ClinMed Exam 6: Anti-Epileptic Medications

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T/F: Seizures are caused by overactivity of electrical activity of the brain (excess glutamate) so almost all drugs to treat epilepsy/seizures will cause lethargy, ataxia, dizziness, or sedative symptoms.
hold tube feeding for 1 hour before and after giving phenytoin
For patients on continuous enteral tube feedings, you should hold tube feedings for ___ hour(s) before and after administering what drug?
phenytoin
- non-linear (dose and concentration dont change at same rate)
_____ has a a non-linear pharmacokinetic profile, as little dose changes can cause big changes to the concentration, rather than the dose and concentration of drug changing at same rate.
phenytoin
- metabolized by the liver
- enzyme inducer (speeds up metabolism of other drugs metabolized by the liver, therefore: decreasing [ ] of other drugs)
- non-linear
Phenytoin is metabolized by the _______. Due to this it is considered a enzyme _______. how does this change the concentration of other drugs?
goal therapeutic range (to limit ADR):
-total phenytoin: 10-20 mcg/mL
-free phenytoin: 1-2 mcg/mL (10% of total)

phenytoin should be infused SLOWLY
-if infused too fast it will cause HOTN and bradycardia
The therapeutic range for phenytoin (to limit ADR):
- total phenytoin: ______ mcg/mL
- free phenytoin: ______ mcg/mL

phenytoin should be infused ____ (slowly/quickly) to avoid HOTN and bradycardia.
concentration dependent: (keeping therapeutic range limits these)
- nystagmus
- behavioral changes

idiosyncratic:
- hirsutism
- gingival hyperplasia
- rash
- hepatotoxicity
- folate deficiency
- metabolic bone disease (may need vitamin D supplements)
What are the unique concentration dependent and idiosyncratic (can occur at anytime) ADR for phenytoin?
fosphenytoin is same as phenytoin except it can be infused faster than phenytoin (good for acute/emergent seizures since drug gets to pt faster)
- also fosphenytoin is IV only
What is the difference between fosphenytoin and phenytoin?
valproic acid:
- metabolized by liver
- potent ennzyme inhibitor
- carbapenems can decrease [ ] of valproic acid (and cause seizures) so avoid this antibiotic class
this drug is metabolized by the liver and is a POTENT enzyme inhibitor (increases [ ] of other drugs metabolized by liver). Carbapenems should be avoided in patients on this drug since they may _____ the concentration of the drug.
BBW:
- acute hepatic failure
- acute pancreatitis
- NTD in pregnancy (avoid in pregnancy)

other ADR (not BBW):
- weight gain
- hyperammonemia (can lead to encephalopathy)
What are the BBW of valproic acid? What are some other important ADR?
carbamazepine
- autoinducer (and enzyme inducer)
This drug has autoinduction, meaning it induces its own metabolism (and decreases the [ ] of itself) for the first 20-30 days. Therefore you have to increase the dose frequently for the first few weeks. It is also an enzyme inducer for other drugs.
BBW: - SJS - aplastic anemia ADR: - neutropenia (bone marrow suppression) - skin rash - hepatotoxicity - hyponatremia (SIADH)What are the BBW for carbamazepine? What other unique idiosyncratic ADR does this drug have?carbamazepine - cant be used in emergent/acute seizures (no IV)This drug has no IV form, and therefore cannot be used in emergent/acute seizures. It has a BBW for SJS and aplastic anemia.oxcarbazepine does not have autoinduction (easier to dose) oxcarbazepine is also an enzyme inducer but much less than carbamazepineWhat is the difference between oxcarbazepine and carbamazepine?levetiracetam - few ADR or interactions (not metabolized by liver) - best drug for seizures (besides absence) levetiracetam can cause behavioral disturbances (can be profound) but otherwise does not have any notable side effectsthis is the #1 drug for seizures (besides absence seizures) because it is not metabolized by liver so it does not have very many ADR/interactions. What ADR does it have?phenobarbital - #1 drug for neonatal seizures - potent enzyme inducer to liver metabolized drugs ADR: - sedation/ataxia (adults, like most other seizure drugs) - hyperactivity (children) - can also cause rash and blood dyscrasia (low WBC or RBC)this is the drug of choice for neonatal seizures, but it can also be used for refractory status epilepticus or alcohol withdrawal seizures. What ADR reactions does this drug have and how does it differ for adults vs children? What drug interactions does it have?gabapentin and pregabalin - well tolerated and few interactions (not metabolized) - adjunct for focal seizures if fails first lineThis drug is used as an adjunctive agent for patients with focal seizures who have failed initial treatment, since they are not metabolized and have few drug interactions and are well tolerated.lamotrigine: - extensively metabolized by liver so valproic acid can inhibit its metabolism (which may increase changes of BBW SJS occurring)the metabolism of this drug can be inhibited (increased [ ]) when used with valproic acid. it has a BBW for SJS (esp. when used with valproic acid)lamotrigine should not be taken with valproic acid - valproic acid is enzyme inhibitor so it can drastically increase lamotrigene [ ] - this increases risk for lamotrigine's BBW SJSSince lamotrigine is extensively metabolized by the liver, what drug should it never be taken with and why?topiramate: - difficulty concentrating, psychomotor slowing, speech difficulties - peripheral neuropathy, kidney stonesthis drug causes difficulty concentrating, psychomotor slowing, and speech/language difficulties. What other ADR does it have?lacosamide - may increase PR interval (EKG at baseline) - unique MOA - only used as adjunct tx of focal seizures very expensivethis drug has a unique MOA but it may cause an increased PR interval so you should do baseline EKG. What is it used for?clobazam - benzo derivative (CNS depressant side effects) - can cause seizure, tremor, hallucinations/psychosis, or anxiety if stopped abruptly. - adjunct therapy for seizures associated with lennox-gastaut syndromeThis seizure medication is a benzodiazepine derivative so it can cause CNS depressant side effects and seizures, hallucinations, tremor, or anxiety if stopped abruptly.vigabatrin - prescriber restrictions (SHARE program) due to risk of vision lossThis seizure medication has prescriber restrictions (must be in enrolled in SHARE program) due to the risk for _______BBW - hepatic failure, aplastic anemiaWhat are the BBW for felbamate?seizure lasting 5+ minutes - initial tx: benzo (lorazepam IV or diazepam IV) - diazepam has quicker onset but less duration (15-30 min), while lorazepam has slightly slower onset but longer duration (12-24hr) if after 20+ minutes still having seizure: - give IV levetiracetam - could also use IV valproic acid or IV fosphenytoinWhat is the inital treatment for status epilepticus? What if the seizure continues, and is ongoing for 20+ minutes?- bupropion (antidepressant) - carbapenems (atb) - amphetamines/cocaine - AP (clozapine, heloperidol, phenothiazides, etc.) - tramadolWhat are some of the most common drugs to lower the seizure threshold?see treatment algorithm in notes