scholarly journals Cardiac Sodium Channel Blockade Due to Antiepileptic Drug Combination

2021 ◽  
Author(s):  
Ossama Maadarani ◽  
Zouheir Bitar ◽  
Abdelaziz Ashkanani ◽  
Mahmoud Elzoueiry ◽  
Mohamad Elhabibi ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Adjunctive Treatment ◽  
Channel Blockers ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
First Choice ◽  
Cardiac Sodium Channel ◽  
Voltage Dependent ◽  
Long Time ◽  
The Usa

Drugs that inhibit voltage-dependent sodium channels are commonly used to treat epilepsy. Old and novel antiepileptic drugs are used either as monotherapy or in combination to control epilepsy. For a long time, carbamazepine has been used as the first choice for the treatment of simple and complex partial seizures. In the USA, lacosamide was approved in October 2008 as an adjunctive treatment for partial-onset seizures. We describe the effect of two sodium channel blockers on the heart of a patient with epilepsy.

Rat to human translation of effects of cardiac sodium channel blockers

2010 ◽  
Vol 62 (2) ◽  
pp. e43
Author(s):  
Stella P. Worton ◽  
Bethan K. Lawton ◽  
Chris P. Doe ◽  
Nick McMahon
Keyword(s):  
Sodium Channel ◽  
Channel Blockers ◽  
Sodium Channel Blockers ◽  
Cardiac Sodium Channel

Potassium currents in rat cortical neurons in culture are enhanced by the antiepileptic drug carbamazepine

1990 ◽  
Vol 68 (4) ◽  
pp. 545-547 ◽  
Author(s):  
C. Zona ◽  
V. Tancredi ◽  
E. Palma ◽  
G. C. Pirrone ◽  
M. Avoli
Keyword(s):  
Antiepileptic Drug ◽  
Antiepileptic Drugs ◽  
Cortical Neurons ◽  
Potassium Currents ◽  
Patch Clamping ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
Voltage Dependent ◽  
Rat Neocortex ◽  
Rat Cortical Neurons

We report that carbamazepine (Tegretol), a drug that is useful for the treatment of complex partial seizures, enhances outward, voltage-dependent K+ currents generated by rat neocortical cells in culture and recorded with patch-clamping techniques. This effect is seen in the presence of therapeutic concentrations of carbamazepine (10–20 μM). Furthermore, at these doses carbamazepine does not influence voltage-dependent inward Na+ and Ca2+ currents recorded in these cells. The action exerted by carbamazepine on K+ currents is a novel finding and might represent an important mechanism for controlling neocortical excitability and thus the generation of epileptiform activity.Key words: potassium currents, antiepileptic drugs, carbamazepine, rat neocortex.

Vigabatrin in Refractory Complex Partial Seizures: The Evidence of its Therapeutic Value

2010 ◽  
Vol 2 ◽  
pp. CMT.S3788
Author(s):  
Michele A. Faulkner ◽  
Justin A. Tolman
Keyword(s):  
Vision Loss ◽  
Peripheral Vision ◽  
The United States ◽  
Adjunctive Treatment ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
Psychiatric Disturbances ◽  
Therapeutic Value ◽  
Number Of Patients ◽  
Unites States

Vigabatrin (Sabril®) has recently been granted approval in the Unites States for the adjunctive treatment of complex-partial seizures in adults. The drug was first evaluated as a potential therapy for this population decades ago, and it has been available in other parts of the world for some time. Well controlled studies demonstrate that at doses up to 3 g/day, the drug is efficacious as add-on therapy for treatment resistant seizures. However, vigabatrin has been associated with significant side-effects limiting its use, and relegating it to a late therapeutic alternative. Specifically, vigabatrin has been implicated in the development of irreversible peripheral vision loss in a significant number of patients. For this reason, the approval of the drug in the United States was contingent upon the introduction of a rigorous monitoring protocol that must accompany its use. Additionally, the drug has been associated with a relatively high incidence of psychiatric disturbances, although there is disagreement about a direct correlation of these symptoms to the drug. Still, the drug remains a viable alternative for patients who have failed therapy with traditional anti-seizure medications.

Voltage-dependent sodium channel blocker anticonvulsants: an approach to the structure-activity relationship

2020 ◽  
Vol 16 ◽  
Author(s):  
M. del Carmen Salazar-López ◽  
J. Alberto Guevara-Salazar ◽  
Mónica G. Arellano-Mendoza ◽  
Hugo A. Jiménez-Vázquez ◽  
Adriana Benavides ◽  
...  
Keyword(s):  
Biological Activity ◽  
Sodium Channel ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Channel Blockers ◽  
Experimental Conditions ◽  
Electronic Density ◽  
Relationship Analysis ◽  
Structure Activity ◽  
Voltage Dependent

: Anticonvulsants are drugs used in the treatment of seizures, their pharmacology includes promoters of brain inhibition and inhibitors of brain activity; Of the latter, voltage-dependent sodium channel blockers (VGSCB) are the most widely used in therapeutics. Objective: To propose the structural requirements of VGSC blockers through a quantitative structure-activity relationship analysis of drugs with proven activity. Methods: IC50 values of anticonvulsant drugs on VGSCs were considered under similar experimental conditions; some physicochemical properties of the molecules that were correlated with their biological activity were determined in silico. Results: Relationships were found between the dipole moment, pKa, EHOMO, and MR with the biological activity, which infers that between greater polarity and basicity of the drugs, their activity as blockers will increase. Subsequently, the structural subclassification of the drugs was carried out, based on the urea derivation, the groups of which were: Group 1 (direct and bioisoster derivatives) and Group 2 (homologue and vinylogue derivatives of urea). Conclusion: The biological activity depends on the polarity, basicity, and electronic density of the drugs. The derivation of urea is essential, which is present in its original substituted form or a bioisosteric form. Urea can be in the form of a homologue or a vinylogue at the ends of the molecule. Aromatic substitution to the urea portion is necessary.

