Anticonvulsants and Seizures Mechanisms Quiz

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Questions and Answers

Which of the following are possible adverse effects of antiepileptic drugs?

  • Hyperglycemia and tinnitus
  • Skin rashes and photophobia
  • Gynecomastia and polyarthropathy
  • All of the above (correct)

What is the typical half-life of phenytoin (Dilantin)?

  • 12-29 hours
  • 3-9 hours
  • 1.5-3 hours
  • 22 hours (correct)

Which of the following drugs can increase the effect of hydantoins?

  • Barbiturates
  • Benzodiazepines (correct)
  • Theophylline
  • Rifampin

What is the typical onset time for carbamazepine?

<p>4-8 hours (A)</p> Signup and view all the answers

Which of the following antiepileptic drugs has the longest half-life?

<p>Perampanel (C)</p> Signup and view all the answers

What is the recommended diluent for intravenous phenytoin (Dilantin)?

<p>Normal saline (B)</p> Signup and view all the answers

What is the mechanism of action of hydantoins in treating seizures?

<p>Affecting sodium channels (B)</p> Signup and view all the answers

Which drug is considered the first-line treatment of choice for tonic-clonic and partial complex seizures?

<p>Phenytoin (C)</p> Signup and view all the answers

What is the role of ethosuximide in antiseizure medication?

<p>Affects calcium channels (D)</p> Signup and view all the answers

Which drug is commonly used in the treatment of mood disorders besides seizures?

<p>Gabapentin (D)</p> Signup and view all the answers

Which anticonvulsant drug is least sedating among those used to treat seizure disorders?

<p>Phenytoin (D)</p> Signup and view all the answers

Which class of drugs is discussed with anxiolytic drugs for its usage in treating seizures?

<p>Benzodiazepines (C)</p> Signup and view all the answers

What is the main mechanism of action of hydantoins?

<p>They inhibit and stabilize electrical discharges in the motor cortex of the brain by affecting the influx of sodium ions. (A)</p> Signup and view all the answers

What is the usual route of administration for hydantoins?

<p>Oral (A)</p> Signup and view all the answers

What is the therapeutic plasma level range for hydantoins?

<p>10 to 20 mcg/mL (B)</p> Signup and view all the answers

Which enzyme(s) are primarily responsible for the metabolism of hydantoins?

<p>CYP2C9 and CYP2C19 (C)</p> Signup and view all the answers

What is a common hypersensitivity reaction associated with phenytoin?

<p>Phenytoin-induced hepatitis (C)</p> Signup and view all the answers

What is the maximum recommended rate of IV administration for phenytoin in adults?

<p>50 mg/min (A)</p> Signup and view all the answers

What is the overall risk of malformations in children exposed to phenytoin during pregnancy?

<p>10% (B)</p> Signup and view all the answers

What is a common adverse effect of hydantoins on the central nervous system?

<p>Ataxia (D)</p> Signup and view all the answers

What is a common adverse effect of hydantoins on the gastrointestinal system?

<p>Gingival hyperplasia (C)</p> Signup and view all the answers

What is a potential consequence of the abrupt discontinuation of hydantoins?

<p>Rebound status epilepticus (C)</p> Signup and view all the answers

Which type of seizure is phenytoin known to worsen?

<p>Absence seizures (A)</p> Signup and view all the answers

What is the recommended initial IV loading dose of phenytoin for status epilepticus?

<p>12-20 mg/kg (B)</p> Signup and view all the answers

What is the recommended maintenance dose range for ethotoin in adults?

<p>2-3 g/day (A)</p> Signup and view all the answers

What is the maximum recommended daily dose of rufinamide for children and adolescents with Lennox-Gastaut syndrome?

<p>45 mg/kg/day (B)</p> Signup and view all the answers

What is the starting dose of gabapentin for the treatment of epilepsy in adults and children over 12 years old?

