Unit 3-Antiepileptics Flashcards
Phenytoin
Drug class
Voltage-gated Na channel stabilizer
Phenytoin
Mechanism
Stabilize inactive conformation of Na channel
Phenytoin
Uses
Less effective for absence (particular pediatric), myoclonic, atonic seizures
IV route useful for status epilepticus
Phenytoin
Side effects
- Rash, gingival hyperplasia, hirsutism, lupus-like reaction;
- can cause contraceptive failure
- Mild myelosuppression, increased LFT;
- long-term: cerebellar degeneration, peripheral neuropathy, osteoporosis
- IV infusion limited by hypotension;
- hepatic enzyme inducer (both auto- and hetero-inducer), highly protein bound
Carbamazepine
Drug class
Voltage-gated Na channel stabilizer
Carbamazepine
Mechanism
Stabilize inactive conformation of Na channel
Carbamazepine
Uses
- More effective for complex partial seizure than primary generalized;
- bipolar disorder;
- neuropathic pain
Carbamazepine
Side effects
- Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs;
- can cause contraceptive failure
- Hepatic enzyme inducer (both auto- and hetero-inducer); highly protein bound; must increase dose in 1-2 wks due to autoinduction; side effects likely due to epoxide metabolite
Oxcarbamazepine
Drug class
Voltage-gated Na channel stabilizer
Oxcarbamazepine
Mechanism
Stabilize inactive conformation of Na channel
Oxcarbamazepine
Uses
- More effective for complex partial seizure than primary generalized;
- bipolar disorder;
- neuropathic pain
Oxcarbamazepine
Side effects
- Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs;
- can cause contraceptive failure
- Designed to bypass carbamazepine epoxide;
- less protein-bound, less autoinduction, fewer interactions, less toxic, longer half-life than carbamazepine
Lamotrigine
Drug class
Voltage-gated Na channel stabilizer
Lamotrigine
Mechanism
Stabilize inactive conformation of Na channel
Lamotrigine
Uses
- Primary generalized epilepsies, absence seizures;
- indicated in children;
- bipolar disorder;
- neuropathic pain
Lamotrigine
Side effects
- Rash, (rarely, Stevens-Johnson):
- slow initial titration important;
- may lead to contraceptive failure
- May exacerbate myoclonic seizures;
- competes with valproic acid for excretion (potential synergy);
- hepatic enzyme inducer;
- not very protein bound
Valproate
Mechanism
Unknown; likely affects Na-gated channels and GABA system
Valproate
Uses
- Broad spectrum: absence, myoclonic, tonic-clonic, primary generalized, partial onset, and secondary generalized seizures (but not absence seizures);
- IV for status epilepticus;
- bipolar treatment, migraine and long-term cluster headache prophylaxis
Valproate
Side effects
Weight gain, hair turnover, hyperammonemia (which can be mitigated with oral carnitine), teratogenicity, blood dyscrasias
Pancreatitis
Vigabatrin
Drug class
GABAergic anti-epileptic
Vigabatrin
Mechanism
GABA transaminase binder (slows down intracellular breakdown of GABA)
Works on GABA-A
Vigabatrin
Uses
Anti-epileptic
Tigabine
Drug class
GABAergic anti-epileptic
Tigabine
Mechanism
GABA reuptake inhibitor
Works on GABA-A
Tigabine
Uses
Anti-epileptic
Benzodiazapines
Uses
GABAergic anti-epileptic
Benzodiazapines
Mechanism
Bind GABA-A
Benzodiazapines
Uses
Status epilepticus (refractory); anesthesia
Benzodiazapines
Side effects
Sedation
Long-term usefulness limited by tolerance
Gabapentin
Drug class
GABA analog
Gabapentin
Mechanism
Block presynaptic influx of Ca
Gabapentin
Uses
- Adjunct for partial complex epilepsy;
- more commonly used for neuropathic pain
Gabapentin
Side effects
Sedation
Absorption limited by intestinal AA transporter (there is a Tm); limited protein binding; no metabolism or drug interaction in humans (so few side effects)
Pregabalin
Drug class
GABA analog
Pregabalin
Mechanism
Block presynaptic influx of Ca
Pregabalin
Uses
- Adjunct for partial complex epilepsy;
- more commonly used for neuropathic pain
Topiramate
Drug class
Glutamate Receptor Blockers
Topiramate
Mechanism
- Partial AMPA, Kainate Ca receptor blocker
- secondary effect at voltage-gated Na channel, GABA system
Topiramate
Uses
- Partial onset seizures, secondary generalized seizures, primary generalized epilepsy;
- migraine prevention, long-term prevention of cluster headaches
Topiramate
Side effects
Mild metabolic acidosis, kidney stones (due to some carbonic anhydrase activity); modest weight loss; rare acute glaucoma; sedation
Word-finding problems
Carbonic anhydrase activity leads to mild metabolic acidosis, which leads to respiratory compensation, which leads to mild alkalosis, which leads to calcium ionization, which leads to tingling; treat with vitamin C (acidify urine)
Felbamate
Drug class
Glutamate Receptor Blockers
Felbamate
Mechanism
NMDA receptor blocker; secondary effect at voltage-gated Na and Ca channels, GABA system
Felbamate
Uses
Partial onset seizures with or without secondary generalization; medically refractory epilepsy
Felbamate
Side effects
Uncommon but potentially fatal. Aplastic anemia, acute hepatic failure. Requires monitoring.
Levetiracetem
Drug class
Synaptic vesicle binder
Levetiracetem
Mechanism
Binds synaptic vesicle protein 2, leading to less NT release
Levetiracetem
Uses
Partial onset seizures, secondary generalized seizures; maybe primary generalized epilepsy
Levetiracetem
Side effects
Well tolerated; sedation, mostly; rarely, irritability, aphasia, thrombocytopenia
Ethosuximide
Drug class
Voltage-gated Ca channel blocker
Ethosuximide
Mechanism
Blocks T-type Ca-channels in thalamo-cortical circuits
Readily absorbed, minimal first pass metabolism; not protein bound
Ethosuximide
Uses
Absence seizures only (and neuropathic pain)
Ethosuximide
Side effects
Nausea (transient), sedation, irritability
