Pharm Antiseizure Drugs

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1. A 12-year-old boy recently diagnosed with absence seizures started a therapy with ethosuximide, two tablets daily. Which of the following molecular actions most likely mediated the efficacy of the drug in the patient's disorder?

Explanation

Answer: B
Ethosuximide is a first line agent for absence seizures. It acts by blocking voltage-gated T type
Ca++ channels in thalamic neurons. These channels are located on the dendrites of relay
thalamic neurons which connect the thalamus to the cortex. When these channel are activated
(during sleep or, for unknown reasons, during an absence attack) the neurons provide an
oscillatory firing rate to the cortex which, on the EEG, has the characteristic 3 Hz spike and
wave readout. Excitatory input from the cortex in turn activates the thalamic neurons so
reinitiating the cycle. Therefore the absence seizure is generated by a self sustained cycle of
activity between the thalamus and the cortex. Drugs like ethosuximide and valproic acid, which
are able to block voltage-sensitive T type Ca++ channels in the thalamus, are effective in
absence seizures.
A, C, D, E, F) Therapeutic doses of ethosuximide do not have these actions.

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About This Quiz
Pharm Antiseizure Drugs - Quiz

Seizures happen because of sudden or abnormal electrical activity in the brain. When people think of seizures, they often think of convulsions in which a person's body shakes... see morerapidly and uncontrollably but not all seizures cause convulsions. See how well you understand pharm anti-seizure drugs by taking the test below. see less

2. A 35-year-old woman, who had a brain trauma 5 months ago, experienced an abrupt onset of unilateral clonic contractions of her finger that progressively involve her hand, then lower and upper arm. She was diagnosed with simple partial seizure and an appropriate drug was prescribed. Which of the following was most likely the mechanism of action of the prescribed drug?

Explanation

Answer: E
A partial seizure results from synchronous, rapid, uncontrolled firing from a group of neurons and
a loss of surrounding cell inhibition. Antiseizure drugs act to
a) enhance inhibition (i.e. by increasing CNS GABAergic activity)
b) prevent spread of synchronous activity (i.e by blocking inactivated Na+ channels, so
increasing the refractory period of nerve fibers).
Several antiseizure drugs effective against partial seizures act by blocking inactivated Na+
channels.
A) Antiseizure drugs do not affect neuromuscular transmission.
B, C, D) All these actions would decrease, not increase, the inhibitory activity of the CNS cells
surrounding the rapidly firing neurons.

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3. A 44-year-old man complained to his physician of burning and tickling in his hands and feet. The man was diagnosed with tonic-clonic seizures three years ago and has been receiving high dose of an antiseizure drug since then. Physical examination disclosed large inguinal lymph nodes and reflex testing showed lack of knee and ankle tendon reflexes. Further lab exams showed megaloblastic anemia. Which of the following drugs most likely caused the patient's symptoms and signs?

Explanation

Answer: D
The symptom and signs of the patient indicated that ha was most likely suffering from peripheral
neuropathy and lymphadenopathy which are adverse effect of long-term use of phenytoin.
Megaloblastic anemia is an adverse effect of long lasting treatment with phenytoin. The drug
inhibits the enzyme conjugase, located in the brush border of the intestinal mucosa, which
hydrolyzes the glutamate residues of ingested polyglutamates, so allowing the absorption of
monoglutamates. Patients under high doses of Phenytoin drug can show megaloblastic anemia,
lymphoid hyperplasia and paresthesias. Knee and ankle tendon reflexes are absent in about
18% of these patients.
A, B, C, E, F) All these drugs do not show the combination of the above mentioned adverse
effect.

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4. A 36-year-old woman recently diagnosed with simple partial seizures started a therapy with lamotigrine, two tablet daily. Which of the following adverse effects could most likely occur during the therapy?