scholarly journals Novel charged sodium and calcium channel inhibitor active against neurogenic inflammation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Seungkyu Lee ◽  
Sooyeon Jo ◽  
Sébastien Talbot ◽  
Han-Xiong Bear Zhang ◽  
Masakazu Kotoda ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Sodium Channel ◽  
Dorsal Root Ganglion Neurons ◽  
Channel Blockers ◽  
Potent Inhibition ◽  
Calcitonin Gene ◽  
Peptide Release ◽  
Voltage Dependent ◽  
Ganglion Neurons

Voltage-dependent sodium and calcium channels in pain-initiating nociceptor neurons are attractive targets for new analgesics. We made a permanently charged cationic derivative of an N-type calcium channel-inhibitor. Unlike cationic derivatives of local anesthetic sodium channel blockers like QX-314, this cationic compound inhibited N-type calcium channels more effectively with extracellular than intracellular application. Surprisingly, the compound is also a highly effective sodium channel inhibitor when applied extracellularly, producing more potent inhibition than lidocaine or bupivacaine. The charged inhibitor produced potent and long-lasting analgesia in mouse models of incisional wound and inflammatory pain, inhibited release of the neuropeptide calcitonin gene-related peptide (CGRP) from dorsal root ganglion neurons, and reduced inflammation in a mouse model of allergic asthma, which has a strong neurogenic component. The results show that some cationic molecules applied extracellularly can powerfully inhibit both sodium channels and calcium channels, thereby blocking both nociceptor excitability and pro-inflammatory peptide release.

scholarly journals A rare case of Brugada syndrome induced by hyperglycemia

2021 ◽  
Vol 8 (2) ◽  
pp. 25-30
Author(s):  
Brandon Knopp ◽  
Bailey Pierce ◽  
Vishnu Muppala
Keyword(s):  
Cardiac Arrest ◽  
Sodium Channel ◽  
Brugada Syndrome ◽  
Genetic Disorder ◽  
Diabetic Patients ◽  
Channel Blockers ◽  
Increased Risk ◽  
Cardiac Sodium Channel ◽  
Cardiac Sodium Channels ◽  
Brugada Pattern

Brugada syndrome is a rare genetic disorder of the cardiac sodium channels associated with an increased risk of sudden cardiac death. It is characterized by an electrocardiogram (EKG) showing a right bundle branch block with an elevation in the ST segment. This condition is associated with mutations in several pathologic genes including the most notable mutation in the SCN5A gene, which encodes for a voltage-gated cardiac sodium channel. The Brugada pattern on EKG can be spontaneous but can also be induced by a variety of etiologies including fever, electrolyte abnormalities, increased vagal tone and drugs such as sodium channel blockers, calcium channel blockers, tricyclic antidepressants and alcohol. One uncommon cause of Brugada syndrome is hyperglycemia. Of particular importance in diabetic patients, hyperglycemia can induce chronic cardiovascular complications as well as acute cardiac events via the induction of the Brugada pattern on EKG. We present a case of a 21-year-old non-insulin compliant diabetic man presenting to the Emergency Department with diabetic ketoacidosis (DKA) who exhibits the Brugada pattern EKG prior to developing ventricular tachycardia followed by cardiac arrest. The patient’s condition was induced by prolonged hyperglycemia in the setting of DKA with relatively mild electrolyte and pH abnormalities. Herein, this case is presented to highlight the Brugada pattern leading to cardiac arrest as a potential consequence of hyperglycemia and inform physicians on its incidence.

Time Interval Between Traumatic Brain Injury And Post Traumatic Epilepsy

2013 ◽  
Vol 21 (2) ◽  
pp. 222-228
Author(s):  
Daniel Garbin Di Luca ◽  
Glenda Corrêa Borges de Lacerda
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
First Year ◽  
Time Interval ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
Post Traumatic ◽  
Faster Development ◽  
Post Traumatic Epilepsy ◽  
Traumatic Epilepsy

Introduction. The estimated time interval in which an individual can develop Post Traumatic Epilepsy (PTE) after a traumatic brain injury (TBI) is not clear. Objective. To assess the possible influence of the clinical features in the time interval between TBI and PTE develop­ment. Method. We analyzed retrospectively 400 medical records from a tertiary Brazilian hospital. We selected and reevaluated 50 patients and data was confronted with the time between TBI and PTE devel­opment by a Kaplan-Meier survival analysis. A Cox-hazard regression was also conducted to define the characteristics that could be involved in the latent period of the PTE development. Results. Patients devel­oped PTE especially in the first year (56%). We found a tendency of a faster development of PTE in patients older than 24 years (P<0.0001) and in men (P=0.03). Complex partial seizures evolving to generalized seizures were predominant in patients after moderate (37.7%) and severe (48.8%) TBIs, and simple partial seizures evolving to general­ized seizures in mild TBIs (45.5%). Conclusions. Our data suggest that the first year after a TBI is the most critical period for PTE de­velopment and those males older than 24 years could have a faster development of PTE.

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