Administration Of Carbamazepine Research Articles

Cost-effectiveness analysis of HLA-B*15:02 screening before treatment of epilepsy in Indonesia

IntroductionAdverse skin reactions due to drugs such as Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) occur in 3% of people receiving anti epileptic drugs (AED). Although SJS/TEN has a low incidence, the mortality and morbidity rates are high. Indonesia has not adopted HLA-B*1502 screening prior to administration of carbamazepine (CBZ), although previous studies found a relationship between HLA-B*1502 and SJS/TEN. MethodsA hybrid decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed focal epilepsy: CBZ direct therapy, levetiracetam (LEV) direct therapy, and therapy based on HLA-B*15:02 test results. From a societal perspective, base case and sensitivity analyses were carried out over a lifetime. ResultsDirect administration of CBZ appears to have a slightly lower average cost than the HLA-B*15:02 allele screening strategy. The increase in quality-adjusted life year (QALY) in HLA-B*15:02 screening before treatment related to the cost difference reached 0.519 with an incremental cost-effectiveness ratio (ICER) of around USD 984 per unit of QALY acquisition. Direct treatment of LEV increased treatment costs by almost USD 2000 on average compared to the standard CBZ strategy. The increase in QALY is 0.834 in direct levetiracetam treatment, with an ICER of around USD 2230 for each QALY processing. ConclusionCalculation of the cost-effectiveness of lifetime epilepsy therapy in this study found that the initial screening strategy with the HLA-B*15:02 test was the most cost-effective.

Evaluation of Lipid Emulsion-Mediated Sequestration and Redistribution of the Highly Lipophilic Carbamazepine in the Plasma of Rats

Aim: The idea that intravenous lipid emulsion (ILE) may serve as a "reservoir" for lipophilic drugs has emerged in research as an intravascular "lipid sink" effect. Carbamazepine (CBZ) is a widely used anticonvulsant. This compound has a neutral and highly lipophilic structure and can easily cross body membranes. In this study, our hypothesis focused on the potential efficacy of ILE in modulating blood carbamazepine concentrations. Material and Methods: 22 adult Sprague-Dawley rats were divided into four groups. All groups received CBZ at a dose of 20 mg/kg orogastrically. The first group was the control group. In the second group (activated charcoal group), activated charcoal (AC) was administered orogastrically at a dose of 1 g/kg five minutes after orogastric administration of carbamazepine. The third group (lipid group) received ILE at a dose of 3 ml/kg/min at the fifth minute. The fourth group was the saline group, in which 16 ml/kg of 0.9% NaCl was infused at the fifth minute. Blood samples of 0.5 ml were collected at 0, 4, 8, and 24 hours. Plasma was separated by centrifugation (4000 rpm, 10 minutes) and stored at -80oC for determination of CBZ concentrations. An Agilent 6410B HP-1200 LC series (USA) liquid chromatography system was used for analysis. Quantitative analysis was performed in the multiple reaction mode with electrospray positive ionization (ES+). Results: At the 8th hour of orogastric CBZ administration, CBZ concentration was significantly lower in the activated charcoal group than in the lipid and saline groups (p: 0.021; p: 0.023; p<0.05, respectively). There was no significant difference in CBZ concentrations between the other groups at 8 hours (p>0.05). In the lipid group, the increase in CBZ plasma concentrations was statistically significant at 4 and 8 hours compared to 0 hours (p: 0.005; p: 0.005, respectively). Conclusion: In the lipid group, plasma CBZ concentrations increased at 4 and 8 hours in plasma samples from which lipids were separated by differential centrifugation. In the lipid group, no effects favoring drug-lipid sequestration on the plasma distribution of CBZ were observed.

Isaacs Syndrome in A Patient with Positive CASPR2 And LGI1 Antibodies: A Case Report and Literature Review

Isaacs Syndrome (IS) is an autoimmune disease characterized by fasciculations, dysautonomia, and hyperactivity of muscle fibers due to hyperexcitability of the peripheral nerve system. Patients with IS often express voltage-gated potassium channels (VGKCs), contactin-associated protein 2 (CASPR2), and leucine-rich gliomainactivated protein (LGI1) antibodies. Slower rates of grouped fasciculation, known as myokymia, are a common presentation in IS patients. Recently, carbamazepine has been considered as the first-line treatment to alleviate the symptoms of IS patients. In this report, the authors present a case of a female patient with ramps and unintended movements in the abdomen and both lower limbs. She was diagnosed with IS after the detection of myokymia in the needle electromyography (EMG) and a positive paraneoplastic panel for CASPR2 and LGI antibodies. The patient is now symptom-free due to the administration of Carbamazepine, Gabapentin, and Baclofen. Additionally, due to her potential risk for solid tumors, she is under regular follow-up.

