Seizures

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ANVigil
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273017
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Seizures
Updated:
2014-05-03 17:32:18
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Therapeutics
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  1. A patient with epilepsy develops chronic kidney disease (SCr
    = 6.1). Which of the following anticonvulsants would require dose adjustments
    in this patient?

    I. Gabapentin
    II. Topiramate
    III. Lamotrigine
    IV. Phenytoin
    • I, II, IV
    • Gabapentin, Topiramate, Lamotrigine, Phenytoin








    • •Gabapentin and topiramate
    • would require dose adjustments because they are renally eliminated.

    • •Protein
    • binding
    • is significantly altered in patients with renal failure; therefore, patients
    • receiving phenytoin may
    • have a significant increase in their free concentration, which results in signs
    • and symptoms of toxicity. Thus, a dose adjustment would be required.
  2. An infant who is born to a mother chronically on phenobarbital
    should receive which of the following after delivery?

    A. Folic acid

    B. Vitamin K

    C. Pyroxidine

    D. Estrogen

    E. MHD
    Vitamin K









    • •Vitamin
    • K should be given to the mother
    • before delivery and to the newborn.

    • •Vitamin
    • K–deficient
    • hemorrhagic disease can occur in the newborn of a mother who received phenobarbital
    • or phenytoin chronically.


    • •Hemorrhage
    • generally
    • occurs during the first 24 hours after birth and may be severe or even fatal.

    • •The exact
    • mechanism is unknown but may involve anticonvulsant induction of fetal liver
    • microsomal enzymes that deplete fetal reserves of vitamin K to cause
    • suppression of the vitamin K–dependent coagulation factors II, VII, IX, and X.
  3. Taking gabapentin with antacids may have what effect on its pharmacokinetic
    properties?

    A. Increased
    absorption

    B. Decreased
    absorption

    C. Decreased
    T-max
    D. Increased C-max

    E. No effect
    B. Decreased Absorption









    • •Antacids
    • may decrease the extent of absorption of gabapentin by approximately 20%. For
    • this reason, antacids should be given used at least 2 hours before or after
    • gabapentin is administered.
  4. The therapeutic range for carbamazepine is:

    A. 1-2 mg/L

    B. 4-12 mg/L

    C. 10-20
    mg/L

    D. 50-100
    mg/L

    E. 15-45
    mg/L
    B. 4-12 mg/L 








    • •In
    • general the reference range for carbamazepine is 4–12 mg/L. If a patient is
    • receiving monotherapy the range is generally considered to be 8–12 mg/L. If a
    • patient is receiving numerous anticonvulsants (i.e., polytherapy) the
    • reference range is 4–8 mg/L.
  5. Which of the following is associated with topiramate
    therapy?

    A. Weight
    gain

    B. Thrombocytopenia

    C. Insomnia

    D. Kidney
    stones
    E. Alopecia
    D Kidney stones








    • •Kidney
    • stones have been associated with chronic topiramate therapy.

    • •Topiramate causes
    • weight loss, not weight gain.

    • •Valproic acid
    • is associated with thrombocytopenia and alopecia.
    • Although insomnia is associated with felbamate,
    • most anticonvulsants cause drowsiness on initiation.
  6. Which of the following are not associated with any drug-drug interactions?

    •I.
    Gabapentin

    •II.
    Carbamazepine

    •III.
    Levetiracetam

    A.  I only

    B.  II only

    C.  I and
    III only

    D.  II and
    III only

    E.  I and
    II only

    F.  III
    only
    C I and III








    • •At
    • this time, neither gabapentin nor levetiracetam are
    • associated with significant drug-drug interactions.

    • •The absorption
    • of gabapentin may be reduced by concurrent administration of aluminum- and/or
    • magnesium-containing antacids; hence antacids should be given 2 hours before or
    • after a dose of gabapentin.

    • •Carbamazepine is an
    • inducer that is associated with numerous drug-drug interactions.
  7. Which of the following medications may cause seizures in an adult patient with renal
    failure?


