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Clinical Case Reports Oct 2023Drug-induced gingival overgrowth can occur as a side effect of specific drugs and lead to poor oral function. Appropriate dental management of the overgrowth may improve...
Drug-induced gingival overgrowth can occur as a side effect of specific drugs and lead to poor oral function. Appropriate dental management of the overgrowth may improve oral function and improve cognitive deficits after cerebrovascular accidents.
PubMed: 37881202
DOI: 10.1002/ccr3.8093 -
Epilepsy Research Nov 2023This retrospective chart review examined dose reductions and discontinuations of concomitant antiseizure medications (ASMs) following cenobamate initiation and...
This retrospective chart review examined dose reductions and discontinuations of concomitant antiseizure medications (ASMs) following cenobamate initiation and maintenance in patients with epilepsy treated at MetroHealth (Cleveland, OH) between 9/1/2020-9/26/2022. Concomitant ASM dose adjustments and treatment-emergent adverse events (TEAEs) were assessed. Efficacy (100 % seizure reduction) was examined among patients who received cenobamate for ≥ 3 months at data cutoff (including titration). As of 9/26/2022, 95 patients received cenobamate (mean age, 45.9 years; 48.4 % female, median exposure 7.5 months). Five patients (5.3 %) discontinued (n = 1 withdrawal by patient; n = 1 noncompliance; n = 3 adverse event). Among the 90 patients taking cenobamate at data cutoff, 50 % (45/90) discontinued ≥ 1 concomitant ASM, most commonly clobazam (n = 18), levetiracetam (n = 10), and phenytoin (n = 7); 21 patients (23.3 %) had additional concomitant ASM dose reductions, most commonly phenytoin (n = 6) and clobazam (n = 4). Sixteen patients received cenobamate monotherapy. Among 79 patients who received cenobamate for ≥ 3 months at data cutoff, 51.9 % (41/79) were seizure-free for ≥ 3 months. Of the 41 seizure-free patients, 58.5 % (24/41) were taking 100 mg/day of cenobamate. Sixteen of the 95 cenobamate-treated patients (16.8 %) reported 22 TEAEs. The most common TEAE was fatigue (n = 7). These data suggest that cenobamate therapy may allow reduction or elimination of polytherapy in some patients.
Topics: Humans; Female; Middle Aged; Male; Drug Tapering; Retrospective Studies; Clobazam; Phenytoin; Anticonvulsants; Treatment Outcome
PubMed: 37871541
DOI: 10.1016/j.eplepsyres.2023.107242 -
Pharmacological Reports : PR Dec 2023Overwhelming evidence indicates that some naturally occurring coumarins and terpenes are widely used in folk medicine due to their various therapeutic effects affecting...
Anticonvulsant effects of isopimpinellin and its interactions with classic antiseizure medications and borneol in the mouse tonic-clonic seizure model: an isobolographic transformation.
BACKGROUND
Overwhelming evidence indicates that some naturally occurring coumarins and terpenes are widely used in folk medicine due to their various therapeutic effects affecting the brain. Antiseizure medications (ASMs) are the principal treatment option for epilepsy patients, although some novel strategies based on naturally occurring substances are intensively investigated. This study was aimed at determining the influence of isopimpinellin (ISOP-a coumarin) when administered either separately or in combination with borneol (BOR-a monoterpenoid), on the antiseizure potencies of four classic ASMs (carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and valproate (VPA)) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures.
MATERIALS
Tonic-clonic seizures were evoked experimentally in mice after systemic (ip) administration of the respective doses of ISOP, BOR, and classic ASMs. Interactions for two-drug (ISOP + a classic ASM) and three-drug (ISOP + BOR + a classic ASM) mixtures were assessed isobolographically in the mouse MES model.
RESULTS
ISOP (administered alone) had no impact on the anticonvulsant potencies of four classic ASMs. Due to the isobolographic transformation of data, the combination of ISOP + VPA exerted an antagonistic interaction, whereas the two-drug mixtures of ISOP + CBZ, ISOP + PHT, and ISOP + PB produced additive interactions in the mouse MES model. The three-drug combinations of ISOP + BOR with CBZ and PHT produced additive interactions, while the three-drug combinations of ISOP + BOR with PB and VPA exerted synergistic interactions in the mouse MES model.