Standardized Centella asiatica extract ECa 233 alleviates pain hypersensitivity by modulating P2X3 in trigeminal neuropathic pain.

During oral surgery and temporomandibular joint repositioning, pain hypersensitivity often occurs due to irritation or inflammation of the nerve endings in the orofacial region. This study aimed to investigate the effects of ECa 233, a Centella asiatica-standardized extract, on the development of mechanical hyperalgesia and allodynia induced by chronic constriction injury of the infraorbital nerve in mice. The right infraorbital nerves of the mice were ligated. Oral carbamazepine (20 mg/kg) or ECa 233 (30, 100, or 300 mg/kg) was administered daily for 21 days. Von Frey and air-puff tests were performed on both sides of the whisker pad on days 0, 7, 14, and 21. Thereafter, the expression of purinergic receptor subtype 3 (P2X3) and voltage-gated sodium channel 1.7 (NaV1.7), a transmembrane protein, in the trigeminal ganglion and c-fos immunoreactivity-positive neurons in the trigeminal nucleus caudalis was assessed. After 21 days of infraorbital nerve ligation, the mice showed allodynia- and hyperalgesia-like behavior, P2X3 and NaV1.7 were upregulated in the trigeminal ganglion, and nociceptive activity increased in the trigeminal nucleus caudalis. However, the oral administration of carbamazepine (20 mg/kg), ECa 233 (100 mg/kg), or ECa 233 (300 mg/kg) mitigated these effects. Nevertheless, ECa 233 failed to affect NaV1.7 protein expression. Carbamazepine and ECa 233 can prevent pain hypersensitivity in mice. Considering the side effects of the long-term use of carbamazepine, ECa 233 monotherapy or combined ECa 233 and carbamazepine therapy can be used as an alternative for regulating the development of hypersensitivity in trigeminal pain. However, further detailed clinical studies should be conducted to provide comprehensive information on the use of ECa 233.

Contraindicated Drug Responses in Dravet Syndrome Brain Organoids Utilizing Micro Electrode Array Assessment Methods

Ensuring drug safety for patients with specific neurological disorders is of paramount importance. For instance, certain antiepileptic drugs (AEDs) are contraindicated in Dravet Syndrome (DS), which is characterized by a deficiency in Na+ channel function. Constructing in vitro assessment methods capable of detecting contraindicated drug responses and medication effects on neurons derived from DS patients is highly anticipated for drug safety assessment and therapeutic innovation. This study used micro electrode array (MEA) measurements with low-frequency analysis on human iPSC-derived DS organoids to investigate AED responses. When exposed to the contraindicated drugs carbamazepine and phenytoin, the number of network oscillations increased in DS organoids while maintaining oscillation intensity. Furthermore, carbamazepine administration appeared to enhance activities beyond oscillations which is partially consistent with findings in the DS mouse model. Conversely, treatment with the therapeutic drug sodium valproate resulted in a similar decrease in activity both in healthy and DS organoids. The frequency characteristics of spontaneous firings and AEDs responsiveness in DS organoids demonstrated partial correlation with typical electroencephalography patterns observed in vivo. In conclusion, this study, employing MEA measurements with low-frequency analysis, revealed contraindicated drug responses and disease-specific functional characteristics in DS organoids, effective for DS patient safety assessment, precision medicine, and antiepileptic drug screening.

Carbamazepine in Ventricular Extrasystoles Management: Clinical Case

Carbamazepine is a drug that has been used for a long time to treat various neurological and psychiatric disorders. The drug has effect on many body systems and, in particular, on the cardiovascular. The cardiovascular effect of carbamazepine depends on several factors such as the presence/absence of any comorbidities and its plasma concentration. The drug’s antiarrhythmic effect was demonstrated previously in a number of experimental and clinical studies. In this article, we would like to present the clinical case of pediatric patient with frequent ventricular extrasystoles and arrhythmogenic myocardial dysfunction. Several antiarrhythmic drugs were ineffective in this patient, while carbamazepine administration contributed to the decrease in ectopic activity up to minimal values.