<p>300 mg tid (D)</p> Signup and view all the answers

What is the effective dose range of gabapentin for the treatment of epilepsy in pediatric patients aged 5 years and older?

<p>25-35 mg/kg/day (A)</p> Signup and view all the answers

Which anticonvulsant drug is used for the short-term management of seizures when oral administration is not feasible?

<p>Fosphenytoin (B)</p> Signup and view all the answers

What is the maximum recommended daily dose of zonisamide for the adjunctive treatment of partial seizures in adults and adolescents?

<p>400 mg/day (B)</p> Signup and view all the answers

Which anticonvulsant drug is used as an adjunctive therapy for Lennox-Gastaut syndrome?

<p>Rufinamide (A)</p> Signup and view all the answers

What is the recommended starting dose of gabapentin for the treatment of postherpetic neuralgia in adults?

<p>300 mg on day 1, 600 mg on day 2, 900 mg on day 3 (D)</p> Signup and view all the answers

What is the maximum daily dose of perampanel for children 12 years and older, adolescents, and adults not taking enzyme-inducing antiepileptic drugs?

<p>12 mg (C)</p> Signup and view all the answers

What is the initial dose of perampanel for children 12 years and older, adolescents, and adults taking enzyme-inducing antiepileptic drugs?

<p>4 mg (D)</p> Signup and view all the answers

At what time of day should perampanel be taken?

<p>Bedtime (C)</p> Signup and view all the answers

How often should the daily dose of perampanel be increased?

<p>Every 1-2 weeks (B)</p> Signup and view all the answers

What is the recommended form of perampanel?

<p>Both oral suspension and tablet (C)</p> Signup and view all the answers

What is a potential adverse effect of hydantoins that patients should be monitored for?

<p>All of the above (D)</p> Signup and view all the answers

What is the possible effect when hydantoins interact with allopurinol, cimetidine, diazepam, disulfiram, alcohol (acute intake), phenacemide, succinimides, or valproic acid?

<p>Increased plasma level of hydantoins (B)</p> Signup and view all the answers

What is the recommended action when hydantoins interact with barbiturates, carbamazepine, alcohol (chronic use), theophylline, antacids, or calcium?

<p>Increase the hydantoin dose and monitor plasma levels (B)</p> Signup and view all the answers

How can CYP3A4 inhibitors affect carbamazepine levels?

<p>CYP3A4 inhibitors inhibit carbamazepine metabolism and can thus increase plasma carbamazepine levels (D)</p> Signup and view all the answers

What is the recommended action when eslicarbazepine interacts with drugs metabolized by CYP2C19, such as phenytoin, clobazam, and omeprazole?

<p>Dose adjustment may be needed (C)</p> Signup and view all the answers

How can CYP3A4 inducers affect carbamazepine levels?

<p>CYP3A4 inducers can increase the rate of carbamazepine metabolism, leading to decreased plasma levels (B)</p> Signup and view all the answers

What is the recommended action when rufinamide interacts with CYP450 inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital?

<p>Monitor the effectiveness of rufinamide (B)</p> Signup and view all the answers

What is the recommended action when topiramate interacts with carbamazepine?

<p>Monitor topiramate levels (A)</p> Signup and view all the answers

What is the recommended action when lamotrigine interacts with estrogen-containing oral contraceptive preparations containing 30 mcg ethinylestradiol and 120 mcg levonorgestrel?

<p>Decrease the levonorgestrel dose (C)</p> Signup and view all the answers

How can perampanel interact with alcohol and other CNS depressants?

<p>Increased CNS sedation, anger, confusion, depression (D)</p> Signup and view all the answers

What is the recommended action when perampanel interacts with CYP450 inducers, such as carbamazepine, phenytoin, and oxcarbazepine?

<p>Increased starting doses of perampanel (A)</p> Signup and view all the answers

What is the recommended starting dose of topiramate for adults and children aged 10 years or older for monotherapy treatment of epilepsy?

