1. ANTI-SEIZURE MEDICATIONS
By: Jennipher Orellana

2. Meet identical twins, Andrea and Adriana.
Valproic Acid, Topiramate, Lavetiracetam, Clobazam (Benzodiazepine)
They both had their first seizure at 6 mths old. They were diagnosed with Epilepsy. Still don’t know what triggered it. They have been on Anti-Seizure medications for the last 24 plus years.
They are my little sisters and today we get to see how these medications aim to relieve the symptoms of their Epilepsy.

3. It all starts with a Presynaptic Neuron…
Excitatory Neuron releases an excitatory neurotransmitter, like Glutamate, which increases the probability of an action potential being passed on to postsynaptic neuron by opening the ligand-gated sodium channels. As a result of increased sodium ion flow, the membrane becomes less negative/more positive inside. This depolarization is called Excitatory Post Synaptic Potential because it’s “exciting” the post synaptic neuron.
Inhibitory Neuron makes sure that excitation stops whenever it needs to so brain can function properly. When activated, it releases neurotransmitter, Gamma-Aminobutyric Acid (GABA), which causes an opening in ligand-gated K+ ion channels which leads to hyperpolarization, or Inhibitory Post Synaptic Potential (IPSP)

4. Seizure: results from uncontrolled excitation of brain neurons.
Epilepsy: chronic neurological disorder, characterized by recurrent, sudden discharge of excessive electrical energy (seizure) from nerve cells located within the brain.
Seizure: results from uncontrolled excitation of brain neurons.
Epilepsy has no identifiable cause in about half of those with condition.
Up to 500 genes could be tied to condition and can make a person more sensitive to environmental conditions that trigger seizures.
Head Trauma, Brain Conditions (tumors, strokes), Infectious Diseases (meningitis, AIDS, viral encephalitis), Prenatal Injury (infection in the mother, oxygen deficiencies), or Developmental Disorders (Autism, Neurofibromatosis)

5. Drugs that treat seizures: Block channels in the cell membrane or alter their receptor sites and aim to stabilize the resting potential of neurons (decrease/inhibit excitability).
Can be classified into:
Drugs that control or modify voltage-gated channels (Na+, Ca+)
Drugs that inhibit/stop synaptic excitement (blocks glutamate)
Drugs that make synaptic inhibition signals stronger (enhance GABA)

6. Sodium Channel Blockers
These Medications prevent the return of Sodium Channels to the active state by stabilizing them in the inactive state. This prevents repetitive firing (high frequency) of the axons.
Carbamazepine, Phenotoyn, and Lamotrigine, Valproate (Valproic Acid), Zonisamide block Sodium voltage channels, stopping depolarization (a less negative environment) of presynaptic Glutamatergic neuron.

7. Calcium Channel Blockers
Influx of calcium through these channels in resting membrane state produces partial depolarization of membrane, facilitating development of action potential.
Ethosuximide and Valproate lock Ca+ channels, inhibiting slow depolarizations necessary to generate currents.

8. Glutamate Blockers
Glutamate: main excitatory neurotransmitter released by nerve cells and under normal conditions plays important role in learning and memory.
Glutamate Receptors: particularly concerned with the AMPA and NMDA receptors in this case, as they specialize in excitation, producing excitatory electrical responses.
Felbamate, Levetiracetam, Topiramate modify these receptors which will affect either activation, inactivation, conductance, and/or ion permeability.

9. GABA Enhancers
Gamma-Aminobutyruc Acid (GABA): Chief inhibitory neurotransmitter in Central Nervous System. Principle role is reducing neuronal excitability.
GABA system can be enhanced by Barbiturates & Benzodiazepines enhancing binding directly to GABA-A receptors, enhancing CL_ influx which increases negativity of cell which increases difficulty of reaching action potential
Tiagabine will inhibit the reuptake of GABA, resulting in more GABA activity in synaptic cleft.
Vigabatrin and Valproate will inhibit the GABA-transaminase (enzyme), so more GABA will be available (because less is being broken down), resulting in more GABA activity in Synaptic Cleft.

10. Sex Hormones
Progesterone is a natural anticonvulsant that acts by increasing chloride conductance GABA-A receptors (increasing negativity of cell) and reduces Glutamate’s excitatory response.
In contrast, Estrogen reduces Cl-conductance and acts as an agonist for Glutamate’s NMDA receptor, triggering seizures if threshold is reached.

13. Conclusion…
These drugs can decrease the frequency and/or severity of seizures in people with Epilepsy.
They treat the symptoms only. They do not cure.
Their Goal is to maximize quality of life by minimizing seizures and adverse drug effects.
Side effects of these drugs can be serious: Hepatic damage, sedation, fatigue, blurred vision, tremors, mental/motor slowing or impairment, altered connective tissue metabolism or growth, gingival hyperplasia, Hirsutism… and many more.