Neurology Flashcards by Aidyl XXX

Q

E.S. is a 25-year-old electrician. He has had several
episodes of memory lapses. His wife reports
lip smacking and chewing movements during these
spells. An electroencephalogram (EEG) reveals
focal epileptiform spike waves. Which medication
would be best for E.S.?
A. Ethosuximide.
B. Levetiracetam.
C. Phenobarbital.
D. Clobazam.

A

Answer: B
This patient most likely has focal epilepsy, given the
description of his spells and the EEG. Ethosuximide
(Answer A) has a very narrow spectrum of generalized
nonmotor seizures, making it incorrect. Phenobarbital
(Answer C) has common or severe adverse effects,
making it less than optimal as initial pharmacotherapy.
Clobazam (Answer D) is indicated only for Lennox-
Gastaut syndrome. Levetiracetam (Answer B) is indicated
for monotherapy for focal seizures and has fewer
adverse effects than phenobarbital and clobazam.

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Q

B.V. is a 48-year-old woman brought to your ED for
the treatment of status epilepticus. Her blood glucose
is 50 mg/dL on fingerstick. Which medication
would be the best next treatment for B.V.?
A. Lorazepam.
B. Dextrose.
C. Thiamine.
D. Diazepam

A

Answer: C
With a blood glucose of less than 60 mg/dL, hypoglycemia
could be a cause of this patient’s status epilepticus.
Although lorazepam (Answer A) and diazepam
(Answer D) are appropriate for treating seizures not
caused by hypoglycemia, a possible hypoglycemic
episode must be treated first. Because the patient’s
nutritional status is unknown, she could be thiamine
deficient. Administering dextrose (Answer B) in the
face of thiamine deficiency could precipitate an encephalopathy.
Thiamine (Answer C) should be administered
before dextrose

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Q

J.H. is a 42-year-old man with focal-onset seizures
with loss of awareness for which he was prescribed
levetiracetam. He comes to the clinic with concerns
of agitation. He says his wife is also concerned
because he is very irritable and, at times,
depressed. Which best assesses J.H.’s condition?
A. Discontinue levetiracetam; he is having
adverse effects.
B. Increase the levetiracetam dose; he is having
focal seizures.
C. Continue levetiracetam; it is controlling his
seizures.
D. Obtain a levetiracetam serum concentration;
he is probably supratherapeutic.

A

Answer: A
Agitation and depression are common adverse effects
of levetiracetam. Because of the patient’s wife’s concerns
for his irritability and depression, it is probably
advisable to discontinue levetiracetam (Answer A) and
change to a different ASM. Increasing the dose (Answer
B) could worsen his symptoms, and his symptoms are
probably not the result of ongoing seizures. Continuing
levetiracetam (Answer C) might be an alternative, but
given that he and his spouse have concerns for adverse
effects, it is a less-than-optimal approach. No clear
correlation has been established between efficacy or
toxicity and levetiracetam concentrations (Answer D).
Therefore, a concentration would not help guide therapeutic
decisions.

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Q

Questions 4 and 5 pertain to the following case.
T.O. is a 68-year-old man who suddenly lost consciousness
at home. His partner calls 911, and emergency medical
technicians arrive within 10 minutes. According
to the medical record, he experienced slurred speech
and right arm weakness about 30 minutes before losing
consciousness. He is treated for hypertension.
4. Which test would be best before initiating pharmacotherapy
for T.O.?
A. Cerebral angiogram.
B. CT scan of head.
C. Coagulation panel.
D. Echocardiogram

A

Answer: B
The most critical test before initiating treatment for
stroke is head imaging. A CT scan of the head (Answer
B) allows the clinician to distinguish between an
ischemic stroke and a hemorrhagic stroke. A cerebral
angiogram (Answer A) may be helpful later to determine whether there is a lesion in the cerebral vasculature,
but it is not essential in the acute setting. A
coagulation panel (Answer C) is not necessary to determine
whether to initiate alteplase in the acute setting.
Similarly, an echocardiogram (Answer D) may be useful
in a patient’s diagnostic workup after a stroke, but it
is not necessary in the acute care setting.

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Q

T.O. is diagnosed with a major ischemic stroke and
treated with alteplase. He regains consciousness
and is transferred to rehabilitation. Which treatment
would be best for 3 months to prevent another
stroke?
A. Aspirin and clopidogrel.
B. Aspirin and dipyridamole.
C. Apixaban.
D. Warfarin.

A

Answer: A
A combination of aspirin and clopidogrel is indicated
for 90 days after a major ischemic stroke (Answer A).
A combination of aspirin and dipyridamole (Answer B)
is a possible treatment for long-term stroke prophylaxis
(after the 90-day DAPT with aspirin and clopidogrel).
Apixaban (Answer C) is only indicated for prophylaxis
in the setting of atrial fibrillation, which this patient
does not have. Warfarin (Answer D) is only indicated
for prophylaxis of stroke in atrial fibrillation or mechanical
mitral valve replacement.

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Q

Questions 6 and 7 pertain to the following case.
P.P. is a 75-year-old woman who was diagnosed with
Parkinson disease 8 years ago. During this visit to the
clinic, she notes that her movements are slower and she
feels stiffer. She has also experienced a worsening gait
with two or three falls in the past 6 months. Her writing
has also become small and illegible. She takes carbidopa/
levodopa 25/100 mg 2 tablets four times daily.
6. Which of P.P.’s symptoms would best be controlled
by pharmacotherapy?
A. Gait disturbances.
B. Falls.
C. Handwriting.
D. Rigidity.

A

Answer: D
Gait disturbances (Answer A), falls (Answer B), and
handwriting (Answer C) are not improved by use of
levodopa or a dopamine agonist. Rigidity (Answer D)
is improved with levodopa or a dopamine agonist.

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Q

P.P. notes that her symptoms seem worse before
her next dose of carbidopa/levodopa. Which agent
would best be added at this visit?
A. Istradefylline.
B. Entacapone.
C. Apomorphine.
D. Quetiapine.

A

Answer: B
This patient is experiencing wearing-off before the next
dose. A COMT inhibitor, entacapone (Answer B), slows
the degradation of dopamine in the synaptic cleft and
extends the effectiveness of levodopa. Istradefylline
(Answer A) is adenosine receptor antagonist that may
be used as an adjunct to carbidopa/levodopa and treats
off-episodes. Apomorphine (Answer C) is indicated
for on-off phenomenon but is not indicated for wearing-
off before the next dose. Quetiapine (Answer D) is
a preferred antipsychotic to manage hallucinations secondary
to Parkinson disease itself or adverse effects of
dopamine agonists.

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Q

W.S. is a 70-year-old man with newly diagnosed
Parkinson disease who is initiated on carbidopa/
levodopa. His symptoms are well controlled, but
he has concerns of nausea and vomiting. Which
intervention would be best to reduce his nausea
and vomiting?
A. Initiate promethazine.
B. Initiate metoclopramide.
C. Decrease carbidopa/levodopa.
D. Initiate trimethobenzamide.

A

Answer: D
Many medications used for nausea, including metoclopramide
(Answer B) and promethazine (Answer
A), are dopamine antagonists and potentially worsen
nausea and vomiting. Reducing carbidopa/levodopa
(Answer C) would likely worsen Parkinson symptoms.
Trimethobenzamide (Answer D) is a selective antagonist for the D2 receptor, making it less likely to
worsen Parkinson symptoms.