<p>25 mg twice daily (C)</p> Signup and view all the answers

What is the usual maintenance dose range for tiagabine in enzyme-induced adult and adolescent patients over 12 years of age?

<p>32-56 mg/day divided into two or four doses (C)</p> Signup and view all the answers

For the treatment of partial-onset seizures in adults and adolescents aged 16 years or older, what is the maximum recommended daily dose of levetiracetam?

<p>3,000 mg/day divided into two doses (C)</p> Signup and view all the answers

For the treatment of bipolar disorder in adult patients taking enzyme-inducing antiepileptic drugs (AEDs) but not valproate, what is the recommended maintenance dose of lamotrigine?

<p>400 mg/day divided into two doses (C)</p> Signup and view all the answers

If a patient is already taking lamotrigine and starts taking an oral estrogen-containing contraceptive, how should the lamotrigine dose be adjusted?

<p>Increased by 50 mg/day weekly (B)</p> Signup and view all the answers

What is the recommended initial dose of topiramate for the prophylaxis of migraine headaches?

<p>25 mg once daily (C)</p> Signup and view all the answers

For the adjunctive treatment of partial seizures, Lennox-Gastaut syndrome, and epilepsy in pediatric patients aged 1-16 years, what is the total recommended daily dose range for topiramate?

<p>5-9 mg/kg/day (C)</p> Signup and view all the answers

What is the recommended initial dose of levetiracetam for the treatment of partial-onset seizures in children aged 4-16 years?

<p>500 mg twice daily (C)</p> Signup and view all the answers

For the treatment of bipolar disorder in adult patients taking valproate, what is the recommended maintenance dose of lamotrigine?

<p>100 mg/day (C)</p> Signup and view all the answers

What is the recommended initial dose of tiagabine for adjunctive therapy in adults and children aged 12 years or older?

<p>4 mg once daily (C)</p> Signup and view all the answers

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Study Notes

Pharmacodynamics of Hydantoins

  • Hydantoins inhibit and stabilize electrical discharges in the motor cortex of the brain
  • They affect the influx of sodium ions into the neuron during depolarization and repolarization
  • They slow the propagation and spread of abnormal discharges
  • They also affect the brainstem's contribution to grand mal seizures and have antiarrhythmic properties

Pharmacokinetics of Hydantoins

  • The usual route of administration is oral
  • Absorption occurs in the small intestine and is slow, although the rate varies with the form of the drug
  • Hydantoins enter the brain quickly and are then redistributed to other body tissues, saliva, and breast milk
  • The rate and degree of absorption from intramuscular (IM) administration is erratic, generally resulting in lower plasma levels than the oral route
  • Hydantoins are 87% to 93% protein bound and may be competitively displaced
  • The therapeutic plasma level range is 10 to 20 mcg/mL and correlates well with treatment effect

Metabolism and Excretion of Hydantoins

  • Metabolism of hydantoins takes place in the liver by CYP2C9 and CYP2C19
  • Excretion is via the kidneys
  • Plasma half-lives range from 6 to 24 hours

Precautions and Contraindications of Hydantoins

  • Hydantoins are contraindicated if the patient has documented hypersensitivity
  • Phenytoin-induced hepatitis is a common hypersensitivity reaction
  • Other hypersensitivity reactions include fever, rash, arthralgias, and lymphadenopathy
  • Rapid IV administration of phenytoin may cause severe cardiovascular events, and death has resulted
  • Phenyltoin is contraindicated in sinus bradycardia, sinoatrial block, second- and third-degree atrioventricular block, and Stokes-Adams syndrome
  • It should be used cautiously in patients with hepatic or renal disease