CONCLUSIONS
The most intriguing interaction was that for ISOP + VPA, for which the addition of BOR evoked a transition from antagonism to synergy in the mouse MES model.
Topics: Humans; Animals; Mice; Anticonvulsants; Drug Interactions; Seizures; Carbamazepine; Phenobarbital; Phenytoin; Electroshock; Drug Combinations; Disease Models, Animal; Dose-Response Relationship, Drug
PubMed: 37821793
DOI: 10.1007/s43440-023-00532-x -
Cureus Sep 2023The administration of multiple antiepileptic drugs (AEDs) is standard practice for neurological intensive care unit (ICU) patients who cannot obtain seizure control with... (Review)
Review
The administration of multiple antiepileptic drugs (AEDs) is standard practice for neurological intensive care unit (ICU) patients who cannot obtain seizure control with monotherapy. Phenytoin and levetiracetam continue to be highly utilized AEDs for ICU patients due to their efficacy and relatively low cost. However, there is no randomized control trial to date that assesses the efficacy outcomes of the concurrent use of these two medications for ICU patients in convulsive or silent status epilepticus that combats the toxicity with increasing dosages of a single drug by itself. Here, we have analyzed several studies published over the past two decades to better understand whether the concomitant use of these two medications is more efficacious in treating unremitting seizures in ICU patients. Several factors influence which AED is a better fit for ICU patients due to the complexity of their clinical state. Risk for drug interactions, increased incidence of renal and hepatic impairment, and higher need for patient monitoring are daily barriers that determine AED use. After analysis of past research, while the efficacy of concurrent use of levetiracetam and phenytoin is still not fully clear, we offer the "Arrowhead Rationale" for such dual therapy in a subset of patients at our tertiary care trauma and stroke center in Southern California.
PubMed: 37790049
DOI: 10.7759/cureus.44547 -
Journal of Pharmaceutical Health Care... Oct 2023In-hospital therapeutic drug monitoring (TDM) requires a suitable quantification method for target drugs from the viewpoint of precision, throughput, and testing costs....
BACKGROUND
In-hospital therapeutic drug monitoring (TDM) requires a suitable quantification method for target drugs from the viewpoint of precision, throughput, and testing costs. We previously developed a practical HPLC-UV platform for quantification of serum levels of various drugs. In this report, the platform was effectively applied to the quantification of patient serum levels of five different drugs by clinical professionals in our hospital during their daily work.
METHODS
The residual sera of patients receiving carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), vancomycin (VCM), or voriconazole (VRCZ) were used in the present clinical study. The quantification method for each drug consisted of rapid solid-phase extraction (SPE) of each drug in the patient serum, followed by optimized HPLC-UV analysis of the drug in the SPE eluate. Furthermore, patient serum levels of PHT, CBZ, and VCM were also measured by ligand-binding assay using a cobas analyzer in our hospital, and those of LTG and VRCZ were measured by HPLC-MS/MS at an outsourced provider. Passing-Bablok regression analysis and Bland-Altman analysis were employed to analyze the agreement of drug levels in patient sera, which was separately quantified using two different methods-our HPLC-UV platform and the cobas analyzer, or HPLC-UV and HPLC-MS/MS.
RESULTS
All analytical conditions of the present method using our HPLC-UV platform were well optimized for each target drug quantification in the patient's serum, and the quantification method for each drug was fully validated for accuracy, precision and reproducibility. Furthermore, Passing-Bablok regression analysis and Bland-Altman analysis revealed that patient serum levels of PHT, CBZ, and VCM quantified by our HPLC-UV platform were closely correlated with those quantified by the cobas analyzer, and the levels of LTG and VRCZ quantified by our HPLC-UV platform were also correlated with those quantified by HPLC-MS/MS.
