Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both estrogen and progesterone influence seizure activity in women with epilepsy, with estrogen generally demonstrating proconvulsant and progesterone anticonvulsant effects. Women with epilepsy exhibit a variety of endocrine disturbances, probably due to a combination of factors, including the epilepsy syndrome and the effect of interictal and ictal epileptic discharges in the brain. The direct effects of some antiepileptic drugs (AEDs) further increase this risk, apparently related to a specific drug's effect on hepatic microsomal enzymes of the cytochrome P-450 system. AEDs that induce hepatic microsomal enzymes also interact with hormonal contraception to increase estrogen's metabolism and progesterone's protein binding, decreasing concentrations of both hormones and thus reducing contraceptive efficacy. Some evidence indicates that concurrent use of hormonal contraceptives and lamotrigine significantly decreases the plasma concentration of lamotrigine, suggesting that close monitoring is warranted. Nevertheless, hormonal contraception confers comparable or superior efficacy compared with such other contraceptives as the intrauterine device and barrier methods and remains an appropriate option in women with epilepsy. Importantly, concurrent use of hormonal contraception and AEDs does not adversely affect seizure control. Careful patient management, including the use of increased estrogen doses (> or =50 microg) in patients receiving enzyme-inducing AEDs, may further minimize the risk for unintended pregnancy. Special considerations in women of childbearing age include decreased compliance and disease prevention. Although adequate seizure control is the critical requirement of an AED, the potential for interactions with hormonal contraception and the increased risk for endocrine disturbances caused by drugs that alter hepatic microsomal enzymes suggest additional potential advantages for AED treatment that does not affect these enzymes. Both the constellation of physicians treating women with epilepsy and the patients themselves have a poor understanding of the spectrum of reproductive health issues involved, and increased awareness is needed to improve patient management.
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PMID:Antiepileptic drugs and hormonal contraceptives in adolescent women with epilepsy. 1656 41

Seizures commonly occur in people with brain tumors. They may be the presenting symptom of a brain tumor, or develop some time after tumor diagnosis. The risk of seizures is greatest when the tumors have a central location, slow growth rate, and when multiple lesions are present. Interactions between anti-epileptic drugs (AEDs), chemotherapeutic agents, and corticosteroids increase the complexity and challenge in managing seizures, and drugs that do not interfere with the cytochrome P-450 enzyme complex and have low protein binding may be preferable. The comparative efficacy and side effects of the various AEDs are not established in brain tumors, so drug choice relies on both the theoretical advantages of pharmacokinetic properties and clinical judgment. Prophylactic anticonvulsant treatment is not advisable in brain tumor patients who have not experienced seizures.
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PMID:Seizures and brain tumors. 1676 22

Both seizures and antiepileptic drugs may induce disturbances in hormonal system. Regarding endocrine effects of anticonvulsants, an interaction of these drugs with gonadal, thyroid, and adrenal axis deserves attention. Since majority of antiepileptic drugs block voltage dependent sodium and calcium channels, enhance GABAergic transmission and/or antagonize glutamate receptors, one may expect that similar neurochemical mechanisms are engaged in the interaction of these drugs with synthesis of hypothalamic neurohormones such as gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH) and growth hormone releasing hormone (GHRH). Moreover some antiepileptic drugs may affect hormone metabolism via inhibiting or stimulating cytochrome P-450 iso-enzymes. An influence of antiepileptic drugs on hypothalamic-pituitary-gonadal axis appears to be sex-dependent. In males, valproate decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but elevated dehydroepiandrosterone sulfate (DHEAS) concentrations. Carbamazepine decreased testosterone/sex-hormone binding globulin (SHBG) ratio, whereas its active metabolite--oxcarbazepine--had no effect on androgens. In females, valproate decreased FSH-stimulated estradiol release and enhanced testosterone level. On the other hand, carbamazepine decreased testosterone level but enhanced SHBG concentration. It has been reported that carbamazepine, oxcarbazepine or joined administration of carbamazepine and valproate decrease thyroxine (T4) level in patients with no effect on thyrotropin (TSH). While valproate itself has no effect on T4, phenytoin, phenobarbital and primidone, as metabolic enzyme inducers, can decrease the level of free and bound thyroxine. On the other hand, new antiepileptics such as levetiracetam, tiagabine, vigabatrine or lamotrigine had no effect on thyroid hormones. With respect to hormonal regulation of metabolic processes, valproate was reported to enhance leptin and insulin blood level and increased body weight, whereas topiramate showed an opposite effect. In contrast to thyroid and gonadal hormones, only a few data concern antiepileptic drug action in HPA axis. To this end, no effect of antiepileptic drugs on adrenocorticotropic hormone (ACTH)/cortisol circadian rhytmicity was found. Valproate decreased CRH release in rats, whereas lamotrigine stabilized ACTH/cortisol secretion. Moreover, felbamate was found to inhibit stress-induced corticosterone release in mice. Interestingly, recent data suggest that felbamat and some other new antiepileptic drugs may inhibit transcriptional activity of glucocorticoid receptors. Summing up, the above data suggest that traditional antiepileptic drugs may cause endocrine disturbances, especially in gonadal hormones.
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PMID:[Endocrine effects of antiepileptic drugs]. 1920 63

