Treatment Strategies – Antiseizure Medications

by Pravin Shukle, MD

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    00:01 So, these are the lists of the different anti-seizure medications.

    00:04 Let's go through treatment strategies for each of the different type of seizure activity.

    00:09 You will also cover this lecture in your neurology course in more detail.

    00:15 Today, we're just going to focus on the pharmacology of these drugs.

    00:18 Let's start off with valproic acid.

    00:21 So, you can see that it's used in multiple different treatment strategies, right from absence seizures or myoclonic seizures to partial and tonic-clonic seizures.

    00:32 Valproic acid has a number of side effects, and they can be quite frequent.

    00:38 And in some studies we've shown up to 35 % of patients experience some kind of side effect from valproate.

    00:44 Nausea, drowsiness and vomiting via the chemoreceptor trigger zone activation can be experienced with patients on valproic acid.

    00:54 It does have a boxed warning, also called black box warning.

    00:58 What a black box warning means is, is that the regulatory agencies have put it and mandated that all people be aware of potential problems of these drugs.

    01:08 The first black box warning is hepatotoxicity.

    01:11 The second black box warning is pancreatitis.

    01:16 And the third black box warning are fetal abnormalities. It is a class D drug.

    01:23 So, we do not want to give this drug in pregnant patients.

    01:26 Valproate syndrome is where the fetus has a triangular shaped head.

    01:32 They often have a low IQ.

    01:34 They loss the philtrum which is the little piece of folded tissue above your lip and they have more medial eyebrows.

    01:41 In 2015, the FDA made a significant move to update the pregnancy risk information associated with medications.

    01:48 The outdated letter system, which classified drugs into categories A, B, C, D, and X, was replaced by the Pregnancy and Lactation Labeling Rule (PLLR).

    01:59 Under PLLR, more specific information is given in narrative form about the risks and effects of a drug in pregnancy, during lactation, and on reproductive potential. The old FDA system is still used in some countries.

    02:14 The next drug that I would like to discuss is clonazepam.

    02:17 You can see it here being used in absence seizures and myoclonic seizures.

    02:22 Clonazepam has a specific activity, once again on the GABA channel, remember that a benzodiazepine will increase the frequency of opening of this channel, allowing chloride to pass through.

    02:34 It is often used as a second or third line agent because it does cause some sedation.

    02:40 Let's take a look at this drug called ethosuximide.

    02:45 I mentioned that earlier as being active against calcium channels.

    02:49 It is the first choice for absence seizures.

    02:52 It's a very effective drug for this particular problem.

    02:55 It is not used in other seizure types.

    02:59 It causes minimal sedation and minimal side effects.

    03:02 It can interact with valproic acid, but we still use it with caution in combination because the protective index of this drug is so high.

    03:12 One of the things you have to be aware of when you're talking about this molecule is that it actually can increase phenytoin levels as well.

    03:20 So, there is a potential drug interaction between it and other agents.

    03:25 Let's move on to lamotrigine. So, when you look at this set of slide, you can see that lamotrigine is used extensively in epilepsy.

    03:35 We use it for myoclonic seizures, partial seizures and tonic-clonic seizures.

    03:40 It's also used as an adjunctive agent.

    03:43 Lamotrigine is also called Lamictal in some markets.

    03:49 It's commonly used in partial seizures.

    03:51 It blocks the sodium channel.

    03:53 And it's unique for a number of reasons.

    03:56 Number 1, it has very few side effects.

    03:58 And that's like gold in epilepsy, right? Remember that a lot of epilectics are kids, so we want to make sure that they stay on their medications.

    04:07 Kids who experience side effects are not going to take their pills.

    04:11 It's very good at treating the depressive phase of bipolar disorder.

    04:16 And it has been used as a mood stabilizer for some patients.

    04:21 It's really the first new drug in about 30 years.

    04:24 Lennox-Gastaut syndrome is also treatable with Lamictal or lamotrigine.

    04:30 This is a syndrome that I encourage you to read up on and you will also cover this in your neurology lectures.

    04:37 Let's move on to phenytoin.

    04:41 Now, I just want to mention something very briefly, just because phenytoin is at the bottom of this list, does not mean that it's not an important drug.

    04:48 It's probably one of the most important drugs in seizure control.

    04:53 Phenytoin is also called Dilantin, it's used in tonic-clonic seizures and prevention of tonic-clonic seizures.

    05:01 It's used in partial seizures.

    05:03 And it doesn't matter if those partial seizures are psychomotor in nature, autonomic in nature or temporal partial seizures.

    05:11 We do not use Dilantin or phenytoin in absence seizures.

    05:17 This is going to be an important exam question at every stage of your training whether it's the USMLE or the MCCQE, or if it's your final exam to become a specialist.

    05:29 We don't use phenytoin in absence seizures.

