Acute Seizures Due to a Probable Interaction between Valproic Acid and Meropenem

2005 ◽  
Vol 39 (3) ◽  
pp. 533-537 ◽  
Author(s):  
Francisco Javier Coves-Orts ◽  
Joaquín Borrás-Blasco ◽  
Andrés Navarro-Ruiz ◽  
Ana Murcia-López ◽  
Francisco Palacios-Ortega
Keyword(s):  
Valproic Acid ◽  
Serum Concentration ◽  
Epileptic Seizures ◽  
Clonic Seizure ◽  
Experimental Models ◽  
Tonic Clonic Seizure ◽  
Serum Concentrations ◽  
Intensive Care Unit Treatment ◽  
Acute Seizures ◽  
Probable Interaction

OBJECTIVE: To report a probable interaction between meropenem and valproic acid that resulted in the development of epileptic seizures. CASE SUMMARY: A 21-year-old woman presented to our emergency department because of a new-onset, generalized tonic—clonic seizure and was admitted to the intensive care unit. Treatment with valproic acid 1000 mg as a continuous intravenous infusion over 24 hours was initiated. On day 6, the serum concentration of valproic acid was 52.5 μg/mL. On day 13, treatment with intravenous meropenem 1 g 3 times daily was started. On day 15, when the patient was afebrile, numerous myoclonic episodes occurred involving her arms and face; the serum concentration of valproic acid at that time was 42 μg/mL. The valproic acid dose was increased to 2880 mg. Two days later, a generalized tonic—clonic seizure occurred despite the increased dosage, and the plasma concentration of valproic acid fell to 7 μg/mL. The valproic acid dose was increased the following day to 3600 mg; however, the serum concentrations remained <10 μg/mL. On day 19, based on the results of a blood culture and the suspicion of an interaction between meropenem and valproic acid, meropenem therapy was suspended. The serum concentration of valproic acid was 52.4 μg/mL on day 27. Three days later, the patient was asymptomatic and was discharged. DISCUSSION: Coadministration of valproic acid and other drugs that are metabolized by the hepatic cytochrome P450 isoenzyme system can lead to clinically relevant interactions by induction or inhibition of enzymes in shared metabolic pathways. In view of studies in experimental models, the interaction between carbapenem antibiotics and valproic acid is at least possible. Use of the Naranjo probability scale indicated a probable relationship between acute seizures and a meropenem—valproic acid interaction in this patient. CONCLUSIONS: This case report provides strong evidence for an interaction between valproic acid and meropenem. Clinicians should be aware of this potential interaction that may be associated with a serious adverse effect as the result of the decrease of the valproic acid serum concentrations.

scholarly journals Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

2019 ◽  
Vol 65 (9) ◽  
pp. 1188-1192
Author(s):  
Erkan Kilinc ◽  
Handan Gunes
Keyword(s):  
Interleukin 1 ◽  
Plasma Concentrations ◽  
Onset Time ◽  
Epileptic Seizures ◽  
Clonic Seizure ◽  
Tonic Clonic Seizure ◽  
Interleukin 1 Beta ◽  
Calcitonin Gene ◽  
Epilepsy Treatment ◽  
Dual Action

SUMMARY OBJECTIVE We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1β) in pentylenetetrazol-induced seizures in rats. METHODS Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine’s scale, and plasma CGRP, SP, and IL-1β concentrations were measured using ELISA. RESULTS Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1β concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1β concentrations. However, obestatin did not change CGRP, SP, and IL-1β concentrations. CONCLUSION Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.