CONCLUSIONS
Our HPLC-UV platform can be performed without requiring special analytical techniques. This platform is expected to be used for the measurement of blood levels of multiple drugs for in-hospital routine TDM.
PubMed: 37777811
DOI: 10.1186/s40780-023-00298-7 -
Epilepsy & Behavior : E&B Nov 2023This study evaluated the impact of a newly established clinic for the diagnosis of pediatric epilepsy in a resource-limited center (Ifakara, Tanzania). (Observational Study)
Observational Study
PURPOSE
This study evaluated the impact of a newly established clinic for the diagnosis of pediatric epilepsy in a resource-limited center (Ifakara, Tanzania).
METHODS
Patients aged 0-18 years referred to the Pediatric Epilepsy Unit of Saint Francis Referral Hospital were recruited. Demographic and clinical data were collected through Kobo Toolbox and analyzed through a descriptive analysis..
RESULTS
143 patients were evaluated, and for 48 of them an EEG was recorded (abnormalities were detected in 80.85% of the cases). The diagnosis of epilepsy was confirmed in 87 patients. Focal epilepsy was diagnosed in 57 patients, generalized epilepsy in 24 patients, and forms of unknown onset in 6 patients. Epilepsy was excluded for 9 children. Etiologies included hypoxic-ischemic encephalopathy (39%), central nervous system infections (3.4%), and genetic diseases (3.4%). A specific epilepsy syndrome was diagnosed in 16 patients. 74 patients were under treatment; the most used antiseizure medication (ASM) was phenobarbital (43.36%), followed by carbamazepine (16.08%), sodium valproate (11.19%), phenytoin (2.8%), and lamotrigine (0.7%). Therapeutic changes were proposed to 95 patients, more frequently consisting of withdrawing phenobarbital (39.16%), switching to sodium valproate (27.97%), switching to or adjusting carbamazepine dosage (27.27%), and starting prednisone (2.8%). 76% of the patients with confirmed epilepsy achieved complete seizure freedom at the fourth follow-up consultation.
CONCLUSIONS
Our data depicted the epilepsy spectrum and highlighted the prognostic implications of improving the availability of ASMs such as sodium valproate and second- and third-generation ones in resource-limited countries.
Topics: Child; Humans; Valproic Acid; Tanzania; Epilepsy; Anticonvulsants; Carbamazepine; Phenobarbital; Benzodiazepines
PubMed: 37776594
DOI: 10.1016/j.yebeh.2023.109454 -
Pharmaceutics Aug 2023Therapeutic drug monitoring (TDM) is the clinical practice of measuring drug concentrations. TDM can be used to determine treatment efficacy and to prevent the...
Therapeutic drug monitoring (TDM) is the clinical practice of measuring drug concentrations. TDM can be used to determine treatment efficacy and to prevent the occurrence or reduce the risk of drug-induced side effects, being, thus, a tool of personalized medicine. Drugs for which TDM is applied should have a narrow therapeutic range and exhibit both significant pharmacokinetic variability and a predefined target concentration range. The aim of our study was to assess the current status of TDM in Greek public hospitals and estimate its progress over the last 20 years. All Greek public hospitals were contacted to provide data and details on the clinical uptake of TDM in Greece for the years 2003 and 2021 through a structured questionnaire. Data from 113 out of 132 Greek hospitals were collected in 2003, whereas for 2021, we have collected data from 98 out of 122 hospitals. Among these, in 2003 and 2021, 64 and 51 hospitals, respectively, performed TDM. Antiepileptics and antibiotics were the most common drug categories monitored in both years. The total number of drug measurement assays decreased from 2003 to 2021 (153,313 ± 7794 vs. 90,065 ± 5698; = 0.043). In direct comparisons between hospitals where TDM was performed both in 2003 and 2021 (n = 35), the mean number of measurements was found to decrease for most drugs, including carbamazepine (198.8 ± 46.6 vs. 46.6 ± 10.1, < 0.001), phenytoin (253.6 ± 59 vs. 120 ± 34.3; = 0.001), amikacin (147.3 ± 65.2 vs. 91.1 ± 71.4; = 0.033), digoxin (783.2 ± 226.70 vs. 165.9 ± 28.9; < 0.001), and theophylline (71.5 ± 28.7 vs. 11.9 ± 6.4; = 0.004). Only for vancomycin, a significant increase in measurements was recorded (206.1 ± 96.1 vs. 789.1 ± 282.8; = 0.012). In conclusion, our findings show that TDM clinical implementation is losing ground in Greek hospitals. Efforts and initiatives to reverse this trend are urgently needed.