Peculiarities of the effect of antiepileptic drugs on seizures in mice with corneal kindling against the background of low-dose premedication with carbamazepine and sulthiame

The aim. The aim of the study was to evaluate the effectiveness of antiepileptic drugs (AED) with a different mechanism of action against the background of prior use of low doses of carbamazepine and sultiam in the model of corneal kindling in mice. Materials and methods. The corneal kindling model in mice was used. The convulsive model was reproduced under the parallel preliminary administration of carbamazepine and sulthiame 30 minutes before electrostimulation. The anticonvulsant activity of AED (sulthiame, levetiracetam, carbamazepine, valproate, lamotrigine and retigabine) was studied under conditions after the formation of a stable syndrome of the generalised convulsive activity. Results and discussion. The administration of carbamazepine and sulthiame drugs modulates the activity of the cytochrome P450 enzyme system. Thus, carbamazepine in the dose of 7 and 12 mg/kg showed no significant anticonvulsant activity (the convulsive intensity – 4.42±0.25 points; 4.44±0.32 points) after its preliminary chronic administration, the same doses of carbamazepine showed a noticeable anticonvulsant effect in the control group of animals (3.52±0.26 points; 3.2±0.6 points, respectively). The anticonvulsant activity of lamotrigine changed both in the case of the preliminary chronic administration of an inducer (carbamazepine), and an inhibitor (sulthiame) of the cytochrome P450 system. Conclusion. Changes in the pharmacological effects of AED observed against the background of chronic administration of carbamazepine and sulthiame, in our opinion, may be due to both the modulation of the cytochrome P450 system and other groups of enzymes involved in the AED metabolism

Enhanced Brain Delivery via Intranasal Administration of Carbamazepine Loaded Solid Lipid Nanoparticles: Optimization, Pharmacokinetic Analysis, In-vitro, and In-vivo Drug Release Study.

Carbamazepine (Cbz) is the first-line drug for epileptic seizures but exhibits fluctuation at the plasma level and side effects after oral administration.To overcome these problems, Cbz should be targeted directly into the brain. Therefore, the current experimental design was aimed to formulate and optimize the Cbz containing solid lipid nanoparticles (SLNs) for brain delivery via intranasal administration to get rid of oral complications associated with Cbz. A full factorial design was performed to evaluate the effect of variables (X1 lipid concentration, X2 surfactant concentration, and X3 sonication time) on the response variables (size of nanoparticles, entrapment efficiency, and drug release). A two-level, three-factor design was employed herewith, and eight formulations were developed. Further, the formation of Cbz containing SLNs was characterized by compatibility, particle size, entrapment efficiency, and drug release with the support of Fourier Transform Infra-Red (FTIR), Zeta sizer, Transmission Electron Microscopy (TEM), Ultra-violet (U.V.), and High-Performance Liquid Chromatography (HPLC). All eight formulations were characterized through particle size, entrapment efficiency, and invitro drug release performance. Out of eight characterized formulations, SN1 showed the most promising results, including particle size of 210 ± 2.14 nm, entrapment efficiency of 42.1 ± 1.09%, and drug release of 61.3 ± 2.02% and considered an optimized batch. Additionally, the optimized batch SN1was further evaluated for an in-vivo study on male Wistar Rats. The study revealed that a high amount of drug was reached into the brain through intranasal administration compared to the intravenous route. Therefore, it can minimize the unwanted side effects of the Cbz associated with oral administration. The formulation SN1 possesses an excellent drug targeting efficiency of 3.014. Finally, the current experimental work concluded that there is a direct pathway from the intranasal route to the brain. This delivery system can be beneficial for directly delivering CNS-active drugs into the brain.