Elevated Free Fractions of Valproic Acid in a Heart Transplant Patient with Hypoalbuminemia

2000 ◽  
Vol 34 (2) ◽  
pp. 183-187 ◽  
Author(s):  
Jeffrey A Haroldson ◽  
Linda E Kramer ◽  
Denise L Wolff ◽  
Kathleen D Lake
Keyword(s):  
Valproic Acid ◽  
Adverse Effects ◽  
Serum Concentration ◽  
Transplant Patient ◽  
Total Serum ◽  
Heart Transplant Patient ◽  
Serum Concentrations ◽  
Case Summary ◽  
Related Adverse Effect ◽  
Drug Concentrations

OBJECTIVE: To report a case demonstrating the importance of monitoring unbound valproic acid (VPA) serum concentrations in a patient with hypoalbuminemia. CASE SUMMARY: A 53-year-old white woman status–post heart transplantation was admitted to the hospital for declining cardiac function, possible rejection, and increased lethargy requiring intubation. An extensive workup of the patient's profound lethargy was initiated, including an evaluation of her VPA regimen. Initially, VPA dosages were adjusted based on the total serum concentration of VPA. Hypoalbuminemia compounded with increased lethargy prompted the measurement of unbound serum concentrations of VPA. The VPA dosage was then adjusted based on the unbound rather than the total VPA serum concentration; the patient eventually improved and was discharged from the hospital. DISCUSSION: Lethargy is a concentration-related adverse effect of VPA. The nonlinear pharmacokinetic and protein saturation characteristics of VPA may result in nonproportional elevations in unbound drug, and subsequent increases in adverse effects, when dosage adjustments are based solely on measurement of total VPA serum concentrations in patients with hypoalbuminemia. CONCLUSIONS: This case report suggests that appropriate monitoring of unbound drug concentrations of VPA may prevent unrecognized concentration-related adverse effects. Awareness of the pharmacokinetic relationship and adverse effects of VPA will aid clinicians in identifying the etiology of symptoms.

scholarly journals The Effect of ARHGEF15 Knockout and Forebrain-Specific Human ARHGEF15 Knock-In on Seizure Susceptibility in Mice

2021 ◽  
Author(s):  
Yi-Dan Liu ◽  
Meng-Yu Ma ◽  
Yan-Ling Wang ◽  
Mei-Juan Ding ◽  
Yu Yang ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Total Duration ◽  
Epileptic Seizures ◽  
Clonic Seizure ◽  
Tonic Clonic Seizure ◽  
Nucleotide Exchange ◽  
Adult Mice ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Significant Difference

Abstract Background The ARHGEF15 gene encodes the Rho guanine nucleotide exchange factor 15. Although multiple evidence indicates that ARHGEF15 may be related to epilepsy, it is not clear what role it plays. Methods Subjects were homozygous ARHGEF15 knockout (E5−/−) mice, wild-type (WT) mice, Cre-positive homozygous human ARHGEF15 conditional knock-in (E5CKI/CKI•Cre+) mice which can overexpress human Ephexin5 in the forebrain, and Cre-positive (E5WT/WT•Cre+) mice. Models with epileptic seizures were established by intraperitoneal injection of pentylenetetrazol (PTZ) in 60 mg/kg, and seizures were recorded by video. Then 7 indexes were counted, including “maximum seizure level”, “seizure level classification”, “tonic-clonic seizure or not”, “latency of tonic-clonic seizure”, “number of times of tonic-clonic seizure”, “total duration of tonic-clonic seizure”, and “dead or not”. Western blot was used to detect Ephexin5, RhoA, p-RhoA, ROCK2, and p-ROCK2 in WT mice and E5−/− mice. Results Compared with WT mice, E5−/− mice had a shorter “total duration of tonic-clonic seizure”. For levels of RhoA, p-RhoA, ROCK2 and p-ROCK2 in the adult hippocampus, there was no significant difference between WT and E5−/−. The level of Ephexin5 was high in the whole brain tissue of 2-day-old WT mice, and an extremely low expression of Ephexin5 was detected in the brain tissue of E5−/− mice of the same age. There was no significant difference between E5CKI/CKI•Cre + mice and E5WT/WT•Cre + mice in seizures. Conclusions ARHGEF15 knockout can decrease the “duration of tonic-clonic seizure” in adult mice with epileptic seizures induced by PTZ. ARHGEF15 knockout did not affect the expression of the RhoA-ROCK2 pathway in the hippocampus of adult mice, which probably attributed to no expression of Ephexin5 in the hippocampus of adult mice. The overexpression of human Ephexin5 in the forebrain has no significant effect on the behavior of epileptic seizures induced by PTZ in adult mice.