Explanation

Answer: F
Lamotigrine causes a generalized erythematous skin rash in about 85 of patients taking the
drug. Several antiseizure drugs can cause skin hypersensitivity reactions but lamotigrine is by
far the drug most frequently involved. The rash is usually mild but severely affected patients may
develop Stevens-Johnson syndrome. The incidence of skin rash is higher in children and some
studies suggest that a potentially life-threatening dermatitis can develop in 1`-2 % of pediatric
patients.
A, B, C, D, E) The risk of these adverse reactions is negligible.

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5. A 41-year-old man was admitted to the hospital after he suffered a seizure with loss of consciousness at home. Two weeks ago the man was involved in a car accident and had suffered from a closed head injury. A neurological examination and EEG lead to the diagnosis of tonic-clonic seizures. The neurologist ordered an anticonvulsant drug that most likely acts with multiple mechanisms of action including blockade of NMDA receptor mediated excitation, blockade of T type Ca++ channels in thalamic neurons and increased GABA content in the brain. Which of the following drugs was most likely prescribed?

Explanation

Answer: A
The mechanisms of action of valproic acid have not been fully established but they are most
likely multiple, including:
a) State-dependent blockade of inactivated Na+ channels.
b) Blockade of NMDA receptor mediated excitation.
c) Blockade of T type Ca++ channels in thalamic neurons.
d) Increased GABA content in the brain (mechanism is uncertain)
e) Opening K+ channels (at high doses)
B, C, D, E, F) Each of these drugs does not have all the mechanisms mentioned in the question.

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6. A 52–year-old man recently diagnosed with complex partial seizures, started a therapy with carbamazepine, two tablets daily. Which of the following actions on CNS neurons most likely contributed to the therapeutic effect of the drug in the patient's disease?

Explanation

Answer: B
Carbamazepine antiseizure action most likely involves an inhibition of post tetanic potentiation of
CNS neurons surrounding the epileptic focus. Posttetanic potentiation is the production of
enhanced postsynaptic potentials that occurs after a rapid (tetanizing) train of in the presynaptic
neuron. The inhibition of posttetanic potentiation likely explains why carbamazepine (and drugs
with similar mechanism of action like phenytoin) can prevent the spread of seizure discharge
from the epileptic focus. The excessive discharge of the focus itself is not prevented and
therefore aura and EEG alterations are not eliminated by the drug.
A, E) These actions would favor, not inhibit, the spread of the discharge from the epileptic focus.
C) Long term potentiation resemble posttetanic potentiation but it is much more prolonged and
can last for days. Its enhancement would favor, not inhibit, the spread of the discharge from the
epileptic focus.
D) Long term depression is characterized by a decrease in synaptic strength. It is produced by
slower stimulation of presynaptic neurons. Its inhibition would favor, not inhibit, the spread of the
discharge from the epileptic focus

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7. A 17-year old-girl was diagnosed with epilepsy. She experienced tonic-clonic seizures that lasted about 2 minutes approximately once weekly. She was treated initially with lamotigrine, but the drug did not reduced consistently the frequency of her seizures. The neurologist decided to abandon lamotigrine and instituted a treatment with phenytoin. The blockade of which of the following type of ion channels most likely mediated the therapeutic efficacy of the drug in the patient's disease?

Explanation

Answer: B
Phenytoin blocks mainly inactivated voltage-gated Na+ channels. This blockade is frequency
dependent (also named use-dependent), that is channels that open and close at high frequency
are more susceptible to block that channels that open and close at low frequency. This can
explain why phenytoin can readily suppress the discharge from an epileptic focus (where the
neurons are discharging at high frequency) with negligible effects on normal firing neurons.
A) Na+ channels that are in a resting state are not significantly affected by antiseizure drugs
C) (see explanation above)
D, E, F) Phenytoin has negligible effects on K+ channels at therapeutic concentrations.

