Treatment of Epilepsy: Preoperative Evaluation

Drugs targeting the Na⁺ channel reduce the likelihood of a seizure by either increasing the amount of time the channel stays in the inactive state or by altering the shape of the Na⁺ channel. In both cases, the drugs prevent sustained repetitive firing of the cells. Likewise, Ca²⁺ channel blockers are used to block T-type Ca²⁺ channels or high-voltage activated channels, resulting in decreased excitability of the cells. Ca²⁺ is also critical in the release of a neurotransmitter from synaptic vesicles. Reducing release of glutamate would reduce the likelihood of a seizure. Levetiracetam binds to synaptic vesicles and appears to reduce seizure frequency by altering the release of neurotransmitters from synaptic vesicles.

Blocking excitation through the NMDA, AMPA, and kainate receptors can reduce excitation by reducing the inward flow of Na⁺ and Ca²⁺ ions. Likewise, drugs acting on GABA_A receptors facilitate the passage of Cl⁻ into cells. Their passage into the cell makes the resting membrane potential more negative inside the cell and makes it more difficult for the cell to depolarize. The GABA_A receptor has benzodiazepine and barbiturate receptor sites. Activation of the benzodiazepine receptor enhances the frequency of openings of the GABA_A receptor. Activation of the barbiturate receptor increases the duration of openings of the GABA_A receptor. The GABA effect can also be increased by blocking reuptake of GABA by neurons and glia, increasing the concentration of GABA at postsynaptic receptors, or reducing GABA breakdown in the neurons through inhibition of GABA transaminase.

The ketogenic diet is typically used to treat children with severe epilepsy who do not respond to antiepileptic drugs. The ketogenic diet consists of a high proportion of fats and small amounts of carbohydrate and protein. The basis of the therapeutic effectiveness of the ketogenic diet is thought to be the ketosis that develops when the brain is relatively deprived of glucose as an energy source and must shift to use of ketone bodies as the primary fuel.

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