Antiseizure Drugs Flashcards
Goals of therapy
Eliminate seizures
Avoid side effects
Achieve best possible psychosocial function
Principles of AED therapy
Verify a diagnosis of epilepsy
Acute symptomatic seizures (e.g. hyponatremic seizure or seizure related to drug intoxication) is not epilepsy and does not require initiation of an AED.
Many other things can mimic an epileptic seizure, such as psychogenic non-epileptic seizures and syncope.
Select an AED based on seizure-type, other medications and co-morbidities, and potential adverse effects.
Manage adverse effects
Attempt to get seizure-freedom with monotherapy.
Monitory therapy with serum drug levels, if available.
Drugs for Focal-onset seizures:
ALL AEDs except ethosuxamide (based on FDA approval)
There is no clear front-runner to choose from based on efficacy alone. You must make a selection based on other things, like drug interractions and side effects.
Drugs for absence seizures
Ethosuxamide (works for nothing else)
Valproic acid
Zonisamide
Drugs for Primary generalized seizures
Valproic acid
Lamotrigine
Topiramate
Zonisamide
Levetiracetam
Perampanel
Drugs for myoclonus
Valproic acid
Levetiracetame
Zonisamide
Criteria for surgery
Some patients with epilepsy need to have surgery to reduce seizure frequency. One criteria commonly used to recommend epilepsy surgery is the use of at least two AEDs over at least two years, which fail to achieve seizure freedom.
Efficacy of first AED
The first drug you choose has about a 60% chance of seizure freedom. Each drug you choose after that has diminishing returns unless use is limited by side effects (in which case you get a do-over).
What are complex partial seizures and drugs of choice
Complex Partial Seizures
Focal onset seizures with altered awareness
ALL AEDs are useful except for ethosuxamide
“classic” drugs of choice:
carbamazepine
phenytoin
valproic acid
oxcarbazepine
lamotrigine
lacosamide
Side effects of Pheytoin
Gum hypertrophy
Facial coarsening and hirsutism
Osteopenia
Teratogenesis
Ataxia with cerebellar atrophy
Side effects of Valproic acid
Weight gain
Tremor
Alopecia
Side effects of topiramate
Nausea and weight loss
Nephrolithiasis
Glaucoma exacerbation
Side effects of Levetiracetam
Irritability and mood disorder exacerbation
Drugs that interact with Broad spectrum CYP inducers
Carbamazepine
Phenytoin
Phenobarbital
Primidone
Drugs that interact with CYP3A inducers
Oxcarbazepine
Topiramate
Felbamate
Drugs that interact with CYP450 inhibitors
Valproic acid
Drugs that have NO effects on the CYP system
Levetirecetam
Gabapentin
Lamotrigine
Tiagabine
Zonisamide
Drugs that carry a risk of stevens johnson syndrome
Carbamazepine
Oxcarbazepine
Valproic acid
Phenytoin
Phenobarbital
Ethosuxamide
Lamotrigine
Zonisamide
Drugs with hepatotoxicity
Carbamazepine
Oxcarbazepine
Valproic acid
Phenytoin
Phenobarbital
Felbamate
Drugs that cause Leukopenia/aplastic anemia
Carbamazepine
Oxcarbazepine
Valproic acid
Phenobarbital
Ethosuxamide
Zonisamide
Felbamate
How does Voltage-gated sodium channel modulation work
The most important known AED mechanism of action is modulation of sustained repetitive firing, usually through modulation of voltage-gated sodium channel function.
Benzodiazapenes MOA
GABA receptor modulation
The second most important AED mechanism of action is enhancement of GABAA receptor function and therefore, enhancement of synaptic inhibition.
AED used for tremor
Primidone
AED used for pain
gabapentin, pregabalin
AED used for migraine
topiramate, valproic acid
AED used for mood disorder
lamotirigine, valproic acid, topiramate
Phenytoin MOA and indication
Mechanism of action: Sodium channel modulator
Indication: FDA approved for focal onset seizures
Phenytoin pharmokinetics
Liver metabolism, which is nonlinear
Phenytoin switches from first-order to zero-order kinetics in the middle of its therapeutic dose range.
Interracts with mutliple drugs (broad spectrum CYP inducer)
Twice daily dosing, half-life of ~22 hours (good if you miss a dose)
Carbamazepine MOA, indications, pharmacokinetics, adverse effects
Mechanism of action: Sodium channel modulator
Indication: FDA approved for patrial onset seizures
Phamacokinetics:
Liver metabolism
Broad spectrum CYP inducer
TID dosing, half life 8-22 hours
Adverse effects:
Hyponatremia
Hepatitis
Aplastic anemia
Ataxia
Gabapentin indication and pharmacokinetics
Indication: FDA approved for focal onset seizures
Pharmacokinetics: very favorable
No active metabolites or protein binding
93% excreted unchanged in urine
Does not induce hepatic enzymes
Low interraction with other AEDs
TID or QID dosing, half life 5-7 hours
Lamotrigine indication, pharmacokinetics, side effects
Indication: FDA approved for focal onset seizures but commonly used also in generalized seizures
Pharmacokinetics:
Metabolized in the liver but not CYP450
daily or BID dosing, half life 12-60 hours
High rate of rash, including Stevens Johnson syndrome
Levetiracetam MOA, indication, pharmacokinetics, side effects
Mechanism of action: not entirely clear
Indication: FDA approved for focal onset seizures but also frequently used in generalized seizures
Pharmacokinetics:
2/3 excreted unchanged and 1/3 metabolized in the liver
BID dosing, half-life 6-8 hours
Adverse effects: irritability and aggressiveness
Fetal malformations associated with each drug
Structural teratogenesis with 1st trimester exposure and cognitive teratogenesis is with exposure throughout pregnancy
Valproate- Associated with spina bifida, hypospadias, lower verbal IQ and autism, may be dose dependent
Phenobarbital is associated with cardiac malformations
Topiramate- Associated with facial clefts
Carbamazepine- Spina bifida
Phenytoin- hypospadias and cardiac defects
Levetiracetam- Only 2 major malformations occurred (inguinal hernia and reflux requiring surgery)
Folic acid decreases the risk of neural tube defects, lower verbal IQ and the risk of spontaneous miscarriage (1-4 mg)