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8. For each numbered item select the one lettered option which is most closely associated with it (each lettered option can be selected once, more than once, or not at all). This drug is effective in all form of epilepsy in all form of epilepsy at all age groups

Explanation

Valproic acid is the correct answer because it is known to be effective in treating all forms of epilepsy in all age groups.

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9. A 2500-g girl, born at term by vaginal delivery, presented with an abnormal tuft of hair and a small dimple on the skin covering her lumbar spine. The mother, who had a long history of a bipolar disorder, was under drug treatment when the pregnancy started. She continued to take the prescribed drug for a while, in spite of the contrary advice of the gynecologist, because she was most afraid of the depressive phase of the disease. An MRI of the baby's spine disclosed that the spinal canal had remained open along several vertebrae in the lower back. A diagnosis of myelomeningocele was made. Which of the following drugs could have caused the baby's disorder?

Explanation

Answer: E
When given to the mother during pregnancy, valproic acid can increase the risk of neural tube
defect up to 20 fold. This defect can lead to a defective closure of the vertebral column, named
spina bifida. The severity of the disorder ranges from spina bifida occulta (no apparent
anomalies) to spina bifida cystica, a protruding sac that can contain meninges (meningocele)
spinal cord (myelocele) or both (myelomeningocele).
A, B, C, D, F, G) These drugs do not increase (or increase only slightly) the risk of spina bifida,
when given during pregnancy.

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10. A 26-year-old woman discovered she was unexpectedly pregnant. She had been taking regularly an oral contraceptive medication for several years. Two months ago she was diagnosed with complex partial seizures and started the prescribed therapy. Which of the following drugs was she most likely taking?

Explanation

Answer: F
There have been several reports of reduced efficacy of oral contraceptives in patients receiving
various antiseizure drugs. Carbamazepine phenytoin, phenobarbital and felbamate have been
shown to increase the metabolism of ethinylestradiol and progestins by inducing microsomal
enzymes. This effect is not associated with other anticonvulsant drugs including lamotigrine,
valproic acid ,clonazepam, gabapentin and levetiracetam.
A, B, C, D, E) (see explanation above)

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11. A 39-year-old man, diagnosed with tonic-clonic seizures two years ago, had been receiving a drug that exhibits a dose-dependent elimination kinetics. Which of the following drugs did the patient most likely take?

Explanation

Answer: C
Phenytoin is one of the very few drugs that exhibits first order elimination kinetics at low doses
but switches to a zero order elimination kinetics at higher doses, that is the elimination kinetics
of the drug is dose-dependent. Important consequence of dose-dependent kinetics are:
a) The clearance and the half life of the drug are dose-dependent.
b) The time taken to reach steady state is also dose dependent, and therefore cannot be
predicted.
c) A slight increase in dose can have a big effect on plasma levels, so leading to toxicity.
A, B, D, E, F) All these drugs follow a first order elimination kinetics.

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12. A 27-year-old woman suddenly lost consciousness in the dining room, became rigid and fell to the floor. Her respiration temporarily ceased. About one minute later jerking of all four limbs supervened for about 3 minutes, then the woman was unconscious for about 4 minutes. She was brought to the emergency room by the ambulance. Physical examination on admission showed a drowsy but alert patient who reported that a similar episode occurred about one month ago. Vital signs were normal and the neurologic examination was unremarkable. A CT scan turned out to be negative. A presumptive diagnosis was made and a therapy was ordered .Which of the following drugs was most likely prescribed for long term management of this patient?

Explanation

Answer: A
The patient most likely suffered from a tonic-clonic seizure. Since the CT scan was normal a
secondary seizure due to a brain disorder (infarct, hemorrhage, tumor, etc.) is unlikely. Moreover
the history of a previous similar episode makes the diagnosis of grand mal epilepsy most likely.
Carbamazepine, phenytoin, valproate, lamotigrine and topiramate are drugs approved by FDA
for treatment of generalized tonic-clonic seizure.
B, C) These drug are effective in absence seizures but not in tonic clonic seizures.
D, E, F) These drug are used mainly as adjunctive therapy or as second choice drugs.