    •A. Meperidine

    •B. Phenobarbital

    •C. Carbamazepine

    •D. Lamotrigine

    •E. Theophylline
    A. Meperidine








    • •Normeperidine, a
    • metabolite of meperidine, can
    • accumulate in patients with renal failure who receive normal doses and cause
    • seizures. The other agents listed are not eliminated renally in
    • adults.
  8. Which of the following anticonvulsants causes tremor?

    •A. Carbamazepine

    •B. Phenobarbital

    •C. Lamotrigine

    •D. Zonisamide

    •E. Valproic acid
    E. Valproic Acid








    • •Valproic acid
    • is associated with a dose-dependent tremor (shaking of the hands or other body
    • parts). Tremor tends to be worse when the serum concentration is elevated above
    • 70 mg/L.
  9. Which of the following is true regarding phenytoin?

    •A.  The maximum
    rate of intravenous administration is 50 mg/min.

    •B.  If intravenous
    access can't be established, phenytoin can be given IM.

    •C. 
    Because phenytoin
    contains propylene glycol it is soluble as any IV fluid.

    •D. It is an
    inhibitor of the cytochrome P450 system.

    •E. A major
    limitation to the use of the product in pediatric patients is the lack of a
    commercially available liquid formulation.
    • A. Max rate 50 mg/min.
    • Because phenytoin contains propylene glycol and is itself cardiotoxic, the
    • IV formulation should not be infused faster than 50 mg/min. Phenytoin is
    • extremely alkaline (pH ~13). Not only is IM administration associated with
    • tissue damage, it is erratically absorbed. Phenytoin can only be admixed with
    • normal saline, is an inducer, and is also available as a suspension and a
    • chewable tablet.
  10. Patients should be instructed to drink plenty of fluids while taking which of the
    following anticonvulsants?

    •A. Gabapentin


    •B. Carbamazepine


    •C. Phenobarbital


    •D. Topiramate

    •E. Levetiracetam
    • D. Topiramate
    • Topiramate and zonisamide use have been associated with an increased risk for calcium phosphate kidney
    • stones.

    • The risk of kidney stones may be increased in those who have a personal or family
    • history of kidney stones.

    • Patients should be instructed to drink plenty of fluids (6–8 ounces of water per day) to
    • decrease the likelihood of stone formation.
  11. The therapeutic range for phenobarbital is:

    •A. 1-2 mg/L

    •B. 4-12 mg/L

    •C. 10-20
    mg/L

    •D. 50-100
    mg/L

    •E. 15-45
    mg/L
    • E. 15-45
    • •In
    • assessment of chronic therapy the reference range is considered to be 15-45
    • mg/L.

    • •Because
    • the
    • anticonvulsant effect is concentration related and is linear, many
    • practitioners will target higher concentrations in patients who are acutely
    • seizing.

    • •Some studies
    • report concentrations as high as 300
    • mg/L.
  12. Which of the following has decreasing bioavailability with decreasing age?

    •A. Fosphenytoin

    •B. Gabapentin

    •C. Lamotrigine

    •D. Oxcarbazepine

    •E. Topiramate
    • B. Gabapentin
    • •The bioavailability of gabapentin is poor (60%) in adults and decreases further
    • with decreasing age.
    • •(Decreasing
    • age - ??? younger???)
  13. Which of the following medications is available only through specialty pharmacies?

    •A. Vigabatrin

    •B. Gabapentin

    •C. Fosphenytoin

    •D. Levetiracetam

    •E. Lamotrigine
    • A. Vigabatrin
    • Because of concerns related to an adverse effect (i.e., loss of peripheral vision),
    • both the ability to prescribe and the availability of this this product are
    • restricted. The product must be acquired from a specialty pharmacy.
  14. Which of the following anticonvulsants are available in a liquid, chewable tablet,
    and intravenous formulation?