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Q

Questions 9 and 10 pertain to the following case.
R.M. is a 42-year-old man with headaches, which he
describes as a tight band around his head. The headaches
occur three or four times a week.
9. Which medication would be the best acute treatment
for R.M. to use for his headaches?
A. Naproxen.
B. Sumatriptan.
C. Dihydroergotamine.
D. Lithium.

A

Answer: A
This patient most likely has tension headaches, given
his description of the headaches. The most effective
medication for acute treatment of tension headaches
is naproxen (Answer A). Sumatriptan (Answer B)
and dihydroergotamine (Answer C) are indicated for
acute treatment of migraine-type headaches. Lithium
(Answer D) is only used to prevent cluster headaches.

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Q

R.M is requesting a preventive medication to help
reduce his headache frequency. Which agent would
be best to recommend?
A. Amitriptyline.
B. Valproate.
C. Topiramate.
D. Frovatriptan

A

Answer: A
This patient most likely has a tension-type headache.
Amitriptyline (Answer A) is effective for preventing
tension-type headaches. Valproate (Answer B) and
topiramate (Answer C) are not used to prevent tension-
type headaches. Frovatriptan (Answer D) is only
indicated for the acute treatment of migraine

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Q

Questions 11–13 pertain to the following case.
L.M. is a 43-year-old man diagnosed with relapsing-
remitting multiple sclerosis (MS) 2 years ago. He
has taken glatiramer acetate since then. However, his
exacerbations have not discernibly decreased. He has
spasticity in his legs, which has caused several falls
in the past month, and fatigue that worsens as the day
progresses.
11. Which medication would be best for L.M.’s MS?
A. Cyclophosphamide.
B. Methylprednisolone.
C. Azathioprine.
D. Fingolimod.

A

Answer: D
Fingolimod (Answer D) is the only choice with an FDA
indication for the treatment of MS. In addition, fingolimod
has the best clinical trial evidence of efficacy.
Methylprednisolone (Answer B) is used for acute MS
exacerbations. Cyclophosphamide (Answer A) and azathioprine
(Answer C) have been studied in progressive
forms of MS, but their data are not as robust as those
for fingolimod.

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Q

Which medication would be best for L.M.’s
spasticity?
A. Diazepam.
B. Baclofen.
C. Carisoprodol.
D. Metaxalone.

A

Answer: B
Treatment of spasticity in MS requires a centrally acting
agent. Of the choices, only diazepam (Answer A)
and baclofen (Answer B) are centrally acting. Because
of the significant fatigue and drowsiness that occur
with diazepam, baclofen is usually a first-line therapy.
Carisoprodol (Answer C) and metaxalone (Answer D)
are indicated for muscle spasms, but not spasticity

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Q

Which medication would be best for L.M.’s fatigue?
A. Propranolol.
B. Lamotrigine.
C. Amantadine.
D. Ropinirole.

A

Answer: C
Amantadine (Answer C) is used in MS for fatigue.
Propranolol (Answer A), lamotrigine (Answer B), and
ropinirole (Answer D) are not used in MS.

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Q

Questions 14 and 15 pertain to the following case.
B.T. is a 62-year-old man with obesity (weight 122 kg)
who comes to the clinic with concerns of burning in
the soles of his feet. These symptoms began about 3
months ago. They are worse at night and keep him from
sleeping. On examination, he has decreased sensation
in both feet up to the ankles bilaterally and good
strength throughout his feet and legs. His ankle reflexes
are decreased. He has hypertension treated with lisinopril
10 mg/day.
14. Which most likely caused B.T.’s pain and decreased
sensation?
A. Diabetic neuropathy.
B. Chronic inflammatory demyelinating
polyneuropathy.
C. Entrapped nerve.
D. Genetic neuropathy.

A

Answer: A
Diabetic neuropathy (Answer A) is the most common
cause of peripheral neuropathy and may occur even
before a patient is diagnosed with diabetes. Chronic
inflammatory demyelinating polyneuropathy (Answer B) and genetic neuropathy (Answer D) are much less
common, and symptoms are not consistent with this
presentation. An entrapped nerve (Answer C) would
typically be unilateral.

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Q

Which treatment would be best for B.T.’s symptoms?
A. Carbamazepine 600 mg at bedtime.
B. Lidocaine 5% patch applied to soles of feet at
bedtime and removed in the morning.
C. Acetaminophen 325 mg every 4 hours as
needed.
D. Valproate 250 mg twice daily.

A

Answer: B
Carbamazepine (Answer A) and valproate (Answer
D) are considered third-line medications for diabetic
neuropathy pain. Acetaminophen (Answer C) would
unlikely relieve symptoms. Lidocaine (Answer B)
would be best for initial treatment of the patient’s neuropathic
pain.

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Q

Patient Cases
Questions 1–3 pertain to the following case.
T.M. is a 23-year-old woman with newly diagnosed generalized motor myoclonic-type seizures. She is in good
health and takes oral contraceptives.
1. Which is the best medication for T.M.’s seizures?
A. Valproate.
B. Phenytoin.
C. Phenobarbital.
D. Levetiracetam

A

Answer: D
Generalized motor myoclonic-type seizures can be
treated in several ways; the best option in this case is
levetiracetam (Answer D), which is effective for generalized
motor myoclonic-type epilepsy and has much less
risk of teratogenic effects. Phenytoin (Answer B) and
phenobarbital (Answer C) are considered second-line
treatments for generalized motor myoclonic-type seizures
and can reduce the effectiveness of oral contraceptives.
Although valproate (Answer A) is effective
for generalized motor myoclonic-type seizures, it is
associated with several teratogenic effects. Because
this patient is a woman of childbearing potential, it is
advisable to avoid valproate even though she takes oral
contraceptives.

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Q

T.M. is concerned about the impact of levetiracetam on her oral contraceptives. Which response is best?
A. Levetiracetam does not alter the effectiveness of your oral contraceptives.
B. You should use alternative forms of birth control because levetiracetam decreases oral contraceptive
effectiveness.
C. You may have breakthrough bleeding, but the effectiveness of the oral contraceptive is not changed.
D. Oral contraceptives decrease the effectiveness of levetiracetam, so you need another form of birth control.

A

Answer: A
Interactions with oral contraceptives are a concern
with several ASMs. In these cases, alternative forms of
birth control (Answer B) may be necessary. Decreased
effectiveness of oral contraceptives may be associated
with breakthrough bleeding (Answer C). In addition,
oral contraceptives can alter the effectiveness of ASMs
(Answer D). However, no evidence supports that levetiracetam
alters oral contraceptive effectiveness or that
oral contraceptives change the effectiveness of levetiracetam,
making Answer A correct.