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13. A 12-year-old girl was admitted to the hospital because of vomiting, drowsiness, lethargy and jaundice of six hours duration. The girl had a long history of refractory absence seizure and had been receiving several drugs during the last two years. She was presently treated with two antiseizure agents and had no absence seizures for five weeks. Physical examination showed a patient in obvious distress with extensive jaundice on the skin and sclerae. Significant lab results on admission were: alanine aminotransferase 400 U/L, total bilirubin 4 mg/L. ammonia 190 mcg/dL (normal for children 36-85). Which of the following drugs most likely caused the patients symptoms and signs?

Explanation

Answer: B
The symptoms and signs of the patient indicate that she was most likely suffering from acute
hepatitis, which is the most serious adverse effect of valproate therapy. The disease is quite rare
when valproic acid is given alone, but its occurrence is about 1/6000 when the drug is given with
other antiseizure drugs, like in the present case. Hepatitis is always serious, often lethal, and
can have a fulminant course. The pathologic lesion consists of a microvescicular steatosis
without any sign of inflammation. The cause of the disease is unknown but is most likely
idiosyncratic.
A, C, D, E, F, G) Hepatic dysfunction with all these drugs is quite unusual.

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14. A 45-year-old man with a long history of partial seizures came to his neurologist office for a control visit. The man had been receiving an antiseizure drug for the last three months. En EEG showed left temporal sharp waves and the neurologist decided to add lamotigrine to the patient's regimen. A lower dose of lamotigrine was prescribed since the drug the patient was taking can inhibit the metabolism of lamotigrine. Which of the following was most likely that drug?

Explanation

Answer: E
Valproic acid can inhibit CYP2C9 and glucuronosyltransferase so decreasing the
biotransformation of many drugs including lamotigrine, carbamazepine, phenytoin, topiramate
and felbamate.
A, B) These drug actually can induce P450 enzyme so increasing, not decreasing, the
biotransformation of many drugs.
C, D, F) These drugs do not cause relevant drugs-drugs interactions.

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15. For each numbered item select the one lettered option which is most closely associated with it (each lettered option can be selected once, more than once, or not at all). This drug binds selectively to a synaptic vescicular protein so altering the synaptic release of glutamate and GABA..

Explanation

Levetiracetam is the correct answer because it is a drug that binds selectively to a synaptic vesicular protein, thereby altering the synaptic release of glutamate and GABA.

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16. A 54-year-old woman with a previously well controlled seizure disorder was brought to the hospital because of recurrent, generalized tonic-clonic seizures. The patient was intubated and mechanically ventilated. She was treated with IV diazepam and IV fosphenytoin but the patient continued to exhibit intermittent seizures and did not regain consciousness between them. A diagnosis of refractory status epilepticus was made and an appropriate therapy was instituted. This most likely included the administration of a very large dose of which of the following drug?

Explanation

Answer: D
Provision of a patent airway and adequate oxygenation are the initial step in management of
status epilepticus. Emergency drugs include benzodiazepines for seizure control. The control
may be short-lived, however, requiring IV phenytoin infusion. If refractory status epilepticus
continues after initial treatment, additional IV phenobarbital may be given, placing the patient
in barbiturate coma.
A, B, C, E, F) All the other listed drugs are not used in case of status epilepticus.

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17. A 45-year-old man visited his physician office for consultation regarding his antimigraine medication. The man had one month history of disabling migraine headache occurring two three times weekly. About 70% of his headache attacks had been aborted with one sumatriptan tablet and rest. The patient had been suffering from idiopathic   second degree AV block diagnosed three years ago and from open angle glaucoma for four years. The physician decided to initiate a prophylactic treatment to reduce the frequency of the migraine attacks. Which of the following drugs was most likely prescribed?  