Driving performance of patients with epilepsy undergoing antiepileptic monotherapy

Driving performance of patients with epilepsy undergoing antiepileptic monotherapy

HLA-B*57:01/Carbamazepine-10,11-Epoxide Association Triggers Upregulation of the NFκB and JAK/STAT Pathways

Measure of drug-mediated immune reactions that are dependent on the patient's genotype determine individual medication protocols. Despite extensive clinical trials prior to the license of a specific drug, certain patient-specific immune reactions cannot be reliably predicted. The need for acknowledgement of the actual proteomic state for selected individuals under drug administration becomes obvious. The well-established association between certain HLA molecules and drugs or their metabolites has been analyzed in recent years, yet the polymorphic nature of HLA makes a broad prediction unfeasible. Dependent on the patient's genotype, carbamazepine (CBZ) hypersensitivities can cause diverse disease symptoms as maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms or the more severe diseases Stevens-Johnson-Syndrome or toxic epidermal necrolysis. Not only the association between HLA-B*15:02 or HLA-A*31:01 but also between HLA-B*57:01 and CBZ administration could be demonstrated. This study aimed to illuminate the mechanism of HLA-B*57:01-mediated CBZ hypersensitivity by full proteome analysis. The main CBZ metabolite EPX introduced drastic proteomic alterations as the induction of inflammatory processes through the upstream kinase ERBB2 and the upregulation of NFκB and JAK/STAT pathway implying a pro-apoptotic, pro-necrotic shift in the cellular response. Anti-inflammatory pathways and associated effector proteins were downregulated. This disequilibrium of pro- and anti-inflammatory processes clearly explain fatal immune reactions following CBZ administration.

Application of Teeth in Toxicological Analysis of Decomposed Cadavers Using a Carbamazepine-Administered Rat Model.

In a regular autopsy, blood and organs are used to quantify drug and toxicant concentrations; however, specimens such as blood cannot be collected from highly decomposed corpses, making the quantification of drug and toxicants impossible. This study aimed to estimate the blood carbamazepine (CBZ) concentration from teeth, a part of the human body that is best preserved after death. We sampled teeth and blood of rats administered CBZ. The correlation between the tooth and serum CBZ concentrations was analyzed. Rats were euthanized after CBZ administration and kept at 22 °C for 0 to 15 days before sampling the teeth and measuring the CBZ concentration. Undecalcified, fresh, frozen sections of rat teeth were prepared, and CBZ localization was evaluated. CBZ concentrations in both teeth and cardiac blood peaked at 60 min after administration and increased in a dose-dependent manner. CBZ concentration in teeth did not substantially change after death, with high CBZ distribution being observed in the pulp cavity. The tooth and serum CBZ concentrations were highly correlated, suggesting that the measurement of toxicant concentration in sampled teeth would allow for the estimation of blood toxicant concentration in highly decomposed corpses.

Effects of Carbamazepine on Cardiovascular System: Literature Review

Carbamazepine is an anticonvulsant that is commonly used in neurological and psychiatric patients to treat epileptic seizures, neuropathic pain, or bipolar disorder. Carbamazepine side effects, as well as side effects of many antiepileptic drugs, include cardiotoxic effects such as atrioventricular block, bradycardia, and cardiac rhythm disorders. However, carbamazepine has also been reported to have antiarrhythmic, normotimic, and membrane-stabilizing effects. This results in its administration to treat arrhythmias in children. Based on literature, carbamazepine administration as anti-arrhythmic drug is known in cases where the basic therapy was ineffective. The medication is not registered anywhere in the world for this purpose. Thus, it can be administered only off-label. The aim of our literature review is to analyze and summarize the existing data on carbamazepine effects on cardiovascular system, to determine its safety as anti-arrhythmic drug, and to describe various factors fostering its side effects.

CYP2D6 expression in the whole blood of epileptic patients in treatment with Carbamazepine

Carbamazepine (CBZ) is a commonly prescribed drug for patients with epilepsy. However, after administration of CBZ, many patients experience cutaneous adverse drug reactions (CADRs), the most common allergic skin symptoms. CYP2D6 enzyme is one of the enzymes that play an important role in drug metabolism in general and CBZ in particular. Therefore, analysis of gene expression and enzyme activity of CYP2D6will help predict the magnitude of CBZ metabolism of the patients, allowing them to forecast CADRs. In this study, the authors evaluated the mRNA expression of CYP2D6 in CBZ-treated epilepsy patients using a Real-time PCR method, and then investigated the relationship of CYP2D6 expression levels between mild and severe CADR harbouring groups. The results showed that the expression level of CYP2D6 in the CBZ-tolerant group was about 3 times higher than that in the CBZ-allergic group. These results suggested that the gene expression level of CYP2D6 could be a useful biomarker for predicting CBZ response in patients with epilepsy.