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Q

Three months later, T.M.’s seizures are reduced in frequency, but continue despite medication adherence and
maximized dosing. Which would be the best alternative?
A. Lamotrigine.
B. Rufinamide.
C. Cannabidiol.
D. Valproate

A

Answer: A
Rufinamide (Answer B) is not first line for treating
generalized motor myoclonic-type seizures; instead, it
is indicated for first-line treatment of Lennox-Gastaut
syndrome. Cannabidiol (Answer C) has only been
shown effective in Dravet syndrome and Lennox-
Gastaut syndrome. Valproate (Answer D) should be
avoided in this patient because of its teratogenic adverse
effects. Lamotrigine (Answer A) is a reasonable alternative
that is first line for treating generalized motor
myoclonic-type seizures and is not associated with an
increased risk of teratogenic adverse effects; however,
the potential for reduced oral contraceptive effectiveness
should be discussed.

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Q

J.G. is a 34-year-old patient who presents to the ED in status epilepticus. All of her laboratory values are normal.
Which medication is best to use first?
A. Valproate.
B. Lorazepam.
C. Phenytoin.
D. Phenobarbital.

A

Answer: B
Lorazepam (Answer B) is the drug of choice for status
epilepticus. Lorazepam is less lipophilic than diazepam
(Answer A); therefore, lorazepam does not redistribute from the CNS as quickly. Phenytoin (Answer C) and
phenobarbital (Answer D) should be held in reserve for
maintenance therapy or refractory status epilepticus.

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Q

S.R. is a 37-year-old patient who began taking phenytoin 100 mg 3 capsules orally at bedtime 6 months ago. He
has had several seizures since then, the most recent of which occurred 7 days ago. At that time, his phenytoin
serum concentration was 8 mcg/mL. The treating physician increased his phenytoin dose to 100 mg 3 capsules
orally twice daily. Today, which best represents his expected serum concentration?
A. 10 mcg/mL.
B. 14 mcg/mL.
C. 16 mcg/mL.
D. 24 mcg/mL

A

Answer: D
Phenytoin has nonlinear pharmacokinetics. A small
increase in dose may result in a large increase in serum
concentration. Therefore, without doing any calculations,
we can surmise that an increase from 300 mg/day
to 600 mg/day would more than double the serum concentration
(Answer D). Lower increases (Answers A–C)
would be unlikely with an increase in dose this large.

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Q

S.S. is a 7-year-old girl. Her teacher contacts the girl’s parents because of concern about the girl’s “daydreaming”
in class. After an evaluation, S.S. is diagnosed with generalized nonmotor (absence) seizures. Which
agent is best to treat this type of epilepsy?
A. Phenytoin.
B. Valproate.
C. Carbamazepine.
D. Ethosuximide.

A

Answer: D
Phenytoin (Answer A) and carbamazepine (Answer
C) can increase absence seizure frequency. Valproate
(Answer B), though an alternative, is less desirable
because of its adverse effect profile. Ethosuximide
(Answer D) is useful for absence seizures and had fewer
adverse effects than valproate in a randomized study.

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Q

J.B. is a 25-year-old man with a history of seizure disorder. He has been treated with carbamazepine for 1 year,
and his current carbamazepine concentration is 12 mcg/mL. Which adverse effect is J.B. most likely to have
with carbamazepine at this concentration?
A. Hepatotoxicity.
B. Acne.
C. Gingival hyperplasia.
D. Diplopia.

A

Answer: D
Although hepatotoxicity (Answer A) is a possible
adverse effect of carbamazepine, it is most likely to occur
within the first few months of starting carbamazepine.
Acne (Answer B) and gingival hyperplasia (Answer C)
are adverse effects associated with phenytoin. Diplopia
(Answer D) is a common adverse effect associated with
higher concentrations of carbamazepine.

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Q

M.G. has been prescribed levetiracetam. On which adverse effect is it best to counsel M.G.?
A. Hepatoxicity.
B. Renal stones.
C. Depression.
D. Word-finding difficulties.

A

Answer: C
Hepatoxicity (Answer A) is associated with several
ASMs but not with levetiracetam. Alopecia (Answer
D) is a common adverse effect of valproate. Depression
(Answer C) and agitation are common adverse effects
of levetiracetam. Zonisamide is associated with a 1%
increase in the risk of renal stones (Answer B).

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Q

Questions 9 and 10 pertain to the following case.
G.Z., a 26-year-old woman, presents with a 6-month history of “spells.” The spells are all the same, and all begin
with a feeling in the abdomen that is difficult for her to describe. This feeling rises toward the head. The patient
believes that she will then lose awareness. After a neurologic workup, she is diagnosed with focal seizures
evolving to a bilateral, convulsive seizure. The neurologist is considering initiating either carbamazepine or
oxcarbazepine.

Which is the most accurate comparison of carbamazepine and oxcarbazepine?

A. Oxcarbazepine causes more liver enzyme induction than carbamazepine.
B. Oxcarbazepine does not cause rash.
C. Oxcarbazepine does not cause hyponatremia.
D. Oxcarbazepine does not form an epoxide intermediate in its metabolism.

A

Answer: D
Carbamazepine forms an active epoxide intermediate
(carbamazepine-10,11-epoxide), whereas oxcarbazepine
does not (Answer D). Carbamazepine induces
more liver enzymes than oxcarbazepine (Answer A).
However, hyponatremia is more closely associated
with oxcarbazepine than with carbamazepine (Answer
C). Both carbamazepine and oxcarbazepine can cause
allergic rashes (Answer B).

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10. When you see G.Z. 6 months later for a follow-up, she tells you she is about 6 weeks pregnant. She has had no seizures since starting oxcarbazepine. Which strategy is best for G.Z.? A. Discontinue her seizure medication immediately. B. Change her seizure medication to topiramate. C. Continue her seizure medication. D. Change her seizure medication to lamotrigine.

10. Answer: C Immediate discontinuation of oxcarbazepine (Answer A) would likely increase seizures. Topiramate (Answer B) is associated with an increased risk of teratogenic adverse effects. Lamotrigine (Answer D) is considered safe during pregnancy, but changing medications increases the risk of seizures. In addition, lamotrigine pharmacokinetics change during pregnancy, complicating its management. Continuing the patient’s current medication (Answer C) is the best approach during pregnancy.

Questions 11–15 pertain to the following case. L.R. is a 78-year-old woman who presents to the ED for symptoms of right-sided paralysis. She states these symptoms began about 6 hours ago and have not improved. She also has hypertension, breast cancer, diabetes, minimal cognitive impairment, and osteoarthritis. L.R. is diagnosed with a minor stroke by the neurology team. 11. Which is the most accurate list of L.R.’s risk factors for stroke? A. Breast cancer, age, osteoarthritis. B. Sex, diabetes, osteoarthritis. C. Minimal cognitive impairment, diabetes, age, sex. D. Age, diabetes, hypertension.

11. Answer: D Nonmodifiable risk factors for stroke include age, race, and male sex. Somewhat modifiable risk factors include hypercholesterolemia and diabetes. Modifiable stroke risk factors include hypertension, smoking, and atrial fibrillation. Less well-documented risk factors include obesity, physical inactivity, alcohol abuse, hyperhomocystinemia, hypercoagulability, hormone replacement therapy, and oral contraceptives. Minimal cognitive impairment (Answer C) and osteoarthritis (Answers A and B) are not risk factors for stroke. Answer D is the only option that includes only risk factors for stroke.

12. Which best describes whether L.R. is a candidate for tissue plasminogen activator (Alteplase) for the treatment of stroke? A. Yes. B. No, because of advanced age. C. No, her stroke symptoms began too long ago. D. No, her breast cancer is a contraindication for tissue plasminogen activator.

