiazepine as it is at least equally effective to PHT and has several important advantages. PHT has overstayed its welcome and it is simply time for it to exit the realm of acute seizure management as a first-line agent for benzodiazepine-refractory GCSE.
PubMed: 31897070
DOI: 10.5863/1551-6776-25.1.4 -
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 -
The Canadian Journal of Hospital... 2022Status epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line... (Review)
Review
BACKGROUND
Status epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line treatment but fails to control SE in about one-third of patients. Levetiracetam may be used for SE that is refractory to benzodiazepine therapy.
OBJECTIVE
To examine, by means of a systematic review, the role of IV levetiracetam for the treatment of SE in adults.
DATA SOURCES
MEDLINE, Embase, CENTRAL, and CINAHL databases were searched, from inception to August 18, 2020.
STUDY SELECTION AND DATA EXTRACTION
Included in this review were prospective randomized controlled trials comparing levetiracetam with another antiepileptic drug, given with or after a benzodiazepine, in adult patients with SE. The primary outcome was cessation of SE. Quality of evidence was assessed with the Cochrane risk-of-bias tool. Characteristics of the included studies were reported using descriptive statistics.
DATA SYNTHESIS
Five studies compared IV levetiracetam with valproic acid, phenytoin (or its prodrug fosphenytoin), or both. All 5 studies found no statistically significant differences in efficacy or safety end points. There were numerically more cases of hypotension and respiratory failure with phenytoin, and more cases of psychiatric adverse effects (e.g., post-ictal psychosis) with levetiracetam.
CONCLUSIONS
Available evidence suggests that levetiracetam is as effective as valproic acid or phenytoin for the cessation of SE in adults. Other factors should therefore dictate the choice of antiepileptic drug for patients with SE, such as adverse effect profile, logistics of administration, drug cost, inclusion on hospital formularies, and drug availability.
PubMed: 34987263
DOI: 10.4212/cjhp.v75i1.3254 -
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 -
Current Neuropharmacology 2021Exposure in the womb to antiseizure medications and their potential impact on the brain of the developing child has long been researched. Despite this long period of... (Review)
Review
Exposure in the womb to antiseizure medications and their potential impact on the brain of the developing child has long been researched. Despite this long period of interest, this review highlights that above the well-known risks associated with valproate exposure, there are more data required for conclusions regarding all other antiseizure medications. Limited experience with phenytoin and phenobarbital in monotherapy makes clearly defining the risk to later child postnatal functioning difficult, although the evidence of an impact is stronger for phenobarbital than for phenytoin. The widely prescribed lamotrigine is limited in its investigation in comparison to unexposed control children, and whilst it has been demonstrated to carry a lower risk than valproate for certain outcomes, whether it is associated with a more moderate impact on wider aspects of neurodevelopmental functioning is still to be understood. Data for levetiracetam, topiramate and oxcarbazepine are too limited to confidently draw conclusions for most neurodevelopmental outcomes. This slow accumulation of evidence impacts on the safest use of medications in pregnancy and makes counseling women regarding the risks and benefits of specific antiseizure medications difficult. Improved focus, funding, and research methodologies are urgently needed.
Topics: Anticonvulsants; Child; Epilepsy; Female; Humans; Lamotrigine; Oxcarbazepine; Pregnancy; Pregnancy Complications
PubMed: 34279202
DOI: 10.2174/1570159X19666210716111814