scholarly journals Gray matter heterotopia: clinical and neuroimaging report on 22 children

2021 ◽  
Author(s):  
A. Di Nora ◽  
G. Costanza ◽  
F. Pizzo ◽  
C. F. Oliva ◽  
A. Di Mari ◽  
...  
Keyword(s):  
Gray Matter ◽  
Clinical Characteristics ◽  
Epileptic Seizures ◽  
Clonic Seizure ◽  
Clinical Findings ◽  
Magnetic Resonance Images ◽  
Tonic Clonic Seizure ◽  
Subcortical Band Heterotopia ◽  
Periventricular Heterotopia ◽  
Intellectual Deficit

Abstract Objective To investigate the clinical characteristics and neuroimaging features of childhood presenting with gray matter heterotopia observed in a single tertiary Pediatric Department in Catania and compare the data with those reported in the literature. Methods A retrospectively review of the history, clinical findings, electrophysiological features and magnetic resonance images of 22 children presenting with gray matter heterotopia observed from January 2010 to January 2020. Results Among the 22 children included in the study, 17 presented with periventricular heterotopia (PVNH), two with Subcortical Band Heterotopia (SBH), and three with other subcortical heterotopia (SUBH). In the affected children, the ages at first diagnosis ranged from 3 months to 16 years with a mean age of 8.2 years (± 5.4); twelve (54.5%) suffered by developmental delay and intellectual deficit; eleven children (50%) complained of epileptic seizures, mostly focal to bilateral tonic–clonic seizure. In addition, in the periventricular heterotopia group (PVNH), cerebral and systemic malformations were reported in twelve (70%) and in ten (58%) children, respectively, out of seventeen. In the SBH plus SUBH group, epileptic seizures were recorded in 3 (60%) out of 5 children, cerebral malformations in one child and systemic malformations in two children. Conclusions Heterotopic gray matter malformations include a group of disorders that manifest with a variety of neurological implications, such as cognitive impairment and epilepsy, and often related with epilepsy, other cerebral malformations and systemic anomalies.

scholarly journals Seizure following the Use of the COX-2 Inhibitor Etoricoxib

2017 ◽  
Vol 2017 ◽  
pp. 1-3
Author(s):  
Valentina Arnao ◽  
Marianna Riolo ◽  
Brigida Fierro ◽  
Paolo Aridon
Keyword(s):  
Clinical Presentation ◽  
Clinical Symptoms ◽  
Epileptic Seizures ◽  
Clonic Seizure ◽  
Tonic Clonic Seizure ◽  
Generalized Seizures ◽  
Appropriate Treatment ◽  
History Of ◽  
Cox 2 ◽  
Cox 2 Inhibitors

We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this. Conclusion. Knowing the pharmacological history of a patient is important for understanding the clinical presentation and selecting appropriate treatment. This is, to the best of our knowledge, the first reported case of generalized seizures associated with the use of COX-2 inhibitors.

scholarly journals Valproic Acid Concentrations in Mothers, Colostrum and Breastfed Infants during the Early Postpartum Period: Comparison with Concentrations Determined during Delivery and in the Mature Milk Period

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2074
Author(s):  
Ivana Kacirova ◽  
Milan Grundmann ◽  
Hana Brozmanova
Keyword(s):  
Valproic Acid ◽  
Serum Concentration ◽  
Lower Limit ◽  
Concentration Ratio ◽  
Maternal Serum ◽  
Serum Concentrations ◽  
Limit Of Quantification ◽  
Mature Milk ◽  
Breastfed Infants ◽  
Routine Monitoring