    05:33 It has a very narrow therapeutic index.

    05:35 And sometimes we actually have to do blood levels to ensure that we know if we're treating a person correctly or not.

    05:42 Now, we do use phenytoin in cardiac arrhythmia although that's not as common with the advent of some new drugs.

    05:49 There is an intravenous form and that form will work within about 20 minutes.

    05:55 So, for long term seizures control in a person who has an status epilepticus, we can use phenytoin intravenously.

    06:03 Side effects are quite numerous with this medication.

    06:08 One of the things that you have to be particularly vigilant about as a practitioner is gingival hyperplasia. It's rare but prototypical.

    06:16 And that's where the gums overgrow the teeth.

    06:20 The reason why I want to mention this to you is because if you have a patient picture on your exam with gingival hyperplasia where the gum seem to be hypertrophic, think about this drug. Remember that it is a category D drug, and remember that can also cause bone marrow suppression.

    06:39 It can also cause a drop in your blood pressure.

    06:42 One of the more feared side effects of this medication is TEN or toxic epidermal necrolysis.

    06:51 One of the interesting things about this drug and it's very common on exams is that at lateral gaze, you will develop nystagmus when you're at a proper therapeutic level.

    07:03 And on vertical gaze, you will develop nystagmus at toxic levels.

    07:08 So, it's really nice quick and dirty trick to do in your office to determine whether or not the patient is on adequate doses of phenytoin or not.

    07:16 Remember that if you abruptly discontinue this medication, you actually may precipitate seizure activity.

    07:24 Let's move on to phenobarbital.

    07:26 Phenobarbital, once again, just because it's on the bottom of the list, doesn't mean it's not important, it also is one of the most important agents that we use to treat seizures.

    07:35 Phenobarbital is a barbiturate. It acts on the GABA receptor.

    07:40 Remember that barbiturate acts at a different point on the receptor than the benzodiazepine.

    07:46 Phenobarb is used in all types of seizures except for absence seizures.

    07:51 Once again, that's a good exam question.

    07:54 It is less well tolerated, and therefore it's our third line agent even though it's very effective.

    07:59 It's our first line treatment for neonatal seizures.

    08:02 And we sometimes use it for patients who have seizure secondary to ethanol withdrawal.

    08:10 And we do use it sometimes in detoxification programs.

    08:15 Newer benzodiazepines have replaced the use of phenobarbital, and that's mostly because the newer benzodiazepine are less sedating and they work quite well.

    08:26 Now, remember that phenobarb is a powerful cytochrome P450 inducer.

    08:32 So, you want to be aware that this is an agent that can change the serum levels of other drugs.

    08:39 What's interesting is that it also can be used to reduce the toxicity of other drugs.

    08:45 Side effects. The bigger side effect of course is sedation and hypnosis.

    08:51 And that's because it is a sedative hypnotic medication.

    08:54 And please refer to our sedative hypnotic lecture previous to get more information.

    09:00 A special topic that I think we should discuss is status epilepticus.

    09:05 Now, status epilepticus is going to be covered in more detail in your neurology lecture, I'm not going to get into too much detail here except just to talk about the drugs.

    09:14 Intravenous benzodiazepine, like diazepam and lorazepam are used because they have a very rapid onset of action.

    09:22 Intravenous phenytoin is next in line in terms of how quickly it affects you, it also has cardiotoxicity and you need to be aware of that.

    09:33 Finally, phenobarbital is particularly effective in status epilepticus.

    09:37 It is very sedating but sometimes in status, you want to sedate the patient anyway.

    About the Lecture

    The lecture Treatment Strategies – Antiseizure Medications by Pravin Shukle, MD is from the course CNS - Pharmacology. It contains the following chapters:

    • Absence Seizures
    • Clonazepam
    • Ehtosuxamide
    • Lamotrigine
    • Phenytoin
    • Phenobarbital
    • Status Epilepticus

    Included Quiz Questions

    1. Valproate should not be used to treat pregnant women.
    2. Valproate can be used in pregnancy as long as fetal growth is closely monitored by ultrasound.
    3. Valproate should not be used to treat pregnant women with bipolar disorder.
    4. Folic acid coadministration can reduce the risk of congenital neural tube defects.
    5. Despite causing congenital malformations, valproate does not affect IQ.
    1. Ethosuximide
    2. Lithium
    3. Valproate
    4. Phenytoin
    5. Lamotrigine
    1. Absence seizures
    2. Neonatal seizures
    3. Tonic-clonic seizures
    4. Partial seizures
    5. Myoclonic seizures
    1. Intravenous benzodiazepines
    2. Oral benzodiazepines
    3. Phenobarbital
    4. Oxygen
    5. Phenytoin

    Author of lecture Treatment Strategies – Antiseizure Medications

     Pravin Shukle, MD

    Pravin Shukle, MD

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