Effect of Antiepileptics on Retinal Blood Flow in Adults Wister Rats

Background: Carbamazepine (CBZ) is an effective antiepileptic drug (AED) used as first line of drug for of partial and convulsive generalized epilepsy in all age groups. Most common clinically reported side effect of CBZ is blurry or double vision. How it affects retinal histological architecture has not been explored yet. Aim: To observe the light microscopic retinal changes in adult Wistar albino rats after administration of CBZ. Methods: The experiment was conducted in University of Health Sciences, Lahore after the approval of ethical review committee. 18 Rats were randomly divided into 3 groups of 6 rats each. Group A served as control and was given 1ml saline alkalinized with 0.1N NaOH, Group B&C were given CBZ 50 mg/kg and 100 mg/kg respectively dissolved in 1ml saline alkalinized with 0.1N NaOH in 3 divided doses intraperitoneally for 7 days. Animals were sacrificed on 8th day, and retinal tissue sections of 5µm were stained for H& E to look for vascular congestion in retinal layers (yes/no). Chi2 was applied for statistical analysis using SPSS v 20. Practical implications: ophthalmic examination mandatory for epileptic patients on long term use of AED. Results: vascular congestion was seen among layers of retina in dose dependent manner in experimental groups (p=0.006) Conclusion: The findings of the present study indicates that CBZ affects retina blood flow, can impose a potential risk to visual disturbances. Key words: vascular congestion, epilepsy, carbamazepine (CBZ)

Rosemary and CoQ10 Alleviated the Detrimental Effects of Concomitant Administration of Acetaminophen and Carbamazepine by Accelerating Their Metabolism and Elimination

BACKGROUND: The interaction of carbamazepine (CBZ) and acetaminophen (APAP) could result in hepatic failure and mortality. This study was conducted to analyzed the potential of rosemary ethanol extract (REE) or coenzyme Q10 (CoQ10) to alleviate the interactions between CBZ and APAP.METHODS: Fourty-eight adult male rats were treated differently based on the assigned groups. Oxidative stress parameters, including malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase, and glutathione S-transferase (GST), and the expression levels of CYP3A4, CYP2E1, IL-6, TNF-α, and IL-1B in the liver were estimated. In addition, the histopathology of liver was examined and the plasma clearance rate of CBZ and APAP was estimated.RESULTS: Combination of CBZ and APAP significantly elevated alanine aminotransferase (ALT) activity and hepatic MDA, and reduced the activities of GPx, GST, and GSH level in liver. The gene expression of CYP3A4 and CYP2E1 was upregulated by CBZ and CoQ10, respectively. The expression of IL-6 has decreased in the groups treated with CBZ alone or in combination with APAP. TNF-α expression was significantly downregulated in the groups treated with CBZ, APAP, REE, CoQ10, or combination CBZ and APAP. The liver from CBZ and APAP combination group showed centrolobular degeneration and necrosis. REE and CoQ10 were able to alleviate most of these detrimental effects. The combined administration of CBZ and APAP extended the plasma clearance time of APAP and CBZ from 6 to 24 and from 9 to 24 hours, respectively.CONCLUSION: REE and CoQ10 alleviated the detrimental effects of the combination of CBZ and APAP through enhancing the cellular antioxidant milieu, induction of metabolizing enzymes, reduction of the plasma half-life of APAP and CBZ preventing their accumulation and potential interaction.KEYWORDS: acetaminophen, antioxidants, carbamazepine, CoQ10, CYP3A4, CYP2E1, glutathione, lipid peroxidation, rosemary

MULTIDISCIPLINARY APPROACH IN A PATIENT WITH SD22Q11 DELETION SYNDROME: CASE REPORT

The 22q11.2 deletion syndrome (SD22q11), known as Digeorge syndrome, has a wide phenotypic spectrum with more than 180 clinical signs described in the literature, related to both physical and behavioral aspects, which makes the diagnosis challenging in relation to the condition. The 22q11.2 microdeletion is detected only by molecular genetic techniques such as comparative hybridization of 2 DNA samples. A 13-year-old female patient diagnosed with SD22q11 was referred for specialized dental care for special patients. During anamnesis, heart disease; immunologic, hematologic, neurocognitive, psychiatric disorders; and craniofacial malformation were reported, characteristics consistent with the syndrome in question. Dental procedures, such as extractions and endodontic accesses, were made possible through the medical report of the analysis of systemic conditions, associated with periodic complementary exams. Neurologic management through the administration of carbamazepine and valproic acid was essential to reduce hallucinations while in the dental chair.