PubMed: 37765152
DOI: 10.3390/pharmaceutics15092181 -
The Cochrane Database of Systematic... Aug 2023Prenatal exposure to certain anti-seizure medications (ASMs) is associated with an increased risk of major congenital malformations (MCM). The majority of women with... (Review)
Review
BACKGROUND
Prenatal exposure to certain anti-seizure medications (ASMs) is associated with an increased risk of major congenital malformations (MCM). The majority of women with epilepsy continue taking ASMs throughout pregnancy and, therefore, information on the potential risks associated with ASM treatment is required.
OBJECTIVES
To assess the effects of prenatal exposure to ASMs on the prevalence of MCM in the child.
SEARCH METHODS
For the latest update of this review, we searched the following databases on 17 February 2022: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to February 16, 2022), SCOPUS (1823 onwards), and ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP). No language restrictions were imposed.
SELECTION CRITERIA
We included prospective cohort controlled studies, cohort studies set within pregnancy registries, randomised controlled trials and epidemiological studies using routine health record data. Participants were women with epilepsy taking ASMs; the two control groups were women without epilepsy and untreated women with epilepsy.
DATA COLLECTION AND ANALYSIS
Five authors independently selected studies for inclusion. Eight authors completed data extraction and/or risk of bias assessments. The primary outcome was the presence of an MCM. Secondary outcomes included specific types of MCM. Where meta-analysis was not possible, we reviewed included studies narratively.
MAIN RESULTS
From 12,296 abstracts, we reviewed 283 full-text publications which identified 49 studies with 128 publications between them. Data from ASM-exposed pregnancies were more numerous for prospective cohort studies (n = 17,963), than data currently available for epidemiological health record studies (n = 7913). The MCM risk for children of women without epilepsy was 2.1% (95% CI 1.5 to 3.0) in cohort studies and 3.3% (95% CI 1.5 to 7.1) in health record studies. The known risk associated with sodium valproate exposure was clear across comparisons with a pooled prevalence of 9.8% (95% CI 8.1 to 11.9) from cohort data and 9.7% (95% CI 7.1 to 13.4) from routine health record studies. This was elevated across almost all comparisons to other monotherapy ASMs, with the absolute risk differences ranging from 5% to 9%. Multiple studies found that the MCM risk is dose-dependent. Children exposed to carbamazepine had an increased MCM prevalence in both cohort studies (4.7%, 95% CI 3.7 to 5.9) and routine health record studies (4.0%, 95% CI 2.9 to 5.4) which was significantly higher than that for the children born to women without epilepsy for both cohort (RR 2.30, 95% CI 1.47 to 3.59) and routine health record studies (RR 1.14, 95% CI 0.80 to 1.64); with similar significant results in comparison to the children of women with untreated epilepsy for both cohort studies (RR 1.44, 95% CI 1.05 to 1.96) and routine health record studies (RR 1.42, 95% CI 1.10 to 1.83). For phenobarbital exposure, the prevalence was 6.3% (95% CI 4.8 to 8.3) and 8.8% (95% CI 0.0 to 9277.0) from cohort and routine health record data, respectively. This increased risk was significant in comparison to the children of women without epilepsy (RR 3.22, 95% CI 1.84 to 5.65) and those born to women with untreated epilepsy (RR 1.64, 95% CI 0.94 to 2.83) in cohort studies; data from routine health record studies was limited. For phenytoin exposure, the prevalence of MCM was elevated for cohort study data (5.4%, 95% CI 3.6 to 8.1) and routine health record data (6.8%, 95% CI 0.1 to 701.2). The prevalence of MCM was higher for phenytoin-exposed children in comparison to children of women without epilepsy (RR 3.81, 95% CI 1.91 to 7.57) and the children of women with untreated epilepsy (RR 2.01. 