PURPOSE The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, and place in therapy of dalfampridine are reviewed. SUMMARY Dalfampridine is a novel drug with a unique mechanism for the symptomatic management of multiple sclerosis (MS) among all classifications. Dalfampridine was approved in January 2010 to improve walking for patients with MS. Dalfampridine blocks potassium channels on demyelinated neurons and allows normal electrical conduction, thus improving locomotor difficulty. Dalfampridine is rapidly absorbed after oral administration, reaching its peak plasma concentration in 1.3 hours. Approximately 95.9% of dalfampridine and its metabolites (3-hydroxy-4-aminopyridine and 3- hydroxy-4-aminopyridine sulfate) is excreted in the urine. Dalfampridine is not an inhibitor or inducer of a major cytochrome P-450 isoenzyme; therefore, the potential for drug-drug interactions is minimal. Clinical studies have shown dalfampridine to improve walking speed. The dosage of dalfampridine varied in clinical trials, but the recommended dosage is 10 mg orally twice daily. Dalfampridine is not appropriate for patients with seizures or moderate-to-severe renal impairment. Phase III studies found that extended-release fampridine 10 mg twice daily is well tolerated. The most frequent adverse events reported in dalfampridine clinical trials were insomnia, dizziness, headache, nausea, and weakness. The Food and Drug Administration has required the manufacturer to have a risk evaluation and mitigation strategy for dalfampridine. Ongoing trials will determine the long-term benefit of dalfampridine. CONCLUSION Dalfampridine is a potassium channel blocker that has demonstrated efficacy for improving the symptoms of MS. Several studies have demonstrated increased walking speed in patients, though high doses should be avoided due to the risk of seizures.
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PMID:Dalfampridine: a new agent for symptomatic management of multiple sclerosis. 2213 60

Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug-drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures in those with idiopathic generalized epilepsy.
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PMID:Development of lacosamide for the treatment of partial-onset seizures. 2385 1

Tramadol is commonly prescribed for pain control because it presents a lower risk for addiction and respiratory depression compared to other opioids. However, tramadol's serotonin and norepinephrine reuptake inhibitory effects result in a unique adverse effect profile. Two such adverse events are serotonin syndrome and seizures. The prevalence of tramadol-induced serotonin syndrome and seizures is modest in the general population, but if left untreated, the morbidity and mortality can be high; therefore, prompt recognition and management is essential. Various risk factors such as medical comorbidities, use or abuse of supratherapeutic doses of tramadol, and concomitant administration of proconvulsant serotonergic cytochrome P-450 inhibitors will help clinicians identify individuals at an elevated risk for serotonin toxicity and seizures. Serotonin syndrome and seizures can be effectively treated by administering benzodiazepines, providing supportive care, and discontinuing tramadol and other contributing agents. Cyproheptadine should be administered in moderate to severe cases of serotonin syndrome. Our objective is to summarize the literature on the pharmacology, epidemiology, risk factors, clinical presentations, and evidence-based management of tramadol-related seizures and serotonin syndrome.
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PMID:Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures. 3039 47


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