So, these are the lists of the different antiseizure
Let's go through treatment strategies for each of the
different type of seizure activity.
You'll also cover this lecture in your
neurology course in more detail.
Today, we're just going to focus on
the pharmacology of these drugs.
Let's start off with valproic acid. 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.
Valproic acid has a number of side effects,
and they can be quite frequent.
And in some studies we've shown up to 35 % of patients
experience some kind of side effect from valproate.
Nausea, drowsiness and vomiting via
the chemoreceptor trigger zone activation
can be experienced with patients on valproic acid.
It does have a black box warning.
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.
The first black box warning is hepatotoxicity.
The second black box warning is pancreatitis.
And the third black box warning are fetal abnormalities.
It is a class D drug.
So, we do not want to give this drug in pregnant patients.
Valproate syndrome is where the fetus has a
triangular shaped head. They often have a low IQ.
They loss the philtrum which is the little piece of folded
tissue above your lip and they have more medial eyebrows.
The next drug that I would like to discuss is clonazepam.
You can see it here being used in absence seizures
and myoclonic seizures. 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.
It is often used as a second or third line agent
because it does cause some sedation.
Let's take a look at this drug called ethosuximide. I mentioned
that earlier as being active against calcium channels.
It is the first choice for absence seizures.
It's a very effective drug for this particular problem.
It is not used in other seizure types.
It causes minimal sedation and minimal side effects.
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.
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.
So, there is a potential drug interaction
between it and other agents.
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.
We use it for myoclonic seizures, partial seizures and
tonic-clonic seizures. It's also used as an adjunctive agent.
Lamotrigine is also called Lamictal in some markets.
It's commonly used in partial seizures.
It blocks the sodium channel. And it's unique for a number
of reasons. Number 1, it has very few side effects.
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. Kids who experience
side effects are not going to take their pills.
It's very good at treating the depressive phase of bipolar
disorder. And it has been used as a mood stabilizer
for some patients. It's really the first new drug in about
30 years. Lennox-Gastaut syndrome is also treatable
with Lamictal or lamotrigine.
This is a syndrome that I encourage you to read up on
and you'll also cover this in your neurology lectures.
Let's move on to phenytoin.
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.
It's probably one of the most important drugs
in seizure control.
Phenytoin is also called Dilantin, and it's probably
the most commonly prescribed antiseizure medication.
It's used in tonic-clonic seizures
and prevention of tonic-clonic seizures.
It's used in partial seizures. And it doesn't matter
if those partial seizures are psychomotor in nature,
autonomic in nature or temporal partial seizures.
We do not use Dilantin or phenytoin in absence seizures.
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.
We don't use phenytoin in absence seizures.
It has a very narrow therapeutic index. And sometimes
we actually have to do blood levels to ensure
that we know if we're treating a person correctly or not.
Now, we do use phenytoin in cardiac arrhythmia
although that's not as common with the (inaudible) new drugs.
There is an intravenous form and that form
will work within about 20 minutes.
So, for long term seizures control in a person who has an
status epilepticus, we can use phenytoin intravenously.
Side effects are quite numerous with this medication.
One of the things that you have to be particularly
vigilant about as a practitioner is gingival hyperplasia.
It's rare but prototypical.
And that's where the gums overgrow the teeth.
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.
It can also cause a drop in your blood pressure.
One of the more feared side effects of this medication
is TEN or toxic epidermal necrolysis. 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.
And on vertical gaze, you'll develop nystagmus at toxic level.
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.
Remember that if you abruptly discontinue this medication,
you actually may precipitate seizure activity.
Let's move on to phenobarbital. 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.
Phenobarbital is a barbiturate. It acts on the GABA receptor.
Remember that barbiturate acts at a different point
on the receptor than the benzodiazepine. Phenobarb is
used in all types of seizures except for absence seizures.
Once again, that's a good exam question. It is less well
tolerated, and therefore it's our third line agent even though
it's very effective. It's our first line treatment for
neonatal seizures. And we sometimes use it for patients who
have seizure secondary to ethanol withdrawal.
And we do use it sometimes in detoxification programs.
Newer benzodiazepines have replaced the use of phenobarbital,
and that's mostly because the newer benzodiazepine
are less sedating and they work quite well. Now, remember
that phenobarb is a powerful cytochrome P450 inducer.
So, you want to be aware that this is an agent that
can change the serum levels of other drugs.
What's interesting is that it also can be used
to reduce the toxicity of other drugs.
Side effects. The bigger side effect of course is sedation and
hypnosis. And that's because it is a sedative hypnotic medication.
And please refer to our sedative hypnotic
lecture previous to get more information.
A special topic that I think we should
discuss is status epilepticus.
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.
Intravenous benzodiazepine and diazepam and lorazepam
are used because they have a very rapid onset of action.
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.
Finally, phenobarbital is particularly effective
in status epilepticus. It is very sedating
but sometimes in status,
you want to sedate the patient anyway.