00:01
So let's talk about
some common tips.
00:03
So the top 10 seizure
treatment tips
when we're selecting
and using medications.
00:10
So let's talk about some
seizure tips or clinical pearls
to think about when selecting
a seizure treatment.
00:17
And we'll go through some cases.
00:19
The first is a 13-year-old boy,
who's referred from his PCP.
00:23
The 13-year-old boy presents
to the ED on referral from his PCP.
00:27
He initially presented
with problems in school,
staring about eight months ago.
00:31
Initially was diagnosed with ADD
but recently there's been
some concern for seizures.
00:37
He's also has depressed mood
and at times is reported to have
episodes of pressured speech
and grandiose behavior.
00:43
He was placed on Tegretol
three weeks ago,
as he was not able to get
and see a neurologist
for another two months.
00:49
Unfortunately, he has developed
seizures that have worsened
and have now had five spells a day,
where he was only having
up to 1 to 2 weeks before.
00:59
So what's going on in this case?
Well,
this is someone,
who initially had episodes
of behavioral arrest
that were thought to be from ADD,
but were likely
underlying seizures.
01:10
He was placed on carbamazepine,
and then those episodes
worsened in frequency.
01:15
This is a key clinical pearl
about what medications worsen
primary generalized seizures.
01:20
The clinical description
is consistent
with a generalized onset epilepsy.
01:25
And here we see
one of the common offenders.
01:28
These medications include
carbamazepine, as in this case.
01:31
Vigabatrin, gabapentin,
Trileptal or oxcarbazepine,
and Tiagabine.
01:37
These are medications
that we don't tend to use
for primary generalized epilepsy.
01:42
We can in selected cases,
but we don't tend to because they
can worsen those patients seizures.
01:46
A good clinical pearl.
01:50
Let's consider
a 34-year-old woman
with a long history
of temporal lobe epilepsy
who presents to the ED
in status epilepticus.
01:57
She developed progressively
worsening complex partial seizures
over the past six months.
02:02
She's been on phenytoin
and for many years.
02:04
Given an increase
in seizure frequency,
her phenytoin has gradually
been increased and increased
to a serum level around 25.
02:11
With continued seizures,
valproic acid is added three days
prior to her presentation.
02:17
You recommend that
the ED checker levels
to determine compliance.
02:20
Her total phenytoin level is high.
02:23
Her valproic acid level is normal.
02:26
So what antiepileptic
medications have strong
protein-protein interaction?
And that's what's going on
with this patient.
02:33
Phenytoin and valproic acid
have protein-protein binding
and both interact.
02:38
When we add the
valproic acid to the phenytoin
the valproic acid binds to protein
more than phenytoin
and we see an increase
in the free phenytoin level.
02:49
Protein binding is important
for medications
like phenytoin and valproic acid.
02:53
Valproic acid has a greater
affinity to protein than phenytoin.
02:58
And adding valproic acid
to phenytoin
displaces the phenytoin in from
its bound state on the protein,
resulting in a
lower serum concentration,
but higher free drug levels.
03:08
And so patients can become
phenytoin toxic.
03:12
Let's consider
a 28-year-old woman
who presents for management
of a known seizure disorder.
03:17
She has been on
Topamax for three years
and was tolerating it well.
03:21
But his reporting increased issues
with difficulty with her thinking.
03:24
She's interested in
changing medications
and is wondering about
carbamazepine or Tegretol.
03:29
Given associated mood
complaints that she has.
03:32
You agree starter on
200 milligrams twice a day,
and titrate up to 400 milligrams
twice a day after one week.
03:40
You see the patient back
after three months,
and she says,
that at first, she felt horrible.
03:44
Had intense vomiting
sodium channel side effects
after each dose
of the medication.
03:49
But over time, this resolved.
03:51
Now, she's concerned that
the medication is not working,
because she's back to having
one to two light seizures per week.
03:57
So what's going on
with this patient?
Well, this is a great example of
what anti-seizure medicines
are associated with
hepatic auto-induction?
And the one to remember
is carbamazepine.
04:10
Carbamazepine causes
auto-induction.
04:12
It induces the expression of
the CYP3A4 enzyme in the liver.
04:17
This enzyme is involved in
metabolism of carbamazepine.
04:20
So as the medication is initiated,
the liver at the first doses doesn't
have the CYP3A4 enzyme around.
04:27
So it's not rapidly metabolized.
04:30
Over time as the liver becomes
used to the carbamazepine,
there's increased expression
of the CYP3A4 enzyme.
04:37
Increased metabolism
of the carbamazepine
and lower drug levels.
04:42
So carbamazepine is typically
a drug that we start
over the first couple of weeks
and check a level
after several weeks,
and would plan to further
titrate the medication
based on the degree of
hepatic auto-induction.
04:53
And this is a great clinical example
of what's going on for this patient.
04:58
And then, let's consider
an 18-year-old woman
who presents to your clinic
six months after
a new patient appointment
for a treatment evaluation
of seizures.
05:06
She's very furious.
05:08
She says that she is not married
and has become pregnant
since you saw her last.
05:13
She has been on
birth control pills, consistently
over this period of time
and is not sure how this happened.
05:19
And she blames you.
05:21
This is a good example of
counseling needed for patients
when we're starting selected
seizure medications.
05:26
We must warn our patients
about the potential
of oral contraceptive failure
on selected agents.
05:32
So what are those
anti-seizure medications
that can interfere with activity
of oral contraceptive pills?
Well, here's a list.
05:40
Levetiracetam,
gabapentin, tiagabine,
vigabatrin, zonisamide,
topiramate,
all of those medications
have no effect on endogenous
steroid hormone concentrations.
05:50
They're okay to use
without seeing problems
with oral contraceptive pills.
05:55
The medications that can
cause contraceptive failure
are lamotrigine, phenytoin,
phenobarbital, and carbamazepine.
06:03
And important to counsel patients
when starting these medications.
06:08
And then let's consider
a 13-year-old boy
with mild mental retardation
who presents for
a return appointment
for management of medically
refractory generalized epilepsy.
06:17
He was on Lamictal monotherapy
and things were stable on this
medication for many years,
until recently.
06:23
His mother called with
increased seizure frequency
and breakthrough seizures
about one month ago.
06:29
He's six inches taller and
skinnier at this visit then last.
06:32
His mother was concerned about
increased seizure frequency
and asked and to start him
on an additional medication.
06:38
You recommend valproic acid.
06:40
She says, that since that,
since starting valproic acid
over the past week,
he's been sleepy or and sleeper,
and seemed somewhat confused.
06:49
So what anti-seizure medication
is associated with hyperammonemia?
That's what's going
on in this case.
06:55
Hyperammonemia is associated
with valproic acid.
06:58
This is a medication that
can be associated with
idiosyncratic pancreatitis
and hepatitis
as well as, as spontaneous increases
in circulating ammonia levels.
07:09
Hyperammonemia can occur in
the absence of transaminitis
or other LFT abnormalities.
07:14
And we note that this can be
particularly the case
when valproic acid is combined
with lamotrigine
where there is
drug-drug interaction.
07:21
So this is a good example
of a patient
who's suffering from
hyperammonemic-induced
encephalopathy
that was precipitated
by the combination
of valproic acid and lamotrigine.