    •I.
    Carbamazepine

    •II.
    Phenytoin

    •III.
    Valproic
    acid


    •A. II only

    •B. III only

    •C. I only

    •D. I and
    II only

    •E. I, II,
    and III
    • II. Only
    • Only phenytoin is available as a liquid (125 mg/5 mL), chewable tablet (50 mg), and
    • in an intravenous dosage form. Carbamazepine is not available in an IV dosage
    • form and valproic acid
    • is not available as a chewable tablet.
  15. A new anticonvulsant has just been approved by the FDA. Its bioavailability is
    > 95%, and it is highly protein bound to alpha 1-acid glycoprotein. It undergoes
    extensive hepatic metabolism by CYP2C9. Less than 5% is excreted unchanged in
    the urine. It is known to inhibit CYP3A4. A patient on this anticonvulsant has
    developed significant depression and is being started on an antidepressant that
    is 93% bound to albumin and is a potent inhibitor of CYP2C19. The
    antidepressant is a pro-drug that is metabolized by CYP3A4 to an active
    metabolite that is hepatically
    cleared by CYP2C9. The neurologist wants to know if any drug interactions may
    occur that would necessitate a change in drug dosage. Which of the following is
    the appropriate response?

    •A. No drug interactions should occur in this patient.

    •B. The dose of the anticonvulsant should be reduced because of a potential protein-binding interaction that would increase the serum concentration of the anticonvulsant.

    •C. The dose of the anticonvulsant should be increased.

    •D. The patient may not benefit from the antidepressant, and another antidepressant that is not metabolized by CYP3A4 should be used.

    •E. Because of an interaction in the gut that decreases bioavailability, the dose should be
    increased.
    D. Patient may not benefit and another antidepressant that is not metabolized by CYP3A4 should be used

    • Because the new anticonvulsant inhibits CYP3A4, D is the correct answer. Because the
    • antidepressant is a pro-drug, which must be metabolized by CYP3A4 to become
    • active, it may not be effective. An alternative antidepressant should be
    • considered.
  16. Which of the following statements would be true
    for a patient receiving phenytoin who has a known polymorphism for CYP2C19?

    •A. The patient
    would require a larger maintenance dose of phenytoin.

    •B. The patient
    would require the same dose of phenytoin regardless of CYP2C19 status.

    •C. The maintenance
    dose of phenytoin would need to be reduced.

    •D. If the
    patient is receiving fosphenytoin, the
    loading dose should be reduced, but the patient would require a larger
    maintenance dose.
    • C. Would need to reduce maintenance dose of phenytoin.
    • Individuals who did not receive the gene associated with CYP2C19 from one or both parents
    • will not have a decreased ability to metabolize phenytoin and will require a
    • smaller dose of the medication to produce the same effect.
  17. A patient on which of the following medications should be made aware of the
    importance of good oral hygiene?

    •A. Felbamate

    •B. Phenytoin

    •C. Zonisamide

    •D. Phenobarbital

    •E. Levetiracetam
    • B. Phenytoin 
    • •Phenytoin
    • may cause gingival hyperplasia
    • (i.e., overgrowth of the gums).

    • •Hence,
    • patients should be instructed to brush and floss daily and to have regular
    • visits with the dentist.
  18. Which of the following formulations are available in an extended-release formulation?


    •I.
    Pregabalin

    •II.
    Zonisamide

    •III.
    Divalproex
    sodium

    •IV.
    Levetiracetam


    •A.  I and
    II

    •B.  II and
    III

    •C.  III and
    IV

    •D.  I, II,
    and IV

    •E.  I,
    III, and IV
    III and IV


    • Please
    • refer to Table 27-2 and Table 27-3
  19. Which of the following is true of the pharmacokinetics of gabapentin?


    •A. It is
    highly protein bound.

    •B. It undergoes
    significant hepatic metabolism.

    •C. It is
    100% renally
    eliminated.

    •D. Its bioavailability
    is reasonably good at 80%.

    •E. Its half-life
    exceeds 24 hours in normally healthy individuals.
    • C. Gabapentin is 100% renally
    • eliminated and requires dosage adjustment in patients with renal failure.

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