Epilepsia
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Among some 14 new antiepileptic drugs (AEDs), those most extensively tested in humans include felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), vigabatrin (VGB), and zonisamide (ZNS). All are currently marketed in some but not all countries. Although no large, comparative studies on efficacy have been conducted, all of these new AEDs are effective in adult localization-related epilepsies, and some have activity in specific syndromes. ⋯ Half-life of ZNS is 27-36 h. ZNS daily dosage is 400-600 mg. ZNS has been effective in some cases of Baltic myoclonic epilepsy.
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Review
Emerging insights into mechanisms of epilepsy: implications for new antiepileptic drug development.
Most currently available antiepileptic drugs (AEDs) were developed by testing new compounds in animal models of seizures. Increased knowledge of the cellular and molecular mechanisms underlying normal CNS function and seizure phenomena is now being used to design new AEDs specifically to interfere with epileptic mechanisms. Focal epilepsy develops in areas of cortex that are damaged and in which aberrant recurrent excitatory circuits develop, producing spike discharges in the EEG. ⋯ They also appear to be involved in some forms of primary generalized epilepsy, in which burst discharges due to calcium currents in deep diencephalic neurons with widely ramifying axons may act as synchronizing influences. Neuromodulatory agents, including purines, peptides, cytokines, and steroid hormones, also play important roles in regulating brain excitability. Adenosine in some experimental models act as an endogenous antiepileptic substance, and agents that enhance the actions of adenosine are often antiepileptic in animal models.(ABSTRACT TRUNCATED AT 250 WORDS)
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Vigabatrin, lamotrigine, and oxcarbazepine are three of the many new antiepileptic drugs (AEDs) already registered in several countries that highlight some of the typical problems and prejudices of new AEDs. Both the therapeutic action and the side-effect profiles of new AEDs are only basically known with marketing. ⋯ All three have some effect on focal seizures, but their clinical spectrum probably will turn out to be by no means uniform. These three AEDs are, in general, well tolerated, but it would be premature to compare their safety with traditional AEDs as one must be prepared for rare or delayed untoward effects that may be discovered later, as occurred with some older AEDs.
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Review of randomized controlled trials (RCTs) shows that valproate (VPA) is effective against partial seizures with or without becoming secondarily generalized. A number of RCTs show little difference in the efficacy of VPA and carbamazepine in this patient group, particularly where patients are randomized at the time of diagnosis. The length of time that it has taken to arrive at these conclusions emphasizes the importance of large active-controlled RCTs at an early stage in drug development in informing clinical practice.
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Propofol is a new, fast-acting intravenous (i.v.) anesthetic. Involuntary movements or epileptic seizures have occurred during or after propofol-induced anesthesia in approximately 50 reported cases; a third of the patients have had epilepsy. ⋯ A female epileptic patient developed severe status epilepticus; the other patients with short-lasting seizures had no previous epilepsy. Although propofol has been used in treatment of patients of status epilepticus, the risk of precipitation of epileptic seizures warrants consideration especially when planning anesthesia for epileptic patients.