Anti-Epileptics Flashcards
First line treatment to stop status epilepticus
Other options
Benzodiazepines- lorazepam. Stop the seizure to avoid duration of activity causing permanent neurological damage
Fosphenytoin, phenobarbital (kids), valproate, midazolam drip, pentobarbital drip, isoflurane.
Carbamazepine (tegretol)
Indication- partial onset seizure only. Also useful for pain (trigeminal neuralgia) or mood stabilizer. May worsen absence or myoclonic seizures.
Pharmacokinetics- liver metabolized, moderate protein binding, many interactions (hepatic inducer)
Adverse effects- drowsiness, nausea, dizziness, visual disturbances,rash. Rare: aplastic anemia, sever rash, liver failure, ostereoporosis or atherosclerosis in long term usage.
MOA- blocks voltage gated sodium channels
Carbamazepine metabolism side effect
Can experience auto-induction: induces its own metabolism. Serum half life may fall by 50% during first two weeks of therapy.
Will need to increase the dose after obtaining serum level and confirming compliance
Carbamazepine interactions
Phenobarbital, phenytoin, felbamate, primidone induce P-450 3A4, lowering CBZ levels
Depakote inhibits metabolism of CBZ and its epoxide- may result in toxicity/SEs
Macrolides, isoniazid, fluoxetine, calcium channel blockers, cimetidine, propoxyphene inhibit P-450 3A4, increasing CBZ levels
Grapefruit juice and St. John’s Wort are also inducers
Phenytoin (Dilantin)
Indications- partial onset seizures. Many worsen absence and myoclonic seizures. Can put them into status if misdiagnosed.
Second line, difficulty dosing
Pharmacokinetics- non-linear with clinically important saturation, highly protein bound, many interactions
MOA- sodium channel inactivation
Adverse effects- drowsiness, dizziness, unsteady gait, hum hypertrophy, hirsutism, rash, rare: liver failure, aplastic anemia, sever rash, SLE-like syndrome
Phenytoin kinetics
Zero order.
Metabolized by P450 oxidase system
First step is rate limited, so he serum relationship is non-linear
As dose is increased, plasma concentrations rise linearly initially until the point of enzyme saturation (which is different for every patient)
At this point, the serum concentration will rise in a much steeper fashion and the half life will become longer- increased toxicity (imbalance, falls, ataxia, sedation, nystagmus, etc.)
Liver metabolism saturable at therapeutic doses
Wait 2-3 weeks for steady-state
Lamotrigine (lamictal)
Indications- partial or generalized onset seizures
First line- newer but a generic exists, well tolerated, broad spectrum
Pharmacokinetics- liver metabolized, low protein binding, few interactions, oral contraceptives lower amount of lamictal
MOA- blockage of voltage gated sodium channels
Adverse effects- sedation, dizziness. Rare severe rash (Stevens Johnson syndrome- fatal). Slow titration recommended
Levetiracetam (keppra)
Indicated- partial or generalized onset seizure. First line: newer but generic exists, well tolerated, broad spectrum
Pharmacokinetics- not liver metabolized*, no protein binding, no important interactions. Excreted in urine, so watch for renal impairment
MOA- binds to a presynaptic vesicle glycoprotein 2A reducing NT release. Also acts on HVA calcium channels, AMPA receptors
Adverse effects- drowsiness, Keppra rage, rash, liver failure, aplastic anemia not seen
Valproate (Depakote)
Indications- partial or generalized. ‘Drug of choice’ for most generalized onset seizures, but large side effect profile and higher risk of teratogensis. Also approved for bipolar disorder
Pharmacokinetics- liver metabolized, highly protein bound, many interactions
MOA- sodium channel inactivation, increases GABA via inhibition of GABA transaminase
Adverse effects- drowsiness, weight gain, tremor, hair loss, rash is rare. Liver failure rare but more common in children. Osteoporosis. polycystic ovarian syndrome.
Gabapentin (Neurontin)
Indications- FDA approved for partial onset only (2nd line). Also helpful for neuropathic pain, migraine
Pharmacokinetics- eliminated by renal excretion as unchanged drug, low protein binding
MOA- designed as GABA analog, but has no effect on GABA. Inhibits high voltage activated (HVA) calcium channels
Adverse effects- dizziness, fatigue, drowsiness, ataxia, peripheral edema, nystagmus, tremor. Considered to be drug of abuse secondary to potential for euphoria
Topiramate (Topamax)
Indications- partial seizure or primary GTCS. 2nd line unless other comorbidities exist. FDA approved for migraines prophylaxis
Pharmacokinetics- 70% is excreted in the urine unchanged; remainder is extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Poorly bound to plasma proteins.
MOA- blocks sodium channels, increases GABA action
Adverse effects- sedation, mental dulling (word finding difficulties), kidney stones, weight loss, higher risk of teratogenesis
Anti-epileptics pregnancy category
All category C teratogens, except topiramate, carbamazepine, and valproic acid are category D.
Phenobarbital
Indications- partial or generalized onset. Typical second line to side effects, tolerance/dependence. 1st line in neonates*
Pharmacokinetics: metabolized by the liver, mainly through hydroxylation and glucuronidation. Half is protein bound in plasma
MOA- increased GABAa action
Adverse effects- sedation, tolerance, dependence, induction of cytochrome P450 enzymes, cardiorespiratory depression
Ethosuximide (Zarontin)
Indications- absence seizures only. First line for these (3Hz spike and wake on EEG). Doesn’t help/harm any other types.
Pharmacokinetics- metabolized by liver (CYP3A4, CYP2E1); low protein binding (<5%)
MOA- blocks thalamic T-type calcium channels
Adverse effects- GI distress, fatigue, headache, urticaria, Stevens Johnson syndrome
Vigabartrin (Sabril)
Indications- infantile spasms once ACTH/steroids fail. 2nd line for partial onset seizures.
Pharmacokinetics- not metabolized by the liver, renal excretion. No protein binding.
MOA- increases GABA by irreversibly inhibiting GABA transaminase
Adverse effects- blurred vision, confusion, depression, diplopia, fatigue, weight gain, ataxia, diarrhea, drowsiness, tremor, irritability. Can cause diffuse atrophy of retinal nerve fiber layer, resulting in irreversible peripheral vision loss, visual field testing suggests every 3 months.
*head drop and jerks of upper extremity in infants. Can be accompanied by loss of developmental milestones. Strange EEG. Can develop intellectual disability and intractable seizures.
