Seizures Flashcards
First line for focal seizures
Lamotrigine
First line for generalized seizures
Valproate - unless pregnant!!
Gabapentin PK
Requires active transport
Limit to 1,200mg per dose b/c saturable
Main clinically significant interaction PK interaction in terms of absorption
Phenytoin and enteric feeding
Drugs clinically important in terms of protein binding (>90%):
Phenytoin* Valproate Diazepam Tiagabine Perampanel
Why should you check phenytoin levels regularly?
Narrow therapeutic range, but also…
accumulation leads to rapid serum level changes even with small dose adjustments within the therapeutic window.
Why should you check carbamazepine levels regularly upon initiation?
Autoinduction: levels will be higher within first week or so than they will after that, as autoinduction increases it’s metabolism.
What is the the main route of metabolism of AEDs?
Oxidation by Cytochromes.
- Most notable: 2C9, 2C19, and 3A4.
Possible clinical scenarios with AEDs and other drugs:
Adding inducer-AED to statins; decrease statin.
Adding new med to inducer-AED; ineffective birth control.
Removal of inducer: warfarin goes nuts.
Inducer/inhibitor timing
Inducers = slow to take effect Inhibitors = rapid effects
Broad spectrum inducers
CBZ
Phenytoin
Phenobarbital/Primidone
Selective 3A4 inducers
Felbamate
Topiramate
Oxcarbazepine
Eslicarbazepine
UGTs involved in AED metabolism
UGT1A9 - valproate
UGT2B7 - valproate and lorazepam
UGT1A4 - lamotrigine
Inhibitors
Valproate - UGT and 2C19
Topiramate/Oxcarbazepine - 2C19
Felbamate - 2C19
AEDs that are renally cleared
Gabapentin Pregabalin Levetiracetam Lacosamide (1/2) Eslicarbazepine (1/2)
AED most related to rash-like SE’s:
Lamotrigine!
Most common SE of AEDs
Neurologic/Psychiatric effects
- sedation, unsteadiness, tremor, vission problems, etc.
Less common SEs of AEDs
GI - valproic acid
Lab changes
- hyponatremia - carbamazepine and related
- Increase LFTs
- Leukopenia - carbamazepine
- Thrombocytopenia - valproate
Weight gain - valproate, gaba/pregaba, CBZ a little
Weight loss - felbamate, zinisamide?, topiramate
Aplastic anemia / agranulocytosis AED SE with:
Felbamate
Hepatic failure AED SE with:
Felbamate
Neuropathy / Cerebellar syndrome AED SE with:
Phenytoin
Facial coarsening, hirsutism, gingival hyperplasia with:
Phenytoin
Treatment recommendations for the elderly:
Use the new drugs
Focus on tolerability
Lamotrigine a good option
Treatment recommendations for kids:
Avoid valproate - hepatotoxicity
Avoid lamotrigine - rash
May need higher doses b/c of rapid metabolism
Treatment recommendations for women:
Caution inducers with oral contraceptives.
Teratogenicity a problem.
- All drugs class C or D, but may need them.
Breastfeeding - okay!
- Except barbiturates and benzos
Bone Health - can be a problem
- Switch to lamotrigine
Status Epilepticus in general
Massive seizure, can leave permanent deficits.
Treat early and aggressively with IV AEDs.
Begin treatment if seizure duration persists > 5 minutes
FDA approved therapy for home treatment of Status Epilepticus:
Rectal diazepam gel - really just for kids
Status Epilepticus treatment
Step 1 - IV lorazepam
Step 2 - IV phenytoin/fosphenytoin
If refractory - IV midazolam or propofol