To obtain information on the transport of valproic acid from mothers to colostrum and breastfed infants, in this cohort study, valproic acid concentrations in maternal serum (90 subjects), colostrum and the serum of breastfed infants were analyzed in years 1993–2018, between the 2nd and 5th postnatal days. Valproic acid concentrations ranged from 4.3 to 66.5 mg/L (mean 31.2 ± 13.6 mg/L) in maternal serum, from 0.5 to 5.9 mg/L (mean 1.1 ± 1.2 mg/L) in milk, and from 0.5 to 42.9 mg/L (mean 15.4 ± 9.4 mg/L) in infant serum. The milk/maternal serum concentration ratio ranged from 0.01 to 0.22 (mean 0.04 ± 0.04), and the infant/maternal serum concentration ratio ranged from 0.01 to 1.61 (mean 0.51 ± 0.28). A significant correlation was found between serum concentrations of breastfed infants and milk concentrations, maternal serum concentrations, maternal daily dose, and dose related to maternal body weight. Valproic acid concentrations in milk and infant serum did not reach the lower limit of the reference range used for the general epileptic population, and three-quarters of the concentrations in milk were lower than the lower limit of quantification. Routine monitoring of serum concentrations of breastfed infants is not necessary. If signs of potential adverse reactions are noted, serum concentrations of the infants should be measured.

Valproic Acid–Induced Neutropenia

2003 ◽  
Vol 37 (6) ◽  
pp. 819-821 ◽  
Author(s):  
Kimi S Vesta ◽  
Patrick J Medina
Keyword(s):  
Valproic Acid ◽  
White Woman ◽  
Seizure Activity ◽  
Clonic Seizure ◽  
Tonic Clonic Seizure ◽  
Severe Neutropenia ◽  
Probability Scale ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
Case Summary

OBJECTIVE: To report a case of severe neutropenia caused by valproic acid (VPA). CASE SUMMARY: A 56-year-old white woman with an infectious brain abscess causing tonic–clonic seizure activity was treated with VPA. She developed severe neutropenia after 2 days of VPA therapy. The absolute neutrophil count reached a nadir of 47 cells/mm3 during VPA use and returned to normal upon its discontinuation. DISCUSSION: VPA is considered to be a well-tolerated antiepileptic drug. While neutropenia has been reported, it has been mild and transient. This patient developed severe neutropenia during effective treatment with VPA, making her significantly susceptible to infection. The Naranjo probability scale indicates VPA as the probable cause of neutropenia in this case. CONCLUSIONS: This report of severe neutropenia caused by VPA emphasizes the importance of monitoring complete blood cell counts during therapy with this agent.

scholarly journals Valproate serum concentrations in patients with hypoalbuminemia and medical complications

2017 ◽  
Vol 7 (1) ◽  
pp. 13-15
Author(s):  
Amy VandenBerg ◽  
Jessica Broadway ◽  
Callie Lalich ◽  
Rachel Kennedy ◽  
Kristen Williams
Keyword(s):  
Valproic Acid ◽  
Serum Concentration ◽  
Free Fraction ◽  
Serum Concentrations ◽  
Model Free ◽  
Acid Protein ◽  
Patients Experience ◽  
Patients With Epilepsy ◽  
Key Terms ◽  
Free Serum

Abstract Introduction: Valproic acid (VPA) and its derivatives are highly protein bound with free fraction increasing with dose and serum concentration. Consensus guidelines regarding dose adjustment for hypoalbuminemia are not available. Methods: A literature search was performed using PubMed to identify articles with the following key terms: “valproate,” “valproic acid,” “protein binding,” “albumin,” and “hypoalbuminemia.” We report our findings as well as 5 cases involving pharmacokinetic impact of hypoalbuminemia on valproate. Results: A previously published model for normalizing VPA serum concentration for hypoalbuminemia in patients with epilepsy was compared to results for 5 cases (4 female, 1 male) in which VPA was used for psychiatric illness. Only 1 of the cases had free serum concentrations in the range that would be expected with the model. Free concentrations ranged from 22% to 83% with no clear relationship to other factors (weight, age, serum creatinine, or dose). Female patients with similar albumin had higher free fractions than the 1 male patient. Discussion: Due to the variability in pharmacokinetic impact of hypoalbuminemia, it is important to monitor patients closely for signs of VPA toxicity in cases involving altered albumin levels. It would be prudent to use free serum VPA concentrations when patients experience fluctuations in albumin or have unexpected response to medication.

