Seizures: Treatment

by Roy Strowd, MD

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    00:01 So once we've made a diagnosis and we've evaluated the patient's seizure with EGG, we need to treat the patient.

    00:07 And what are some of the treatments that we can consider in patients with a diagnosis of seizure or epilepsy? Well, there are a lot.

    00:14 And if we go through the list it's quite long.

    00:16 Phenobarbital, Primidone, Phenytoin and Ethosuximide, Carbamazepine, Valproic acid, Lamotrigine, Topiramate, Oxcarbazepine, Levetiracetam, Zonisamide, Pregabalin, Lacosamide, Felbamate, Rufinamide, Vigabatrin, Tiagabine, Gabapentin.

    00:34 And there are even more that are on this list that I'm not even able to include or newer agents that are being developed.

    00:39 The list is quite long, and it would be very difficult to go through the mechanism of action.

    00:44 The potential side effects and the seizure types that are best treated with each of these medicines by just going through the laundry list independently.

    00:53 So when I'm thinking about the seizure medicines, I like to organize them by their mechanism of action.

    00:59 And we can see here some of the categories of these medications by mechanism of action.

    01:04 We'll start with the GABAergic drugs.

    01:07 This is a list of commonly used antiepileptics that act by increasing GABAergic tone inhibitory tone.

    01:15 Seizures occur because of excess excitatory tone.

    01:19 And the treatment here is in to increase GABAergic or inhibitory tone.

    01:24 And we can see those medicines include phenobarbital, primidone, the benzodiazepines, and then to less commonly used medications but in for important seizure medicines, tiagabine and vigabatrin.

    01:37 And each of these medicines act by either binding at the GABA receptor or increasing circulating GABA neurotransmission in the brain, increasing inhibitory tone.

    01:47 The side effect of these medicines is typically sedation, that's one of the more common side effects that we see with this class of medicines.

    01:55 When we're increasing GABA tone to reduce seizures, we can increase inhibitory tone throughout the brain, and the side effect is sedation.

    02:04 The second category that we see are the sodium channel active agents.

    02:08 Sodium is critical in neurotransmission.

    02:11 We saw that in when thinking about the action potential and the development of seizures.

    02:17 And there's a list of medicines that act primarily through sodium channel activity.

    02:22 You can see phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, topiramate and zonisamide and each of these medicines has a primary mechanism of action through the sodium channels.

    02:35 Sodium channel active agents also has a list of side effects that we see when attacking the sodium channel.

    02:41 And those are typically nausea, vomiting, dizziness, ataxia or imbalance.

    02:45 And sometimes cardiac issues, which we can see here with lacosamide.

    02:50 This group of medications include some of the older seizure medications like phenytoin and carbamazepine which have prominent hepatic metabolism, and then some of the newer agents like oxcarbazepine, lamotrigine, lacosamide, topiramate, and zonisamide.

    03:06 The third category we see are the calcium channel activations.

    03:10 And ethosuximide is probably the prototypical calcium channel, active agent.

    03:15 Ethosuximide acts on the T-type calcium channels and is important in primary generalized epilepsies.

    03:21 It's used to treat absence epilepsy.

    03:24 There's also 2 other medicines that fall into this category that you wouldn't think about, and that's a gabapentin, and pregabalin.

    03:31 We typically think of these medicines as increasing GABAergic tone, increasing inhibitory tone, and they do, but they actually don't act through GABA.

    03:41 They act on the voltage-gated calcium channels.

    03:44 And so these 2 GABA drugs act on the calcium channels, but really worked to increase inhibitory tone in the brain.

    03:51 And so their side effects really look more like the GABAergic agents, then the calcium channel agents like ethosuximide.

    03:59 The next category of their carbonic anhydrase inhibitors, and this is not the mechanism of their anti-seizure control.

    04:05 But this is one of the important side effects that is derived from the carbonic anhydrase activity and that's topiramate and zonisamide.

    04:14 These medicines can act at the renal tubules and cause increase acid production or acidemia, decreased sweating, and they can be used in some cases to reduce CSF of production as in patients with pseudotumor cerebri.

    04:29 Levetiracetam acts through the SV2A or synaptic vesicle protein.

    04:34 This is a very novel mechanism of action.

    04:37 Levetiracetam is also often combined with other seizure medicines for rational polypharmacy because it's really the only drug that acts through this channel.

    04:46 It is a very safe and well tolerated medication with very few side effects.

    04:50 Sedation we can see with all anti-epileptics.

    04:53 And about 5 to in some cases in kids 25% of patients can have some problems with mood and increased mood and irritability or agitation with levetiracetam.

    05:04 Valproic acid has many mechanisms of action, it doesn't really fit well into a single bucket.

    05:09 We see a number of side effects that are both unique to valproic acid and can be seen with other agents.

    05:14 Some of those unique valproic acid side effects are weight gain or hair loss.

    05:19 It can also cause idiosyncratic pancreatitis.

    05:21 So it's an important medicine that we monitor.

    05:23 And it is metabolized hepatically through the liver, and that's important to monitor in patients who are being treated with valproic acid for any indication.

    05:32 And then the last 2 categories are the potassium channel active agents.

    05:35 This is one of the newer seizure medications "Potiga", which acts to the potassium channel in Q2 channel.

    05:43 And then there are a couple of other medicines that don't fall well into a mechanism of action specific categorization.

    05:49 And that would be felbamate and rufinamide.

    About the Lecture

    The lecture Seizures: Treatment by Roy Strowd, MD is from the course Seizures and Epilepsy.

    Included Quiz Questions

    1. Phenytoin
    2. Primidone
    3. Ethosuximide
    4. Phenobarbital
    5. Gabapentin
    1. Ataxia
    2. Mood changes
    3. Sedation
    4. Acidemia
    5. Decreased sweating
    1. Valproate
    2. Zonisamide
    3. Gabapentin
    4. Carbamazepine
    5. Phenobarbital

    Author of lecture Seizures: Treatment

     Roy Strowd, MD

    Roy Strowd, MD

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