12. Answer: C There are many contraindications to administering tissue plasminogen activator for stroke, mainly focused on bleeding risk. There is no upper limit on age (Answer B). Breast cancer (Answer D) is not a contraindication for tissue plasminogen activator. The patient’s symptoms began 6 hours ago, placing her outside the window for alteplase use (Answer C is correct; Answer A is incorrect).

13. L.R. previously took no home medications. Which is the best treatment at this time for her? A. Metformin and aspirin. B. Celecoxib and clopidogrel. C. Aspirin and clopidogrel. D. Warfarin.

13. Answer: C Warfarin (Answer D) is only indicated for stroke prevention with atrial fibrillation. Other than modifying a partly modifiable risk factor for stroke, metformin (Answer A) has no benefit in preventing stroke. Celecoxib (Answer B) also has no benefit in preventing stroke and, according to some studies, may increase the risk of stroke. Aspirin and clopidogrel (Answer C) should be used together for 21 days after a minor acute stroke to reduce the risk of another stroke.

14. L.R. presents to her community pharmacy to pick up her medication refills (lisinopril, aspirin, clopidogrel, atorvastatin) 2 months after her discharge from the hospital. Which best assesses her dual antiplatelet therapy (DAPT)? A. Appropriate, continue for 90 days after stroke. B. Appropriate, continue as chronic therapy. C. Inappropriate, single antiplatelet therapy should be initiated for 90 days. D. Inappropriate, single antiplatelet therapy should be initiated indefinitely.

14. Answer: D This patient was diagnosed with a minor stroke, according to the neurology team. Dual antiplatelet therapy should be initiated within 24 hours of a minor stroke and continued for 21 days. After the 21 days of DAPT, the patient should be transitioned to single antiplatelet therapy, which should be continued indefinitely. Answer A is incorrect; DAPT should be continued for 21 days, not 90 days, after a (minor) stroke. Answer B is incorrect; DAPT should not be continued as chronic therapy because the patient has been receiving it for 60 days, which exceeds the 21-day recommendation. Single antiplatelet therapy should be continued indefinitely, not just for 90 days, making Answer C incorrect and Answer D correct.

15. L.S. is a 42-year-old woman with a medical history of hypertension, type 2 diabetes, renal failure, and mitral valve replacement. She presents to the anticoagulation clinic for her initial visit. Which best reflects her target INR? A. 1.5. B. 2.0. C. 2.5. D. 3.0.

15. Answer: D With a mitral valve replacement, the target INR is 2.5– 3.5, making 3 (Answer D) an optimal target. An INR of 1.5 (Answer A) or 2 (Answer B) is too low for a valve replacement. An INR of 2.5 (Answer C) is at the bottom of the acceptable target range, making it difficult to consistently keep her INR in the range.

Questions 16 and 17 pertain to the following case. L.T. takes carbidopa/levodopa 25 mg/100 mg orally four times daily and trihexyphenidyl 2 mg orally three times daily for Parkinson disease. L.T.’s wife reports that his movements are very slow and that he is having trouble walking. 16. Given these symptoms, which change seems most reasonable? A. Increase carbidopa/levodopa, discontinue trihexyphenidyl. B. Continue carbidopa/levodopa, increase trihexyphenidyl. C. Decrease carbidopa/levodopa, continue trihexyphenidyl. D. Decrease carbidopa/levodopa, increase trihexyphenidyl

16. Answer: A Anticholinergic drugs like trihexyphenidyl only control tremor – not other symptoms of Parkinson disease. Increasing the trihexyphenidyl dose (Answers B and D) would not improve control of his symptoms and would increase anticholinergic adverse effects. Decreasing the carbidopa/levodopa dose (Answer C) would worsen his Parkinson disease symptoms. Increasing the carbidopa/ levodopa dose and discontinuing trihexyphenidyl (Answer A) should improve all of his symptoms and reduce any anticholinergic adverse effects.

17. Six months later, L.T. returns to the clinic concerned that his carbidopa/levodopa dose is wearing off before his next dose is due, because his tremor and slow movements are worse before the next dose of carbidopa/ levodopa. Which recommendation is best? A. Increase the carbidopa/levodopa dose. B. Decrease the carbidopa/levodopa dose. C. Increase the dosing interval. D. Decrease the dosing interval.

17. Answer: D Wearing-off phenomenon is the return of Parkinson disease symptoms before the next dose. This problem can be resolved by administering doses more often (Answer D), administering the controlled-release formulation of carbidopa/levodopa, or adding a COMT inhibitor. Increasing the dosing interval (Answer C) means that doses are administered further apart. Increasing the dose (Answer A) would not address wearing-off at the end of a dosing interval and would place the patient at risk of developing dyskinesia. Decreasing the dose (Answer B) would cause the patient’s Parkinson symptoms to worsen.

18. P.J. is a 57-year-old man with an 8-year history of Parkinson disease. His current medications include carbidopa/ levodopa 50 mg/200 mg orally four times daily, entacapone 200 mg orally four times daily, and amantadine 100 mg three times daily. He presents to the clinic with concerns of reddish orange urine. He fears he has blood in his urine. Which most likely caused this condition? A. Carbidopa/levodopa. B. Entacapone. C. Amantadine. D. Hemorrhagic cystitis.

18. Answer: B Entacapone (Answer B) can cause a reddish orange discoloration of the urine. Amantadine (Answer C) can cause a reddish brown skin discoloration, but not changes in the urine. Carbidopa/levodopa (Answer A) does not cause changes in the urine. Cystitis (Answer D) is a possibility, but entacapone more likely caused the change in urine color.

19. L.L. is a 47-year-old man with Parkinson disease. He takes carbidopa/levodopa 50 mg/200 mg orally four times daily. His wife states that he cannot sit still during the day. He is constantly moving, and she fears his disease is worsening. Which is the best therapy for L.L.? A. Add ropinirole. B. Add selegiline. C. Increase the carbidopa/levodopa dose. D. Decrease the carbidopa/levodopa dose.

19. Answer: D Ropinirole (Answer A) helps with the initial treatment of Parkinson disease, but adding it to the patient’s current regimen without adjusting the carbidopa/levodopa dose would worsen his dyskinesia. Selegiline (Answer B) would not address his dyskinesia and could make it worse by decreasing the breakdown of levodopa. Increasing the carbidopa/levodopa dose (Answer C) would make his dyskinesia worse. Decreasing the carbidopa/ levodopa dose (Answer D) will improve the dyskinesia.

20. C.A. is a 70-year-old man with tremors in his right hand that have progressively worsened for the past 6 months. He has difficulty walking. He also has backaches and no longer plays golf. In addition, he is losing his sense of taste. His wife notes that he is moving more slowly and that his handwriting has deteriorated. He is diagnosed with Parkinson disease. Which is the best treatment for C.A.? A. Trihexyphenidyl. B. Apomorphine. C. Carbidopa/levodopa. D. Istradefylline

20. Answer: C Trihexyphenidyl (Answer A) is only effective for tremors in Parkinson disease and has anticholinergic adverse effects. In this patient, it would not treat the other symptoms of the disease, and anticholinergic adverse effects are not advisable in an older individual. Carbidopa/ levodopa (Answer C) is efficacious as monotherapy for symptomatic Parkinson disease. Istradefylline (Answer D) is an adjunct to carbidopa/levodopa. Apomorphine (Answer B) is for the acute treatment of off-episodes and not clinically useful for symptomatic Parkinson disease as monotherapy.