Treatment of Canine Idiopathic Epilepsy - Clinical Picture after Drug Interaction

Background: The large number of diseases demand perennial development of the pharmaceutical industry. The drug-testing phase is essential to make them available safely. Awareness of pharmacological properties, adverse effects and drug interactions is required. Drug interactions are common in veterinary medicine and should be avoided. At times, epileptic seizures require polydrug therapy, predisposing patients to drug interactions. The interaction between carbamazepine and phenobarbital reported in the literature is an example. The aim of this paper is to report a clinical picture of drug interaction in the treatment of idiopathic epilepsy. Case: A 1-year-old Border Collie male dog, was admitted at the Veterinary Hospital of the Federal University of Lavras in post-ictal. The tutor reported that a year ago the animal had epileptic seizures and clusters with intervals of 21 to 25 days. Despite the continued use of previously prescribed phenobarbital (7.4 mg/kg, v.o., BID, until new recommendations) and carbamazepine (7.5 mg/kg, v.o., BID, until new recommendations), seizure control was not achieved. The physical examination indicated, tachypnea, ptialism, mydriasis, intense fatigue, and alienation from the environment. The patient did not respond to the threat-reflex test. Blood count, hepatic and renal blood chemistry, serum electrolyte (potassium, sodium, calcium and phosphorus), and phenobarbital dosages were requested. Based on the animal's history, breed characteristics, and alterations in the physical examination associated with normal results in complementary exams, idiopathic epilepsy was diagnosed. After analyzing the case, it was observed that the inefficiency in the control of seizures was possibly due to the drug interaction between phenobarbital and carbamazepine. Carbamazepine and phenobarbital reciprocally reduce their half-lives. To confirm the raised hypothesis, the serum concentration of carbamazepine was gradually reduced through weaning from its dose administered to the patient. Serial dosage of the concentration of phenobarbital in the bloodstream was performed. As a result, the serum phenobarbital, previously dosed at a concentration of 13.3 mg/dL with concomitant administration of carbamazepine, increased to 22 mg/dL 40 days after the beginning of weaning from carbamazepine (T0), and then to 36 mg/dL 100 days after T0. There was an increase in the concentration of phenobarbital in the bloodstream while the serum concentration of carbamazepine declined. The patient spaced out his seizures to every 50 to 60 days with phenobarbital monotherapy at a dose of 6 mg/kg. Discussion: Efficient control of clusters, such as the reduction of seizures by 50%, was only possible due to the meticulous perception of the possible interaction reported in medicine. Carbamazepine and phenobarbital are P450 isoenzyme inducers. The concomitant administration of both drugs potentiated the action of isoenzymes in the hepatic microsomal system, which led to an accelerated metabolic processing of the drugs. After weaning from carbamazepine, that is, reducing the action of carbamazepine on the isoenzymes of the P450 enzyme system, the concentration of phenobarbital normalized at 36 mg/dL. Such concentration is within the reference range reported in the literature: 25 mg/dL to 35 mg/dL of serum phenobarbital for treatment efficacy. Therefore, the control of convulsive crises was achieved. The increase in the concentration of phenobarbital due only to weaning from carbamazepine, even after decreasing the daily dose of barbiturate prescribed to the animal, contributed to evidence of the interaction of these drugs. It is noted that prior knowledge of pharmacological properties, careful study of the patient's history, and the cooperation of the tutor were essential for the therapeutic success and practice of evidence-based veterinary medicine. Keywords: drug interaction, carbamazepine, phenobarbital, P450 enzyme. Título: Tratamento da epilepsia idiopática canina - quadro clínico após interação medicamentosa. Descritores: interação medicamentosa, carbamazepina, fenobarbital, enzima P450.

Trigeminal neuropathy after tozinameran vaccination against COVID-19 in postmicrovascular decompression for trigeminal neuralgia: illustrative case.

