Epilepsy antiseizure drugs

FIGURE 37-4 Antiseizure mediated reduction of IT. Certain antiseizure drugs reduce the flow of calcium through T-type Ca2+ channels (ethosuximide, valproate), thereby reducing the pacemaker current that underlies spike-wave discharges of generalized absence epilepsy. 

The antiseizure drugs described in this chapter are also used in patients with febrile seizures or with seizures occurring as part of an acute illness such as meningitis. The term "epilepsy" is not usually applied to such patients unless chronic seizures develop later. Seizures are occasionally caused by an acute underlying toxic or metabolic disorder, in which case appropriate therapy should be directed toward the specific abnormality, eg, hypocalcemia. In most cases of epilepsy, however, the choice of medication depends on the empiric seizure classification. 

Rufinamide is a new triazole derivative with little similarity to other antiseizure drugs. It is approved for use in Lennox-Gastaut syndrome and preliminary evidence suggests that it may also be useful in other difficult-to-treat epilepsy syndromes. 

Because of the heterogeneity of epilepsy, complete discontinuance of antiseizure drug administration is an especially difficult problem. If a patient is seizure-free for 3 or 4 years, a trial of gradual discontinuance is often warranted. 

In dealing with the clinical problem of a pregnant woman with epilepsy, most epileptologists agree that while it is important to minimize exposure to antiseizure drugs, both in numbers and dosages, it is also important not to allow maternal seizures to go unchecked. 

NATURE AND MECHANISMS OF SEIZURES AND ANTISEIZURE DRUGS PARTIAL EPILEPSIES... 

THERAPEUTIC USE TOXICITY The addition of levetiracetam to other antiseizure medications in adults with refractory partial seizures improved control in one clinical trial. Insufficient evidence is available on use of levetiracetam as monotherapy for partial or generalized epilepsy. The drug is well tolerated adverse effects include somnolence, asthenia, and dizziness. 

The antiseizure drugs introduced after 1990 have teratogenic effects in animals but whether such effects occur in humans is uncertain. One consideration for a woman with epilepsy who wishes to become pregnant is a trial period without antiseizure medication monotherapy with careful attention to drug levels is another alternative. Polytherapy with toxic levels should be avoided. Folate supplementation (0.4 mg/day) is recommended for all women of childbearing age to reduce the likelihood of neural tube defects, and this is appropriate for epileptic women as well. 

The ability of conotoxins to selectively block ion channels and neuronal receptors has led to their development into therapeutic agents. So far, most conotoxin applications as therapeutics have been concentrated on the treatment of different forms of pain. The first drug of marine origin is based on the w-conotoxin MVIIA for the treatment of chronic pain (see helow). Other therapeutic applications of conotoxins include treatment of schizophrenia, epilepsy, neuromuscular disorders, certain types of cancer, urinary dysfunction, Parkinson s disease, Alzheimer s disease, stroke, and related hrain injuries. Other uses include muscle relaxants, anesthetics, and antiseizure compounds. As the demand for new painkillers and other neuropharmacological agents is expected to increase, the value of the discovery and testing of new conotoxins is expected to continue to expand. 

---