Adverse Drug Reactions of Hydantoins

  • Possible adverse effects include:
    • CNS effects: agitation, ataxia, confusion, dizziness, drowsiness, headache, and nystagmus
    • Cardiovascular effects: hypotension, tachycardia, atrial and ventricular conduction depression, and ventricular fibrillation
    • Gastrointestinal effects: nausea, vomiting, anorexia, altered taste, constipation, dry mouth, and gingival hyperplasia
    • Genitourinary effects: urinary retention and reddish-brown discoloration of the urine
    • Other effects: skin rashes, hyperglycemia, tinnitus, gynecomastia, coarsening of facial features, and polyarthropathy

Drug Interactions of Hydantoins

  • Interactions that increase the hydantoin's effect:
    • Benzodiazepines, cimetidine, disulfiram, TCAs, salicylates, and valproic acid
  • Interactions that decrease the hydantoin's effect:
    • Barbiturates, rifampin, theophylline, influenza vaccine, pyridoxine, and antacids
  • Acute alcohol intake may increase phenytoin serum levels, whereas chronic alcohol use may decrease levels
  • IV phenytoin should only be mixed with normal saline and should not be mixed with dextrose-containing IV solutions because a precipitate may form

Anticonvulsants

  • Antiseizure drugs are often classified by their mechanism of action:

    • Sodium channel blockers: hydantoins, carbamazepines, lacosamide, lamotrigine, rufinamide, and zonisamide
    • Calcium channel blockers: ethosuximide
    • GABA receptors: benzodiazepines, phenobarbital, tiagabine, vigabatrin
    • Glutamate receptors: perampanel
    • Other mechanisms of action: felbamate, topiramate, valproate, brivaracetam, gabapentin, levetiracetam, pregabalin### Tiagabine (Gabitril)

  • Adjunctive therapy in adults and children ≥12 yr for partial seizures

  • Initial dose: 4 mg/d for 1 week, increased by 4 mg/d every week up to 32-56 mg/d divided bid or qid

  • Tablets: 2 mg, 4 mg, 12 mg, and 16 mg

Topiramate (Topamax)

  • Monotherapy for epilepsy in adults and children ≥10 yr
  • Initial dose: 25 mg bid, increased by 25-50 mg/d every week up to 200 mg bid
  • Tablets: 25 mg, 50 mg, 100 mg, and 200 mg; sprinkle capsules: 12 mg and 25 mg
  • Adjunctive therapy in adults ≥17 yr for partial seizures and Lennox-Gastaut syndrome
  • Initial dose: 25-50 mg/d, increased by 25-50 mg/d every week up to 200-400 mg/d
  • Pediatric patients (age 1-16 yr): initial dose 1-3 mg/kg/d, increased by 1-3 mg/kg/d every 1-2 weeks up to 5-9 mg/kg/d

Migraine Prophylaxis

  • Initial dose: 25 mg qd, increased by 25 mg/d every week up to 100 mg/d

Levetiracetam (Keppra)

  • Partial-onset seizures in adults and adolescents ≥16 yr
  • Initial dose: 500 mg bid, increased by 1,000 mg/d every 2 weeks up to 3,000 mg/d
  • Children 4-16 yr: initial dose 1,000 mg/d divided bid, increased by 1,000 mg/d every 2 weeks up to 3,000 mg/d

Lamotrigine

  • Bipolar disorder
    • Adults not taking enzyme-inducing AEDs or valproate: initial dose 25 mg/d, increased by 25-50 mg/d every week up to 200 mg/d
    • Adults taking enzyme-inducing AEDs and not taking valproate: initial dose 50 mg/d, increased by 50-100 mg/d every week up to 400 mg/d
    • Adults taking valproate: initial dose 25 mg every other day, increased by 25-50 mg/d every week up to 100 mg/d
  • Seizures in children 2-12 yr: initial dose 0.12 mg/kg/d, increased by 0.3 mg/kg/d every week up to 1-5 mg/d with a maximum of 200 mg/d
  • Women taking oral contraceptives: lamotrigine dose increased by 50 mg/d weekly

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