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Jai Ganesh

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Registered: 2005-06-28

Posts: 46,267

Anticonvulsants

Anticonvulsants

Gist

Anticonvulsants, or antiepileptics, are an ever-growing class of medications that act through multiple different mechanisms to control seizures — antiepileptic toxicity commonly presents with a triad of symptoms, which includes central nervous system (CNS) depression, ataxia, and nystagmus.

Details

Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, and anti-seizure medications [ASM]) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.

Conventional antiepileptic drugs may block sodium channels or enhance γ-aminobutyric acid (GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action. Next to the voltage-gated sodium channels and components of the GABA system, their targets include GABAA receptors, the GAT-1 GABA transporter, and GABA transaminase. Additional targets include voltage-gated calcium channels, SV2A, and α2δ. By blocking sodium or calcium channels, antiepileptic drugs reduce the release of excitatory glutamate, whose release is considered to be elevated in epilepsy, but also that of GABA. This is probably a side effect or even the actual mechanism of action for some antiepileptic drugs, since GABA can itself, directly or indirectly, act proconvulsively. Another potential target of antiepileptic drugs is the peroxisome proliferator-activated receptor alpha.

Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy. That is, they either prevent the development of epilepsy or can halt or reverse the progression of epilepsy. However, no drug has been shown in human trials to prevent epileptogenesis (the development of epilepsy in an individual at risk, such as after a head injury).

Terminology

Anticonvulsants are more accurately called antiepileptic drugs (abbreviated "AEDs"), and are often referred to as antiseizure drugs because they provide symptomatic treatment only and have not been demonstrated to alter the course of epilepsy.

Approval

The usual method of achieving approval for a drug is to show it is effective when compared against placebo, or that it is more effective than an existing drug. In monotherapy (where only one drug is taken) it is considered unethical by most to conduct a trial with placebo on a new drug of uncertain efficacy. This is because untreated epilepsy leaves the patient at significant risk of death. Therefore, almost all new epilepsy drugs are initially approved only as adjunctive (add-on) therapies. Patients whose epilepsy is uncontrolled by their medication (i.e., it is refractory to treatment) are selected to see if supplementing the medication with the new drug leads to an improvement in seizure control. Any reduction in the frequency of seizures is compared against a placebo. The lack of superiority over existing treatment, combined with lacking placebo-controlled trials, means that few modern drugs have earned FDA approval as initial monotherapy. In contrast, Europe only requires equivalence to existing treatments and has approved many more. Despite their lack of FDA approval, the American Academy of Neurology and the American Epilepsy Society still recommend a number of these new drugs as initial monotherapy.

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