BACKGROUNDVaccines against coronavirus disease 2019 have a high level of efficacy and safety across all populations. However, numerous case series have been published on neurological disorders, including Bell’s palsy, Guillain-Barre syndrome, transverse myelitis, and multiple sclerosis. The authors presented a case of trigeminal neuropathy after coronavirus vaccination in a patient who had undergone microvascular decompression (MVD) for trigeminal neuralgia (TN).OBSERVATIONSA 77-year-old woman presented with acute trigeminal neuropathy after receiving a Pfizer-BioNtech vaccination (tozinameran) against severe acute respiratory syndrome coronavirus 2. The patient had undergone MVD for TN and the facial pain completely disappeared. One month later, she received the first injection of the tozinameran vaccine. Twelve hours after vaccination, she presented with numbness and pain induced by touching any place on the entire right face. No eruption was observed on her face. The serum herpes zoster virus antibodies were confirmed within the normal range. Magnetic resonance imaging revealed no abnormalities. The authors suspected a right trigeminal neuropathy after vaccination. Administration of carbamazepine and pregabalin improved TN but facial numbness persisted, especially in the mandibular division.LESSONSThe coronavirus is a possible etiology of secondary trigeminal neuropathy in the case of MVD for TN.

Influence of concurrent and staggered dosing of semi-solid nutrients on the pharmacokinetics of orally administered carbamazepine in rats.

In the present study, we examined the effects of concurrent and staggered dosing of PG-soft ace-MP TM (PG), novel semi-solid enteral nutrients, on the pharmacokinetics of orally administered carbamazepine (CBZ) in rats due to the high possibility of drug interaction during the absorption process. The pharmacokinetic behavior of CBZ was considerably altered when administered concurrently with PG. The maximum serum CBZ concentration (Cmax) significantly decreased and the mean residence time (MRT) significantly increased. The elimination constant (ke) also significantly increased, but there were no significant changes in the area under the serum CBZ concentration versus time curve (AUC) and the time to reach Cmax (Tmax). However, these changes in the pharmacokinetic parameters were eliminated by waiting 20 min, the time interval equivalent to the Tmax described above, between CBZ administration and PG dosing. This study suggested that PG interferes with CBZ absorption from the digestive tract, although staggered administration of CBZ and PG prevented their interaction.

Correlation between Level of Serum Transaminases and Duration of Antiepileptic Drugs in Epilepsy Children in Sanglah Hospital

BACKGROUND: Some antiepileptic drugs (AEDs), particularly sodium valproate, phenytoin, phenobarbital, and carbamazepine induce and increase production of hepatic enzymes. The adverse metabolic effects of AEDs treatments have become main concern, however data about evaluation of serum transaminases and duration of AEDs in Indonesia still limited. AIM: The aim of the study was to investigate correlation of AEDs and serum transaminases in children with epilepsy. METHODS: This cross-sectional research was conducted in pediatric neurology outpatient clinic in Sanglah Hospital. The target was children with epilepsy who had taken AEDs for at least 6 months. Data were collected from January 2020 to the number of samples were achieved. The exclusion criteria were concomitant liver disease, taking drugs which induce elevated serum transaminase or alcohol abuse. Data including age, gender, nutritional status, type, and duration of AEDs were obtained from medical record. Correlation was analyzed by Pearson’s or Spearman’s correlation, p < 0.05 was considered significant. RESULTS: Total 148 epileptic children enrolled in this study. Aspartate transaminase (AST) and alanine aminotransferase (ALT) level were highest in the group receiving combination therapy (34.37 ± 24.9 U/L and 35.96 ± 23.3 U/L). There was a significant negative correlation between duration of carbamazepine and AST (r = –0.723, p = 0.0001) and ALT (r = –0.457, p = 0.009), as well as duration of valproic acid with AST and ALT (r = –0.689 and –0.677, p = 0.0001). Duration of phenobarbital administration was positively correlated with AST and ALT (r = 0.546 and 0.425, p = 0.0001). Combination therapy also had positive correlation with AST and ALT (r = 0.815 and 0.781, p = 0.0001, respectively). CONCLUSION: Duration administration of carbamazepine and valproic acid had negative correlation with AST and ALT; however, phenobarbital and combination therapy were positively correlated with AST and ALT.