Explanation

Answer: E
Anticonvulsant medications have emerged as an important therapeutic option for the prevention
of migraine headache. Valproic acid is considered a first line agent since its efficacy has been
demonstrated in several placebo-controlled studies. Topiramate has been also recently
approved for migraine prevention.
A, B) These drugs are used for migraine prophylaxis but are contraindicated in this patient
because of AV block.
C) Amitriptyline is effective for prevention of both migraine and tension-type headache but is
contraindicated in this patient because of glaucoma.
D, F) These drugs are not effective for migraine prophylaxis.

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18. For each numbered item select the one lettered option which is most closely associated with it (each lettered option can be selected once, more than once, or not at all). This drug Inhibits GABA reuptake in both neurons and glia, so enhancing GABAergic transmission.

Explanation

Tiagabine is the correct answer because it inhibits GABA reuptake in both neurons and glia, leading to an increase in GABAergic transmission. This means that it enhances the activity of GABA, an inhibitory neurotransmitter in the brain, which can help to reduce seizures.

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19. A 6-year-old girl was diagnosed with myoclonic seizures. A brain MRI showed no overt neurologic deficit. Her past medical history was negative for epileptic seizures. Which of the following drugs would be appropriate for this patient?

Explanation

Answer: F
Myoclonic seizures consist of short episodes of bilateral jerks of a limb, several limbs or the
trunk. Consciousness is not loss (unless generalized seizure occurs). Myoclonic seizures usually
occur during childhood or adolescence (in this case they are called juvenile myoclonic epilepsy
and they are usually followed by generalized clonic-tonic seizures). Drugs for myoclonic seizures
include valproic acid, clonazepam and several second generation drugs (lamotigrine,
levetiracetam, topiramate, zonisamide).
A, B, C, D, E) These drugs are not effective (and some of them can be even dangerous) in
myoclonic seizures.

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20. A 45-year-old man was recently diagnosed with complex partial seizure and started the prescribed therapy. The patient had been suffering from AV block for one year and from nephrolithiasis for three years. Which of the following antiepileptic drugs was most likely prescribed?

Explanation

Answer: C
Carbamazepine, phenytoin and valproic acid, all are effective in complex partial seizures.
However carbamazepine and phenytoin are relatively contraindicated in case of AV block
because the drug-induced blockade of inactivated Na+ channels can slow down the heart
conduction, so exacerbating the disease. A, B ) (see explanation above)
D, E) These drugs are not effective in complex partial seizures.
F) Zonisamide is approved for adjunctive treatment of partial seizures. Moreover it can cause
nephrolithiasis in about 2.5% of patients and is therefore contraindicated in the present case.

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A 12-year-old boy recently diagnosed with absence seizures started a...
A 35-year-old woman, who had a brain trauma 5 months ago, experienced...
A 44-year-old man complained to his physician of burning and tickling...
A 36-year-old woman recently diagnosed with simple partial seizures...
A 41-year-old man was admitted to the hospital after he suffered a...
A 52–year-old man recently diagnosed with complex partial...
A 17-year old-girl was diagnosed with epilepsy. She experienced...
For each numbered item select the one lettered option which is most...
A 2500-g girl, born at term by vaginal delivery, presented with an...
A 26-year-old woman discovered she was unexpectedly pregnant. She had...
A 39-year-old man, diagnosed with tonic-clonic seizures two years ago,...
A 27-year-old woman suddenly lost consciousness in the dining room,...
A 12-year-old girl was admitted to the hospital because of vomiting,...
A 45-year-old man with a long history of partial seizures came to his...
For each numbered item select the one lettered option which is most...
A 54-year-old woman with a previously well controlled seizure disorder...
A 45-year-old man visited his physician office for consultation...
For each numbered item select the one lettered option which is most...
A 6-year-old girl was diagnosed with myoclonic seizures. A brain MRI...
A 45-year-old man was recently diagnosed with complex partial seizure...
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