Serum Concentration and Skin Expression of S100A7 (Psoriasin) in Patients Suffering from Hidradenitis Suppurativa

Dermatology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Aleksandra Batycka-Baran ◽  
Wojciech Baran ◽  
Danuta Nowicka-Suszko ◽  
Maria Koziol-Gałczyńska ◽  
Andrzej Bieniek ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Hidradenitis Suppurativa ◽  
Protein Concentration ◽  
Normal Skin ◽  
Innate Immune ◽  
Antimicrobial Protein ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Reactive Protein

<b><i>Background:</i></b> Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. An important role of innate immune dysregulation in the pathogenesis of HS has been highlighted. S100A7 (psoriasin) is an innate, antimicrobial protein that exerts proinflammatory and chemotactic action. <b><i>Objectives:</i></b> The objective of the study was to investigate serum concentrations of S100A7 in individuals with HS as compared to healthy controls. Further, we evaluated the expression of S100A7 in lesional HS skin as compared to perilesional (clinically uninvolved) HS skin and normal skin. <b><i>Methods:</i></b> Serum concentrations of S100A7 were evaluated with a commercially available ELISA kit. The expression of S100A7 in the skin was assessed using qRT-PCR and immunofluorescence staining. <b><i>Results:</i></b> We found increased expression of S100A7 in lesional HS skin as compared to perilesional HS skin (<i>p</i> = 0.0017). The expression of S100A7 in lesional HS skin was positively associated with serum C-reactive protein concentration and the severity of disease according to Hurley staging. The serum concentration of S100A7 in individuals with HS was decreased as compared to healthy controls and patients with psoriasis. <b><i>Conclusions:</i></b> Upregulated in lesional HS skin, S100A7 may enhance the inflammatory process and contribute to the HS pathogenesis.

scholarly journals Dynamic structural neuroplasticity during and after epileptogenesis in a pilocarpine rat model of epilepsy

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Soomaayeh Heysieattalab ◽  
Leila Sadeghi
Keyword(s):  
Rat Model ◽  
Chronic Phase ◽  
Structural Plasticity ◽  
Epileptic Seizures ◽  
Experimental Models ◽  
Spontaneous Seizures ◽  
Maladaptive Plasticity ◽  
Male Wistar Rats ◽  
Spontaneous Recurrent Seizures ◽  
Latent Phase

Abstract Background The role of neuroplasticity in epilepsy has been widely studied in experimental models and human brain samples. However, the results are contradictory and it remains unclear if neuroplasticity is more related to the cause or the consequence of epileptic seizures. Clarifying this issue can provide insights into epilepsy therapies that target the disease mechanism and etiology rather than symptoms. Therefore, this study was aimed to investigate the dynamic changes of structural plasticity in a pilocarpine rat model of epilepsy. Methods A single acute dose of pilocarpine (380 mg/kg, i.p.) was injected into adult male Wistar rats to induce status epilepticus (SE). Animal behavior was monitored for 2 h. Immunohistochemical staining was performed to evaluate neurogenesis in the CA3 and dentate gyrus (DG) regions of hippocampus using biomarkers Ki67 and doublecortin (DCX). The Golgi-Cox method was performed to analyze dendritic length and complexity. All experiments were performed in control rats (baseline), at 24 h after SE, on day 20 after SE (latent phase), after the first and 10th spontaneous recurrent seizures (SRS; chronic phase), and in non-epileptic rats (which did not manifest SRS 36 days after pilocarpine injection). Results SE significantly increased the number of Ki67 and DCX-positive cells, suggesting neurogenesis during the latent phase. The dendritic complexity monitoring showed that plasticity was altered differently during epilepsy and epileptogenesis, suggesting that the two processes are completely separate at molecular and physiological levels. The numbers of spines and mushroom-type spines were increased in the latent phase. However, the dendritogenesis and spine numbers did not increase in rats that were unable to manifest spontaneous seizures after SE. Conclusion All parameters of structural plasticity that increase during epileptogenesis, are reduced by spontaneous seizure occurrence, which suggests that the development of epilepsy involves maladaptive plastic changes. Therefore, the maladaptive plasticity biomarkers can be used to predict epilepsy before development of SRS in the cases of serious brain injury.

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