21. M.R., a 29-year-old woman, has throbbing right-sided headaches. She experiences nausea, phonophobia, and photophobia with these headaches but no aura. She usually has headaches twice a month. She has hypertension and morbid obesity. She takes hydrochlorothiazide 25 mg/day orally for hypertension, which is the only medication she is taking. Which medication is best for prophylaxis of her headaches? A. Propranolol. B. Indomethacin. C. Topiramate. D. Sumatriptan

21. Answer: A A β-blocker (Answer A) is a good choice for a patient with coexisting hypertension. Indomethacin (Answer B) can be used for migraine, but it is held in reserve because of serious adverse effects. Although topiramate (Answer C) might decrease the patient’s weight, it has an increased risk of teratogenic adverse effects. Sumatriptan (Answer D) is for the acute treatment of migraine headaches, not for prophylaxis.

22. S.R. is a 54-year-old businessman with squeezing, band-like headaches that occur three or four times weekly. He rates the pain of these headaches as 7/10 and finds acetaminophen, aspirin, ibuprofen, naproxen, ketoprofen, and piroxicam only partly effective. He wants to take a prophylactic drug to prevent his headache disorder. Which medication would be best for prophylaxis of his headaches? A. Propranolol. B. Topiramate. C. Amitriptyline. D. Rizatriptan.

22. Answer: C Amitriptyline (Answer C) is effective as prophylaxis for tension headaches. Propranolol (Answer A) and topiramate (Answer B) are usually used for migraine headache prophylaxis. Rizatriptan (Answer D) is an acute treatment for migraine headaches

23. D.S. is a 49-year-old male computer programmer who describes piercing right-eye pain and lacrimation several times a day for 2–3 days in a row. He will have no episodes for 2–3 weeks but will then have recurrent episodes. In the office, he receives oxygen by nasal cannula during an episode, and his pain is relieved. Which medication would be best for prophylaxis of his headaches? A. Atenolol. B. Valproate. C. Nortriptyline. D. Lithium.

23. Answer: D Lithium (Answer D) is a prophylactic agent for cluster headaches. Atenolol (Answer A) and valproate (Answer B) are usually used for migraine headache prophylaxis. Nortriptyline (Answer C) is useful for migraine and tension headaches.

24. M.K. is a 44-year-old woman with right-sided headaches of moderate intensity that are accompanied by severe nausea and vomiting. Which medication would be best for M.K.’s migraine headaches? A. Almotriptan. B. Naratriptan. C. Promethazine. D. Sumatriptan.

24. Answer: D Sumatriptan (Answer D) is available as both an injectable and a nasal spray and would be appropriate to use in a patient with severe nausea and vomiting. Almotriptan (Answer A) and naratriptan (Answer B) only come in oral dosage forms and would not be optimal in the face of nausea and vomiting. Promethazine (Answer C) might reduce nausea and vomiting but would not treat the patient’s migraine headache

25. T.C. is a 30-year-old woman with migraine headaches. Sumatriptan 100 mg provides immediate relief. However, about 2 hours later, her headache symptoms return. Which would be best for her? A. Rizatriptan 5 mg. B. Frovatriptan 2.5 mg. C. Naproxen 250 mg. D. Topiramate 25 mg

25. Answer: B Topiramate (Answer D) is used as a prophylactic drug and not in the acute treatment of a migraine. Naproxen (Answer C) would be less likely to relieve her headache without being combined with a triptan. Rizatriptan (Answer A) has a short half-life, making it less effective 2 hours later. Frovatriptan (Answer B) has a longer half-life, making it more likely to prevent the headache from returning 2 hours later.

Questions 26–28 pertain to the following case: S.F. is a 36-year-old woman with a history of MS. This morning, her left arm became progressively weaker over about 3 hours. She was previously healthy except for a broken radius when she was 13 years old and a case of optic neuritis when she was 25. Her current medications include metoprolol 100 mg orally twice daily and fluoxetine 10 mg orally daily. 26. Which would be best for treating S.F.’s exacerbation? A. Interferon beta-1a. B. Glatiramer acetate. C. Methylprednisolone. D. Fingolimod.

26. Answer: C Methylprednisolone (Answer C) is the only option used for acute exacerbations. Interferon beta-1a (Answer A), glatiramer acetate (Answer B), and fingolimod (Answer D) are all used as disease-modifying therapies

27. Which would be best for S.F. to prevent further exacerbations? A. Methylprednisolone. B. Baclofen. C. Glatiramer acetate. D. No treatment.

27. Answer: C Glatiramer acetate (Answer C) is an appropriate initial choice for disease-modifying therapy. Methylprednisolone (Answer A) is only for exacerbations. Baclofen (Answer B) is only for spasticity and does not have disease-modifying properties. Providing no treatment (Answer D) would be unacceptable because of the patient’s many episodes of exacerbations.

28. S.F. elects to start fingolimod. Which would be best to monitor every 6 months while she is taking fingolimod? A. ECG. B. Sodium. C. Pulmonary function tests. D. Renal function tests.

28. Answer: A Fingolimod (Answer A) is associated with cardiac arrhythmias, and the ECG should be monitored at least every 6 months. Sodium (Answer B), pulmonary function tests (Answer C), and renal function tests (Answer D) do not need to be routinely monitored with fingolimod.

29. B.B. is a 33-year-old woman with recently diagnosed MS. Her neurologist wants you to discuss with her the potential medications to prevent exacerbations. During the discussion, you find that she and her husband are planning to have a child in the next few years and that she is frightened of needles. Which would be best for B.B.? A. Glatiramer acetate. B. Mitoxantrone. C. Teriflunomide. D. Dimethyl fumarate.

29. Answer: D Glatiramer (Answer A) is not the best option because the patient is frightened of needles and glatiramer is an injectable; also, glatiramer should be avoided in pregnancy, if possible. Mitoxantrone (Answer B) has significant toxicities and is contraindicated in pregnancy. Teriflunomide (Answer C) is also contraindicated in pregnancy. Dimethyl fumarate (Answer D) is a pregnancy category C drug. However, this patient should carefully plan her conception and can discontinue the medication before pregnancy.

Questions 30 and 31 pertain to the following case. S.B. is a 55-year-old man referred to a neurologist for numbness, burning, and tingling in his feet that have progressively worsened over the past year. On neurologic examination, he has decreased sensations bilaterally to the mid-calf. He takes no medications except for nonprescription analgesics as needed for pain. His BMI is 32 kg/m2. 30. Which laboratory test would best determine the cause of S.B.’s neuropathy? A. Potassium. B. A1C. C. Serum creatinine. D. WBC.

30. Answer: B The most likely cause of peripheral neuropathy in this patient is diabetes, even if this was not previously diagnosed. Therefore, A1C (Answer B) is the most useful laboratory value for determining the potential cause. Potassium (Answer A), serum creatinine (Answer C), and WBC (Answer D) do not help determine the cause of neuropathy.

