Antiepileptic Drugs

by Carlo Raj, MD

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    00:01 So what is your goal in terms of management of your patient with epilepsy? Goal of drug therapy is so that you become seizure-free or at least, to limit the seizures because, remember, the Lennox Gastault, say that your child is having 200 seizures per day, huh? At this point, your first step – your first priority is, my goodness, minimize the number of seizures.

    00:25 Did you become free of seizures? Well, it’s all case dependent, isn’t it? And you want minimal side effects.

    00:32 And that’s a big deal with antiepileptic drugs as we shall see.

    00:37 Monotherapy is always preferred because the more number of antiepileptic drugs that you’re on, the cocktails will then bring about more risk for adverse effects.

    00:48 Most patients could be controlled with one drug, thank goodness.

    00:51 Treatment is generally indicated after a second unprovoked seizure because after that first one, it could be a trigger of seizure, a second that’s unprovoked, then you start thinking about management.

    01:03 Medications should not be stopped abruptly ever -- ever-- unless absolutely necessary due to the serious side effect that the patient might be experiencing.

    01:15 Let’s talk about the drugs.

    01:17 We’ll begin with phenytoin, Dilantin.

    01:22 So what does this behave like? Well, you should remember that this behaves like a sodium channel blocker, specifically, the inactivation gate.

    01:30 It kind of behaves like lidocaine, okay? But you can’t use lidocaine here.

    01:34 Use phenytoin.

    01:36 By blocking the sodium channel, hopefully , hopefully, hopefully, you’ll be able to decrease the depolarization.

    01:42 What are the types of seizures that you’re looking for primarily? Well, seizure type here for phenytoin, definitely focal.

    01:51 Focal.

    01:52 So either simple partial or complex partial.

    01:55 Generalized could be used but your focus, please, should be on partial or focal, same thing.

    02:02 Let’s talk about the side effects.

    02:05 Many of these are quite important.

    02:07 Phenytoin, up and down the body has huge issues.

    02:10 Neurologic deficits.

    02:12 You could have cardiovascular deficits.

    02:14 The gingiva could undergo hyperplasia, coarsening of the facial features.

    02:20 You could have cerebellar atrophy.

    02:22 You might have what’s known as lymphadenopathy and you could have something in a child known as your fetal hydantoin syndrome.

    02:33 Remember that? Contraindicated in pregnancy.

    02:36 But in pharmacology, if you remember, you’ve done your phenytoin in greater detail and you talked about fetal hydantoin syndrome.

    02:43 Your patient, your pregnant woman, who has been taking phenytoin, unfortunately, teratogenic and then the child that’s been born, low set ears, microcephaly, everything that you would expect with congenital issues.

    02:57 This is phenytoin.

    02:58 Also, please don’t forget in pharm, that phenytoin could be part of the HIPP, H-I-P-P, for drug-induced SLE.

    03:09 Do you remember that? What does HIPP mean? Well, hydralazine.

    03:14 I, INH.

    03:15 P, procainamide.

    03:18 Those are slow acetylators.

    03:20 Do you remember when you did pharmacokinetics? You’ve talked about slow acetylators.

    03:25 With phenytoin, it’s a little bit different, but could also result in SLE.

    03:29 Do not forget that.

    03:30 That is a clinical pearl that you want to take with you for sure.

    03:34 Let’s move on to carbamezapine, Tegretol.

    03:38 Also, mechanism action, keep it simple, sodium channel blocker.

    03:43 But the first line of treatment is a little bit different here.

    03:45 With carbamezapine, may worsen myoclonus and absence seizures, keep that in mind.

    03:52 But you could also use it for focal and then also do not forget that you could use this for trigeminal neuralgia.

    03:59 Carbamezapine, first line.

    04:01 And carbamezapine, a couple of things that are important, you must know that it may then bring about SIADH.

    04:08 In other words, it might actually increase the levels of ADH.

    04:11 And in physiology, if you remember, you are then going to increase your ECF volume, aren’t you? And once you do that, what happens to your sodium levels? Dilutional.

    04:21 Hyponatremia.

    04:23 And please, don’t forget about agranulocytosis.

    04:26 As rare as it may be, you must know it.

    04:31 Let’s talk about Depakote or valproic acid, important one.

    04:35 It could be a sodium channel blocker, kind of like your carbamezepine and phenytoin.

    04:40 And could also a GABA receptor agonist.

    04:42 Remember, what are we trying to do? You’re trying to make your patient seizure-free, if at all possible.

    04:47 What are we looking for? Well, you have all kinds of seizures here.

    04:50 You can have partial with generalized or absence.

    04:54 Side effects here would be weight gain, tremor, hair loss.

    04:57 In other words, alopecia, okay? Alopecia.

    05:03 Whereas with phenytoin, it would be hirsutism.

    05:08 Okay, so phenytoin and valproic acid, a little bit different.

    05:11 Take the P in valproic or Depakote and alopecia, means hair loss.

    05:17 Next, another big one is called the hepatotoxicity.

    05:22 In fact, the liver might die quite early.

    05:25 And there is a gene here, in which we’ll take a look at, known as your polymerase gamma, okay? Polymerase gamma, POLG.

    05:34 And that’s new information that you want to keep in mind because that hepatotoxicity is a big one, ladies and gentlemen, and it’s called hepatotoxicity, don’t forget that.

    05:44 Along with this, there’s something else that I want to bring to your attention.

    05:47 It’s also contraindicated in pregnancy.

    05:50 So now, we have two drugs that I’ve mentioned to you that are contraindicated in pregnancy that you must know for your boards and wards.

