Anticonvulsants

4 classes of anticonvulsant MOA
	
	Voltage-gated Na channel blocker -> inhibit sustained firing
	Voltage-gated Ca channel blocker
	Reduce Glu synapse activity
	Enchance GABA synapse activity

Spectrum of action
	
	Generalized, focal motor, partial seizures: Rx w/ carbamazepine, phenytoin, valproic acid, lamotrigine, phenobarbital
	Generalized absence seizures: Rx w/ ethosuximide, valproic acid, lamotrigine, but NOT carbamazepine
	Complex childhood seizures: Rx w/ benzodiazepine, valproic acid, or unusual Rx (eg ketogenic diet, ACTH)

Status epilepticus therapy
	
	1. Airway, breathinq, circ support
	2. IV glucose
	3. IV benzodiazepine (lorazepam or diazepam) (possible coma side effect and need for mech vent)
	4. IV phenytoin or fosphenytoin (slow admin to avoid bradycardia and arrhythmia)
	5. IV phenobarbital
	6. Midazolam or general anesthesia

General side effects of anticonvulsants
	
	Teratogenic, spina bifida, antagnoizes folic acid
	Induces metabolism of birth control pills
	Altered endogenous hormone metabolism, ovarian dysfunction
	May inc O2 free radicals
	Dec epoxide hydrolase activity -> less oxidative detox of anticonvulsant metabolites

Phenobarbital
	
	MOA: barbiturate (inc GABA/BZ receptor function)
	PK: long t1/2, liver metabolism to active metabolites
	Tox: cognitive dulling, behavioral side effects

Mysoline
	
	MOA: prodrug of phenobarbital and PEMA -> barbiturate effects
	PK: long t1/2, liver metabolism to active metabolites
	Tox: cognitive dulling, behavioral side effects

Phenytoin
	
	MOA: voltage-gated Na channel blocker -> inhibits sustained repetitive firinq
	PK: saturable liver metabolism
	Tox: little sedation, at high levels causes ataxia and nystagmus, "purple glove", gum hypertrophy, hirsutism

Fosphenytoin
	
	Prodrug of phenytoin w/o as much peripheral side effects

Carbamazepine
	
	MOA: voltage-gated Na channel blocker -> inhibits sustained repetitive firinq
	Makes generalized absence seizures worse
	PK: sustained release extends short t1/2

Valproic acid
	
	MOA: Na channel blocker, enhance GABA/BZ receptors, ?other mechanisms
	Rx all types of seizures
	Tox: fatal hepatic necrosis in children <2yo esp if on a 2nd anticonvulsant, few cognitive side effects

Lamotrigine
	
	MOA: blocks Na channels assoc w/ presynaptic Glu release
	PK: other drugs like valproic acid prolong t1/2
	Tox: few cognitive side effects, severe skin rash

Benzodiazepine
	
	MOA: enhance GABA/BZ receptor function
	1st line Rx for status epilepticus

Reference flash card
	
	Barbituate -> Enhance GABA/BZ receptor
	Benzodiazepine -> Enhance GABA/BZ receptor
	Carbamazepine -> Blocks Na channel
	Ethosuximide -> Blocks Ca channel
	Lamotrigine -> Blocks Na channel
	Phenytoin -> Blocks Na channel
	Tiagabine -> Blocks GABA reuptake
	Topiramate -> Blocks Glu receptor and Na channel
	Valproic acid -> Blocks Na channel, enhances GABA receptor
	Vigabatrin -> Blocks GABA breakdown