95% CI 1.29 to 3.12); there were no data from routine health record studies. Pooled data from cohort studies indicated a significantly increased MCM risk for children exposed to lamotrigine in comparison to children born to women without epilepsy (RR 1.99, 95% CI 1.16 to 3.39); with a risk difference (RD) indicating a 1% increased risk of MCM (RD 0.01. 95% CI 0.00 to 0.03). This was not replicated in the comparison to the children of women with untreated epilepsy (RR 1.04, 95% CI 0.66 to 1.63), which contained the largest group of lamotrigine-exposed children (> 2700). Further, a non-significant difference was also found both in comparison to the children of women without epilepsy (RR 1.19, 95% CI 0.86 to 1.64) and children born to women with untreated epilepsy (RR 1.00, 95% CI 0.79 to 1.28) from routine data studies. For levetiracetam exposure, pooled data provided similar risk ratios to women without epilepsy in cohort (RR 2.20, 95% CI 0.98 to 4.93) and routine health record studies (RR 0.67, 95% CI 0.17 to 2.66). This was supported by the pooled results from both cohort (RR 0.71, 95% CI 0.39 to 1.28) and routine health record studies (RR 0.82, 95% CI 0.39 to 1.71) when comparisons were made to the offspring of women with untreated epilepsy. For topiramate, the prevalence of MCM was 3.9% (95% CI 2.3 to 6.5) from cohort study data and 4.1% (0.0 to 27,050.1) from routine health record studies. Risk ratios were significantly higher for children exposed to topiramate in comparison to the children of women without epilepsy in cohort studies (RR 4.07, 95% CI 1.64 to 10.14) but not in a smaller comparison to the children of women with untreated epilepsy (RR 1.37, 95% CI 0.57 to 3.27); few data are currently available from routine health record studies. Exposure in utero to topiramate was also associated with significantly higher RRs in comparison to other ASMs for oro-facial clefts. Data for all other ASMs were extremely limited. Given the observational designs, all studies were at high risk of certain biases, but the biases observed across primary data collection studies and secondary use of routine health records were different and were, in part, complementary. Biases were balanced across the ASMs investigated, and it is unlikely that the differential results observed across the ASMs are solely explained by these biases.
AUTHORS' CONCLUSIONS
Exposure in the womb to certain ASMs was associated with an increased risk of certain MCMs which, for many, is dose-dependent.
Topics: Pregnancy; Child; Female; Humans; Male; Prospective Studies; Topiramate; Lamotrigine; Phenytoin; Cohort Studies; Prenatal Exposure Delayed Effects; Epilepsy
PubMed: 37647086
DOI: 10.1002/14651858.CD010224.pub3 -
Cureus Jul 2023Toxic epidermal necrolysis (TEN) is a rare fatal mucocutaneous blistering disorder that can have varied underlying triggers. The percentage of body surface area (BSA)...
Toxic epidermal necrolysis (TEN) is a rare fatal mucocutaneous blistering disorder that can have varied underlying triggers. The percentage of body surface area (BSA) that is impacted by erosive blistering is what separates it from Steven Johnson syndrome (SJS), both of which have the same underlying pathogenesis and are thought to exist on a continuum of disease with TEN being the more serious of the two. Medications are the most frequent cause of TEN/SJS and typically cause disease in both adults and children within eight weeks; however, the median exposure window is four days to four weeks. Nonsteroidal anti-inflammatory drugs, allopurinol, anticonvulsants including lamotrigine, phenytoin, levetiracetam and carbamazepine, antimicrobial sulfonamides, and the antiviral nevirapine are examples of medications that frequently cause TEN/SJS. Here, we are reporting a case of phenytoin-induced TEN highlighting the patient's excellent response to immunomodulating treatment despite 100% involvement of the BSA.
PubMed: 37644929
DOI: 10.7759/cureus.42654