    05:58 With phenytoin, we call that fetal hydantoin syndrome and the child there would look like microcephaly, low set ears, which you would expect with congenital issues.

    06:06 With valproic acid, as sad it may seem, let me give you a description.

    06:13 You know what this means? Okay, so I’m referring to Spock.

    06:17 But what’s the show, a movie? Star Trek.

    06:19 In Star Trek, there’s a character, his name is Klingon-- or the species.

    06:24 What do you know about this Klingons? If you know nothing about this, don’t worry about it.

    06:27 The point is they have the front of the head, the frontal regions, in which it looks like it’s protruding.

    06:33 In other words, there is premature closing of the frontal bone.

    06:37 Therefore, causing protrusion of the frontal area.

    06:41 It looks like a Klingon, that’s unfortunate.

    06:43 We call this trigonocephaly.

    06:46 That’s new information that you want to keep in mind, please, as you know about valproic acid.

    06:52 Now, let’s quickly walk through some barbiturates.

    06:55 Phenobarbital, barbiturates, what does that do? GABA receptor agonist.

    07:00 is this going to increase the duration or the frequency? Yes, it increases the duration of your GABA receptor being open, so that chloride can come in, right? Remember that from pharm.

    07:11 Partial, generalized.

    07:12 Sedation, mild addiction potential, always, always with barbiturates.

    07:16 And my goodness gracious, once we have addiction kicking in, then what are you worried about with pheno? The barbiturates may then cause impediment or inhibition of your respiratory center.

    07:26 Not good, not good.

    07:28 Keep things in mind, please.

    07:29 As I said, monotherapy would be the preferred method of management of epilepsy.

    07:34 Take a look at the side effects, man.

    07:37 Pretty severe, huh? Pretty severe.

    07:40 Ethosuximide.

    07:42 You pay attention to your letter T here.

    07:44 Ethosuximide, called Zarontin.

    07:47 The reason for the T is because where are we once again? In the head.

    07:51 That’s your problem.

    07:52 So when you say T type, why would you talk about the T-type calcium channels in the heart? You know what I’m saying? So you’re going to use the T type calcium channels where? In the? Good.

    08:04 Thalamus.

    08:05 That’s where you’re going to inhibit the calcium channel.

    08:08 Use the T in ethosuximide to then help you understand or memorize the mechanism of action.

    08:16 It is the drug of choice for absence.

    08:18 What does that mean to you? In childhood, generalized seizure in which the patient is staring off into space for seconds.

    08:26 Side effect: GI Gabapentin.

    08:30 Partial, focal.

    08:31 Sedation, ataxia, weight gain at high doses.

    08:35 Gabapentin, Neurontin.

    08:39 This is lamotrigine.

    08:41 These are some of your other drugs that you want to keep in mind.

    08:44 It could be a sodium channel blocker or a glutamate antagonist.

    08:49 Partial with generalized and risk here, at least know Steven-Johnsons syndrome.

    08:54 What does that mean to you? Is that dangerous? Yeah, absolutely.

    08:58 Why? Increases the risk of mortality.

    09:02 You’ve heard of Steven-Johnsons syndrome.

    09:04 You’ve heard of toxic epidermal necrolysis.

    09:08 Know that for lamotrigine, please.

    09:10 We have another one called tiagabine.

    09:13 GABA receptor.

    09:15 What are you trying to do? Slow down the partial seizures.

    09:19 Sedation.

    09:22 Topamax or topiramate.

    09:25 Really here, it may be blocking your glutamate, partial with generalized, weight gain, and make sure you know about renal stones.

    09:35 That’s the clinical pearl here.

    09:37 You have another one called zonisamide.

    09:39 T type calcium channel.

    09:41 When did we last see this? With ethosuximide, T type.

    09:46 Partial, generalized, weight gain and you could also see renal stones.

    09:51 Topiramate and zonisamide.

    09:55 And we have Felbatol.

    09:57 Just a couple of things here.

    09:58 I’m going through this quickly because here, the amount of detail that you want to know is minimal.

    10:06 The amount of time that I spent with phenytoin, carbamezapine, valproic acid and such, that’s where you want to spend time.

    10:12 But just to make sure we’re complete, I’m walking you through all antiepileptics.

    10:17 Here, you want to know about liver failure and aplastic anemia, please.

    10:22 Felbamate.

    10:23 Those are important.

    10:24 A couple words of our last antiepileptic drug that we’ll take a look at, levetiracetam.

    10:29 In terms of its mechanism of action, there are many theories out there.

    10:32 Anything that would slow down your seizures would obviously be the answer choice.

    10:39 Partial with generalized, somnolence would be a side effect.

    10:42 And self-limited, rare, but could occur, known as akathisia.

    10:47 In other words, movement disorder.

    About the Lecture

    The lecture Antiepileptic Drugs by Carlo Raj, MD is from the course Seizures.

    Included Quiz Questions

    1. Gingival hyperplasia
    2. Hepatomegaly
    3. Ptosis
    4. Dental caries
    5. Splenomegaly
    1. Sodium channel blocker
    2. Sodium channel enhancer
    3. Calcium channel blocker
    4. Potassium channel blocker
    1. Premature closure of the frontal bones
    2. Delayed closure of the frontal bones
    3. Premature closure of the temporal bones
    4. Premature closure of the orbital bones
    5. Premature closure of the occipital bones
    1. Polymerase gamma gene mutation
    2. Polymerase alpha gene mutation
    3. Polymerase beta gene mutation
    4. Polymerase kappa gene mutation
    5. Polymerase gamma gene absence

    Author of lecture Antiepileptic Drugs

     Carlo Raj, MD

    Carlo Raj, MD

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