58 Questions
Which of the following are possible adverse effects of antiepileptic drugs?
All of the above
What is the typical half-life of phenytoin (Dilantin)?
22 hours
Which of the following drugs can increase the effect of hydantoins?
Benzodiazepines
What is the typical onset time for carbamazepine?
4-8 hours
Which of the following antiepileptic drugs has the longest half-life?
Perampanel
What is the recommended diluent for intravenous phenytoin (Dilantin)?
Normal saline
What is the mechanism of action of hydantoins in treating seizures?
Affecting sodium channels
Which drug is considered the first-line treatment of choice for tonic-clonic and partial complex seizures?
Phenytoin
What is the role of ethosuximide in antiseizure medication?
Affects calcium channels
Which drug is commonly used in the treatment of mood disorders besides seizures?
Gabapentin
Which anticonvulsant drug is least sedating among those used to treat seizure disorders?
Phenytoin
Which class of drugs is discussed with anxiolytic drugs for its usage in treating seizures?
Benzodiazepines
What is the main mechanism of action of hydantoins?
They inhibit and stabilize electrical discharges in the motor cortex of the brain by affecting the influx of sodium ions.
What is the usual route of administration for hydantoins?
Oral
What is the therapeutic plasma level range for hydantoins?
10 to 20 mcg/mL
Which enzyme(s) are primarily responsible for the metabolism of hydantoins?
CYP2C9 and CYP2C19
What is a common hypersensitivity reaction associated with phenytoin?
Phenytoin-induced hepatitis
What is the maximum recommended rate of IV administration for phenytoin in adults?
50 mg/min
What is the overall risk of malformations in children exposed to phenytoin during pregnancy?
10%
What is a common adverse effect of hydantoins on the central nervous system?
Ataxia
What is a common adverse effect of hydantoins on the gastrointestinal system?
Gingival hyperplasia
What is a potential consequence of the abrupt discontinuation of hydantoins?
Rebound status epilepticus
Which type of seizure is phenytoin known to worsen?
Absence seizures
What is the recommended initial IV loading dose of phenytoin for status epilepticus?
12-20 mg/kg
What is the recommended maintenance dose range for ethotoin in adults?
2-3 g/day
What is the maximum recommended daily dose of rufinamide for children and adolescents with Lennox-Gastaut syndrome?
45 mg/kg/day
What is the starting dose of gabapentin for the treatment of epilepsy in adults and children over 12 years old?
300 mg tid
What is the effective dose range of gabapentin for the treatment of epilepsy in pediatric patients aged 5 years and older?
25-35 mg/kg/day
Which anticonvulsant drug is used for the short-term management of seizures when oral administration is not feasible?
Fosphenytoin
What is the maximum recommended daily dose of zonisamide for the adjunctive treatment of partial seizures in adults and adolescents?
400 mg/day
Which anticonvulsant drug is used as an adjunctive therapy for Lennox-Gastaut syndrome?
Rufinamide
What is the recommended starting dose of gabapentin for the treatment of postherpetic neuralgia in adults?
300 mg on day 1, 600 mg on day 2, 900 mg on day 3
What is the maximum daily dose of perampanel for children 12 years and older, adolescents, and adults not taking enzyme-inducing antiepileptic drugs?
12 mg
What is the initial dose of perampanel for children 12 years and older, adolescents, and adults taking enzyme-inducing antiepileptic drugs?
4 mg
At what time of day should perampanel be taken?
Bedtime
How often should the daily dose of perampanel be increased?
Every 1-2 weeks
What is the recommended form of perampanel?
Both oral suspension and tablet
What is a potential adverse effect of hydantoins that patients should be monitored for?
All of the above
What is the possible effect when hydantoins interact with allopurinol, cimetidine, diazepam, disulfiram, alcohol (acute intake), phenacemide, succinimides, or valproic acid?
Increased plasma level of hydantoins
What is the recommended action when hydantoins interact with barbiturates, carbamazepine, alcohol (chronic use), theophylline, antacids, or calcium?
Increase the hydantoin dose and monitor plasma levels
How can CYP3A4 inhibitors affect carbamazepine levels?
CYP3A4 inhibitors inhibit carbamazepine metabolism and can thus increase plasma carbamazepine levels
What is the recommended action when eslicarbazepine interacts with drugs metabolized by CYP2C19, such as phenytoin, clobazam, and omeprazole?
Dose adjustment may be needed
How can CYP3A4 inducers affect carbamazepine levels?
CYP3A4 inducers can increase the rate of carbamazepine metabolism, leading to decreased plasma levels
What is the recommended action when rufinamide interacts with CYP450 inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital?
Monitor the effectiveness of rufinamide
What is the recommended action when topiramate interacts with carbamazepine?
Monitor topiramate levels
What is the recommended action when lamotrigine interacts with estrogen-containing oral contraceptive preparations containing 30 mcg ethinylestradiol and 120 mcg levonorgestrel?
Decrease the levonorgestrel dose
How can perampanel interact with alcohol and other CNS depressants?
Increased CNS sedation, anger, confusion, depression
What is the recommended action when perampanel interacts with CYP450 inducers, such as carbamazepine, phenytoin, and oxcarbazepine?
Increased starting doses of perampanel
What is the recommended starting dose of topiramate for adults and children aged 10 years or older for monotherapy treatment of epilepsy?
25 mg twice daily
What is the usual maintenance dose range for tiagabine in enzyme-induced adult and adolescent patients over 12 years of age?
32-56 mg/day divided into two or four doses
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?
3,000 mg/day divided into two doses
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?
400 mg/day divided into two doses
If a patient is already taking lamotrigine and starts taking an oral estrogen-containing contraceptive, how should the lamotrigine dose be adjusted?
Increased by 50 mg/day weekly
What is the recommended initial dose of topiramate for the prophylaxis of migraine headaches?
25 mg once daily
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?
5-9 mg/kg/day
What is the recommended initial dose of levetiracetam for the treatment of partial-onset seizures in children aged 4-16 years?
500 mg twice daily
For the treatment of bipolar disorder in adult patients taking valproate, what is the recommended maintenance dose of lamotrigine?
100 mg/day
What is the recommended initial dose of tiagabine for adjunctive therapy in adults and children aged 12 years or older?
4 mg once daily
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
Test your knowledge on anticonvulsants and seizures mechanisms. Learn about factors that can precipitate seizures and understand how antiseizure drugs work. Explore drugs that affect sodium channels and their classification based on mechanism of action.
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