31. Which therapy would be best for S.B.? A. Naproxen. B. Tramadol. C. Nortriptyline. D. Prednisone.

31. Answer: C Naproxen (Answer A) would unlikely be beneficial because the patient has been taking nonprescription analgesics without symptom relief. Although tramadol (Answer B) is a possibility, it is usually considered second line for peripheral neuropathy. Prednisone (Answer D) is not typically used for the initial treatment of neuropathy. Prednisone can be used in very specific immunologic neuropathies, but these are unlikely in this scenario. Nortriptyline (Answer C) is considered a first-line treatment for peripheral neuropathy. Given that the patient has not previously been treated, it is the best initial treatment.

32. A meta-analysis of treatments for neuropathic pain included data from 26 clinical trials (MedGenMed 2007;9:36). The results of the review included the following data. Treatment No. Needed to Treat Tricyclic antidepressants 2.1 SNRIs 5.1 SSRIs 7 Given these data, which would be most effective for neuropathic pain? A. Duloxetine. B. Sertraline. C. Amitriptyline. D. Venlafaxine

32. Answer: C Number needed to treat (NNT) is an estimate of the number of patients who would need to receive treatment for one patient to benefit. Therefore, the lower the NNT, the more likely a treatment is to be effective. Tricyclic antidepressants, including amitriptyline (Answer C), have the lowest NNT value in this comparison, so they are most likely to be effective. Duloxetine (Answer A) and venlafaxine (Answer D) are less likely to effective. Sertraline (Answer B) is the least likely to be effective

# EPILEPSY Benzodiazepines

Benzodiazepines i. Mechanism of action: Augment γ-aminobutyric acid (GABA)-mediated chloride influx ii. Tolerance may develop: Usually used as adjunctive, short-term therapy iii. Most commonly used agents: Clorazepate (Tranxene), clobazam (Onfi, Sympazan), clonazepam (Klonopin), diazepam (Valium), and lorazepam (Ativan) iv. All benzodiazepines are controlled substances, scheduled as C-IV. v. For acute repetitive seizures: Intranasal midazolam (Nayzilam), intranasal diazepam (Valtoco), rectal diazepam (Diastat) vi. Nonepileptic indications: Clorazepate (anxiety disorders, anxiety), clonazepam (panic disorder with or without agoraphobia), lorazepam (anxiety disorders, anxiety, alcohol withdrawal)

Brivaracetam (Briviact)

i. Mechanism of action: Unknown mechanism, but has high affinity for synaptic vesicle protein 2A ii. Adverse effects: Somnolence, sedation, dizziness, fatigue iii. Drug interactions: Carbamazepine, phenobarbital, phenytoin

Cannabidiol (Epidiolex)

i. The only FDA-approved cannabis product for epilepsy ii. Approved for seizures caused by Dravet syndrome, tuberous sclerosis, and Lennox-Gastaut syndrome iii. Adverse effects: Sedation, drowsiness, diarrhea, intestinal cramping, increased liver transaminase (11% of patients); cannabidiol for 3% of patients is discontinued because of increased liver function tests iv. Metabolized by CYP2C19 and CYP3A4 v. Inhibitor of UGT1A9, UGT2B7, CYP2C8, CYP2C9, CYP2C19 vi. Possible inhibitor of CYP1A2, CYP2B6 vii. Inhibits metabolism of desmethylclobazam, the active metabolite of clobazam viii. Increased hepatotoxicity with concomitant valproate ix. Maintenance dose: 10–20 mg/kg/day in two divided doses; initiate with 5 mg/kg/day in two divided doses and titrate to optimal dose

Carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Teril)

i)Mechanism of action: Fast sodium channel blocker ii. Pharmacokinetics: Enzyme inducer, autoinduction iii. Adverse effects: Rash (occurs after a delay of 2–8 weeks), syndrome of inappropriate antidiuretic hormone release, aplastic anemia, thrombocytopenia, anemia, leukopenia, hyponatremia iv. Extended-release tablets (Tegretol XR) 100, 200, and 400 mg; extended-release capsules (Carbatrol) 100, 200, and 300 mg available. Dosing is still twice daily. Do not crush or chew. Extended-release capsules (Carbatrol) can be opened and sprinkled on food. Ghost tablets can occur in the stool with the extended-release tablets (Tegretol XR). v. Patients with the HLA-B*1502 allele have a 10-fold elevated risk of Stevens-Johnson syndrome. (a) Testing is recommended for Asian populations (including Asian Indian populations). (b) More than 15% of populations in Hong Kong, Malaysia, the Philippines, and Thailand have this allele. vi. Patients with the HLA-A*3101 allele have a 12-fold elevated risk of hypersensitivity syndrome and a 3-fold elevated risk of maculopapular exanthema. (a) Prevalence of this allele is 2%–5% in northern European populations and 9.1% in Japanese populations. (b) No recommendations have been issued for testing for this allele. vii. Nonepileptic indication: Trigeminal neuralgia

Cenobamate (Xcopri)

i. Mechanism of action: Inhibits voltage-gated sodium channels, modulates GABA receptors ii. Titrate slowly because of DRESS (drug rash with eosinophilia and systemic symptoms). iii. Contraindications: Familial short QT syndrome iv. Adjust dosing with renal function. v. CYP3A4 inducer; CYP2C19 inhibitor vi. Schedule V drug

Eslicarbazepine acetate (Aptiom)

i. Mechanism of action: Fast sodium channel blocker ii. Prodrug for eslicarbazepine, with active metabolites; R-licarbazepine 5%, oxcarbazepine 1% iii. Adverse effects: Similar to those of carbamazepine; possibly reduced risk of rash, aplastic anemia, thrombocytopenia, and leukopenia iv. Adjust dose if CrCl is less than 50 mL/minute/1.73 m2.

Ethosuximide (Zarontin)

i. Mechanism of action: T-type calcium current blocker ii. Useful only for absence seizures iii. Adverse effects: Anorexia, gastric upset, nausea, vomiting, epigastric/abdominal pain, drowsiness, leukopenia, agranulocytosis, pancytopenia

Felbamate (Felbatol)

i. Mechanism of action: Blocks glycine site on N-methyl-d-aspartate receptor ii. Serious adverse effects: Hepatotoxicity, aplastic anemia. Patient or guardian must sign consent form. iii. Uses: Only when seizures are severe and refractory to other medications and when the benefit clearly outweighs the potential adverse effects

Fenfluramine (Fintepla)

i. Mechanism of action for seizures: Unknown ii. Indication: Seizures caused by Dravet syndrome in individuals older than 2 years iii. Warnings: Valvular heart disease, pulmonary arterial hypertension iv. Only available through a Risk Evaluation and Mitigation Strategies (REMS) program v. Increased risk of serotonin syndrome when used in combination with other serotonergic agents

Fosphenytoin (Cerebyx)

i. Mechanism of action: Prodrug for phenytoin; fast sodium channel blocker ii. Uses: Parenteral formulation for loading or maintenance dosing in place of phenytoin; status epilepticus iii. Pharmacokinetics: Enzyme inducer, nonlinear kinetics iv. Dosing: Phenytoin equivalents (PE) (1.5 mg of fosphenytoin is equivalent to 1 mg of phenytoin sodium or 1 PE) are used. Loading dose: 10–20 mg of PE/kg intravenous or intramuscular dosing is appropriate. Maintenance dosage: Begin with 4–6 mg PE/kg/day in divided doses after administration of the loading dose. v. Adverse effects: Hypotension, perianal itching, other adverse effects of phenytoin vi. Advantages over phenytoin (a) Intramuscular or intravenous dosing (b) Phlebitis is minimized. (c) Infusion can be up to 150 mg PE per minute. In status epilepticus, infusion should be at 100–150 mg PE per minute. Maximum infusion rate is not to exceed 150 mg PE per minute because of the risk of severe hypotension and cardiac arrhythmias. (d) Can deliver in normal saline solution or 5% dextrose in water injection

Gabapentin (Neurontin)

i. Mechanism of action: Inhibition of α2δ subunit of voltage-dependent calcium channels ii. Pharmacokinetics: Not metabolized, eliminated renally; adjustments may be necessary for renal dysfunction and hemodialysis iii. Nonepileptic indication: Postherpetic neuralgia pain iv. Doses often exceed product information maximum of 3600 mg/day. v. Extended-release tablets (Gralise) 300 and 600 mg are available. Their indication is for postherpetic neuralgia, not epilepsy. vi. Gabapentin enacarbil (Horizant) extended-release tablets 300 and 600 mg are available. This is a prodrug for gabapentin and is indicated for postherpetic neuralgia and restless legs syndrome, not epilepsy. vii. Increased risk of sedation and respiratory depression when used in combination with other sedating medications or opioids

Ganaxolone (Ztalmy)

i. Indicated for the treatment of seizures associated with cyclin-dependent kinase-like deficiency disorder in patients 2 years and older ii. Mechanism of action: Positive modulation of the GABAA receptor in the CNS iii. Dosage form: Oral suspension 50 mg/mL iv. Dosing: Orally three times daily with food, titrated slowly (a) Dosage for patients weighing 28 kg or less: (1) The starting dosage is 6 mg/kg three times daily (18 mg/kg/day) for days 1–7; then: (2) 11 mg/kg three times daily (33 mg/kg/day) for days 8–14; then (3) 16 mg/kg three times daily (48 mg/kg/day) for days 15–21; then (4) Maximum dosage is 21 mg/kg three times daily (63 mg/kg/daily) on day 22 to ongoing. (b) Dosage for patients weighing over 28 kg: (1) The starting dosage is 150 mg three times daily (450 mg daily) for days 1–7; then (2) 300 mg three times daily (900 mg daily) for days 8–14; then (3) 450 mg three times daily (1350 mg daily) for days 15–21; then (4) Maximum dosage is 600 mg three times daily (1800 mg daily) on day 22 to ongoing. v. Adverse reactions: Somnolence, pyrexia, salivary hypersecretion, and seasonal allergy vi. Controlled substance scheduled C-V because of euphoric effects vii. Drug interactions: CYP3A4 inducers will decrease ganaxolone exposure. It is recommended to avoid concomitant use with strong or moderate CYP3A4 inducers; if unavoidable, consider a dosage increase, but do not exceed the maximum recommended dosage.

Lacosamide (Vimpat)

i. Mechanism of action: Slow sodium channel blocker ii. Maximum dose is 300 mg/day with a CrCl of 30 mL/minute/1.73 m2 or less or with mild to moderate hepatic impairment. iii. Adverse effects: PR interval prolongation or first-degree atrioventricular block; baseline and steady-state ECG recommended in patients with known cardiac conduction problems, taking medications known to induce PR interval prolongation, or with severe cardiac disease iv. Controlled substance scheduled C-V because of euphoric effects v. Parenteral formulation: Has an FDA indication only for replacement of oral formulation; however, may be used for status epilepticus

Lamotrigine (Lamictal)

i. Mechanism of action: Decreases glutamate and aspartate release, delays repetitive firing of neurons, blocks fast sodium channels ii. Adverse effects: Rash is a primary concern because of concern for progression to Stevens- Johnson syndrome or toxic epidermal necrolysis; lamotrigine must be titrated slowly to avoid a rash. iii. Valproic acid decreases lamotrigine metabolism (increases the serum concentration of lamotrigine); this interaction requires lower starting and final doses. iv. Estrogen-containing oral contraceptives increase lamotrigine clearance, so twice the amount of lamotrigine may be necessary. Lamotrigine toxicity has been reported during the end of placebo week of oral contraceptive use. v. Extended-release tablets (Lamictal XR) are available (25 mg, 50 mg, 100 mg, 200 mg, 250 mg, 300 mg). vi. Nonepileptic indications: Maintenance treatment of type I bipolar disorder

Levetiracetam (Keppra)

i. Mechanism of action: May prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity through binding at SV2A receptor ii. Pharmacokinetics: Not metabolized extensively; adjust dose in renal dysfunction; no drug interactions with other seizure medications iii. Adverse effects: Drowsiness, behavioral changes, depression, agitation, and coordination difficulties iv. Parenteral use: Currently FDA indicated only for replacement of oral dosing; however, may be used for status epilepticus v. Extended-release tablets (500 mg, 750 mg) are available for once-daily dosing.

Oxcarbazepine (Trileptal)

i. Mechanism of action: Fast sodium channel blocker ii. Pharmacokinetics: Active metabolite 10-monohydroxy oxcarbazepine; enzyme inducer, no autoinduction iii. Drug interactions: Enzyme inducer, decreases effectiveness of hormonal contraceptives iv. Adverse effects: Hyponatremia more common than with carbamazepine (increased dose and advanced age increase risk of hyponatremia); blood dyscrasias less common than with carbamazepine; 25%–30% of patients with hypersensitivity to carbamazepine will have hypersensitivity to oxcarbazepine; rash v. Extended-release tablets (Oxtellar XR) are available (150 mg, 300 mg, 600 mg).

Perampanel (Fycompa)

i. Mechanism of action: Noncompetitive antagonist of the inotropic α-amino-3-hydroxy- 5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor ii. Pharmacokinetics: 95%–96% protein bound to albumin and α1-acid glycoprotein; metabolized by CYP3A4 and CYP3A5; 105-hour half-life iii. Adverse effects: Neuropsychiatric effects (irritability, aggression, anger, anxiety), dizziness, gait disturbance, weight gain iv. Perampanel is a schedule III controlled substance

Phenobarbital (Luminal)

i. Mechanism of action: Increases GABA-mediated chloride influx ii. Pharmacokinetics: Enzyme inducer iii. Adverse effects: Hyperactivity, cognitive impairment iv. Phenobarbital is a schedule IV controlled substance. v. Nonepileptic use: Anxiety, severe alcohol withdrawal

Phenytoin (Dilantin, Phenytek)

i. Mechanism of action: Fast sodium channel blocker ii. Pharmacokinetics: Enzyme inducer, nonlinear kinetics Administration considerations (a) Intravenous formulation: Very basic product. Phlebitis and extravasation are concerns; hypotension; maximal infusion rate of 50 mg/minute because of risk of cardiac arrhythmias and hypotension. Can prepare only in normal saline solution (b) Oral suspension: Must be shaken well; adheres to feeding tubes and is bound by enteral nutrition products iv. Dose-related adverse effects: Nystagmus, ataxia, drowsiness, cognitive impairment v. Non–dose-related adverse effects: Gingival hyperplasia, hirsutism, acne, rash, hepatotoxicity, coarsening of facial features

Pregabalin (Lyrica)

i. Mechanism of action: Inhibition of α2δ subunit of voltage-dependent calcium channels ii. Pharmacokinetics: Not metabolized, renally excreted; reduce dose in renal dysfunction iii. Adverse effects: Drowsiness, blurred vision, weight gain, edema, angioedema, CK elevations (three reports of rhabdomyolysis), rash iv. Schedule V controlled substance: Insomnia, nausea, headache, diarrhea reported after abrupt discontinuation; gradually discontinue over at least 1 week v. Nonepileptic indications: Neuropathic pain associated with diabetic neuropathy, postherpetic neuralgia, spinal cord injury, generalized anxiety disorder, and fibromyalgia vi. Increased risk of sedation and respiratory depression when used in combination with other sedating medications or opioids

# first choice only FOCAL EPILEPSY

Carbamazepine Gabapentin Lacosamide Lamotrigine Levetiracetam Oxcarbazepine Topiramate Zonisamide

# first choice only GENERALIZED MOTOR

Carbamazepine Lamotrigine Levetiracetam Oxcarbazepine Topiramate Valproic acid

# first line only Absence seizure

Ethosuximide Vaproic acid

Atonic seizure

Clonazepam Valproic acid

Myoclonic seizure

Topiramate Valproic acid

Infantile spasm

Valproic acid

# first line only Dravet's syndrome

Levetiracetam

Lennox- Gastaut Syndrome

Clobazam Clonazepam Lamotrigine Rufinamide

Primidone (Mysoline)

i. Mechanism of action: Increases GABA-mediated chloride influx ii. Metabolized to phenobarbital and phenylethylmalonamide iii. Adverse effects: Sedation, drowsiness, ataxia, rash iv. Primidone, phenobarbital, and phenylethylmalonamide all have antiepileptic action. v. Pharmacokinetics: Enzyme inducer vi. Also used for essential tremor

Rufinamide (Banzel)

i. Mechanism of action: Fast sodium channel blocker ii. Pharmacokinetics: Absorption increased by food (should be administered with food); metabolized by hydrolysis rather than through CYP enzymes iii. Adverse effects: Headache, dizziness, fatigue, somnolence, nausea iv. Decreases concentrations of ethinyl estradiol and norethindrone v. Has an FDA indication only for Lennox-Gastaut syndrome vi. Slightly shortens the QT interval and therefore should not be used in patients with familial short QT syndrome vii. Available as an oral solution

Stiripentol (Diacomit)

i. Indicated for Dravet syndrome in combination with clobazam ii. Dose: 50 mg/kg/day in two or three divided doses iii. Adverse effects: Somnolence, decreased appetite, agitation, ataxia, weight loss, hypotonia, nausea, tremor, dysarthria, insomnia iv. Pharmacokinetics: Inhibits CYP 1A2, 2C19, 2D6, and 3A4

Tiagabine (Gabitril)

i. Mechanism of action: Blocks GABA reuptake in the presynaptic neuron ii. Associated with new-onset seizures and status epilepticus in patients without epilepsy iii. Adverse effects: Dizziness, asthenia, somnolence, nervousness, tremor, diarrhea

Topiramate (Topamax)

i. Mechanism of action: Fast sodium channel blocker, enhances GABA activity and antagonizes AMPA/kainate activity, weak carbonic anhydrase inhibitor ii. Pharmacokinetics: Not extensively metabolized, eliminated in urine iii. Adverse effects: Drowsiness, paresthesias, psychomotor slowing (titrate slowly), weight loss, nephrolithiasis, acute angle-closure glaucoma, metabolic acidosis, hyperthermia (associated with decreased perspiration, or oligohidrosis), and decreased cognition, including word-finding difficulties iv. Extended-release formulations (Trokendi XR, Qudexy XR) v. Nonepileptic indication: Prophylaxis of migraine headaches, weight loss secondary to antipsychotic use

Valproic acid

Valproic acid, divalproex sodium, valproate (Depacon, Depakene, Depakote, Stavzor) i. Mechanism of action: Blocks T-type calcium currents, blocks sodium channels, increases GABA production ii. Pharmacokinetics: Enzyme inhibitor ii. Parenteral use: Has FDA indication only for replacement of oral dosing; however, sometimes used for status epilepticus, especially if absence status epilepticus iv. Adverse effects: Hepatotoxicity, nausea and vomiting, weight gain, interference with platelet aggregation, pancreatitis, alopecia, tremor Available in immediate-release (valproic acid [Depakene]) capsules for three- or four-timesdaily dosing; delayed-release (enteric coated) (divalproex sodium [Depakote], valproic acid [Stavzor]) capsules and tablets for twice-daily dosing (if patient is taking an enzyme inducer, agent is dosed more often); and extended-release (divalproex sodium [Depakote ER]) tablets for once-daily dosing vi. Nonepileptic indications: Manic episodes associated with bipolar disorder, prophylaxis of migraine headaches

Vigabatrin

Vigabatrin (Sabril) i. Mechanism of action: Irreversible inhibition of GABA transaminase ii. Pharmacokinetics: Induces CYP2C9; renal elimination; dose adjustment required for CrCl less than 60 mL/minute/1.73 m2 iii. Adverse effects: Fatigue, somnolence, nystagmus, tremor, blurred vision, vision impairment, weight gain, arthralgia, abnormal coordination, and confusional state iv. Serious adverse effect: Vision loss; increased risk with higher total dose and duration; periodic vision testing necessary; restricted distribution program; only used for refractory complex partial seizures and infantile spasms v. Only available through a REMS program vi. Available as oral powder for solution

Zonisamide (Zonegran)

i. Mechanism of action: Fast sodium channel blocker, blocks T-type calcium currents, weak carbonic anhydrase inhibitor ii. Non-arylamine sulfonamide: Avoid in patients with sulfa sensitivity; sometimes used in patients with nonserious sulfa allergies, particularly when non-acrylamides (i.e., sulfonylureas) have been used successfully iii. Pharmacokinetics: Long half-life, renal elimination iv. Adverse effects: Depression, rash, psychomotor slowing, paresthesias, kidney stones, blood dyscrasias, hyperthermia (associated with decreased perspiration, or oligohidrosis), metabolic acidosis

ASM which decreases OC, vaginal ring, progestogen implant

Brivaracetam Carbamazepine Cenobamate Clobazam Eslicarbazepine Felbamate Lamotrigine Oxcarbazepine Perampanel Phenobarbital Phenytoin Primidone Rufinamide Topiramate more than 200mg/day

The following criteria can be used to determine the possibility of withdrawal from ASM therapy

i. Patient should be seizure free for 2–5 years on seizure medication. ii. Patient should have a single type of focal or generalized seizures. iii. Patient should have a normal neurologic examination and normal IQ. iv. Patient’s EEG should have normalized with seizure medication treatment. b. If a medication is discontinued, it is usually tapered for several months; a typical regimen would reduce the dose by one-third for 1 month, reduce it by another one-third for 1 month, and then discontinue it.