Anticonvulsants
Name
Phenybarbital
Categories
Traditional
Partial
IV & PO (susp)
Mechanism of Action
- Blocks Na+ channels (KA)
- Facilitates GABA
- modulates Glutamate
Metabolism
- Hepatic
- P450 inducer/substrate
- ½ life: 3-7 days
Drug Interaction
- Phenytoin ↑ then ↓
- Warfarin, Chloramphenicol, ↓
- VPA makes phenobarb ↑
Uses
- Neonatal
- Status Epilepticus
- Other refractory epilepsies
Phenytoin
Aka Dilantin
Traditional
Partial
IV & PO (susp)
- Blocks Na+ channels
(NMDA)
- Hepatically metabolized/enzyme
inducer
- Poorly absorbed in infants
- Zero-order kinetics
- 90% Protein Bound
- Warfarin ↑ then ↓
- Carbamazepine ↓
- Phenytoin goes ↑
- ↑ with cimetidine, isomiazide
- Complex interaction with VPA, salicylic
acid, thyroxine, NSAIDS, and warfarin
- Status Epilepticus
- Acute/Subacute
Symptomatic Seizures
- Any “partial epilepsy”
Carbamazepine
Aka Tegretol
Traditional
Partial
PO (susp)
- Blocks Na+ channels
(NMDA)
- Hepatically metabolized/enzyme
inducer and substrate
- Autoinduction
Carbamazepine:
- ↓ phenytoin, phenobarb, VPA, clonazepam,
and non AEDs
- ↑ by cimetidine, propoxyphene, iosmiazid,
macrolide antibiotics
- Any “partial epilepsy”,
especially in children
Oxcarbazepine
Aka Trileptal
New
Partial
PO (susp)
- Blocks Na+ channels
DR - same as above
I - only rash (25% cross reactivity with above)
no heme or liver side effects
Ch r- none known
New
Partial
PO (soln)
Unknown mechanism of action
- Evidence suggests that it
enhances gabanergic activity
- less effect on hepatically metabolized drugs
- Although ↓ lamotrigine by induction of
glucuronidation
- ↑ phenytoin and phenobarb by inhibiting
CYP2C19
- Can lower contraceptive levels
- Almost no drug interactions
- Any “partial epilepsy”,
especially in children
Gabapentin
Aka Neurontin
- Very similar to CBZ, but not
converted to epoxide metabolite
which is thought to account for
many adverse effects.
- Only a very weak p450 inducer
(i.e. less auto induction)
- Excreted unchanged by kidneys
New
Partial
PO (soln)
Unknown mechanism of action
- Evidence suggests that it
enhances gabanergic activity
- Excreted unchanged by kidneys
- Almost no drug interactions
Tiagabine
Aka Gabatril
New
Partial
PO (tabs only)
- Inhibits the reuptake of
GABA
- Hepatically metabolized
- No significant effect on steady states of other
AEDs
- VPA can displace Taigabine from albumin,
resulting in an ↑ free fraction.
Therefore, titrate slower if patient on VPA.
DR - sedation, dizziness, ataxia
I - wt. gain, peripheral edema, behavioral
changes
Chr - none yet
DR - sedation, dizziness, ataxia
I - wt. gain, peripheral edema, behavioral
changes, visual disturbance
Chr – none yet
DR - dizziness, somnolence, nausea, cognitive
slowing
I - rash, mood change, generalized
nonconvulsive status
Chr - none known
Often used in
Neuropathic pain
Lyrica
- Considered wimpy &
usually only used as add on
therapy for partial complex
seizures / pain
- Considered wimpy &
usually only used as add on
therapy for partial complex
seizures / pain
Any partial epilepsy
Valproic Acid
Divalproex
Sodium
Depakene
Depakote
Traditional
Broad spectrum
PO (sprinkles) &
IV
- Blocks Na+ channels
- ↑ brain levels of GABA (both
inhibits breakdown enzymes
and stimulates synthesis)
- Hepatic Metabolism
- Enzyme Inhibitor
- Also competes for protein
binding sites
- ↑ with salicylates and cimetidine
- ↓ with phenytoin, phenobarb, carbamazapine,
and lamotrigine
- Can ↑ the levels of phenobarb and
lamotrigine
Broad spectrum, essentially
used for everything
Lamotrigine
Lamictal
New
Broad spectrum
PO (chew tab)
- Blocks Na+ channels
- Inhibits release of glutamate
- Hepatically metabolized
- Mild Inducer for glucuronidation
- mildly ↓ VPA levels
- Lamotrigine levels are ↓ by enzyme inducers
(phenytoin, phenobarb, carbamazapine)
- ↑ by VPA
- OCs can ↓ Lamotrigine levels
- Broad spectrum
- Some evidence to support
use in primary generalized
epilepsy
Topiramate
Topamax
New
Broad spectrum
PO (sprinkles)
- Blocks Na+ channels
- Inhibition of kainite and
AMPA glutamate receptors
- Both Hepatic (25%) & Renal -Metabolism (75%)
- Does not significantly effect other AEDs
- OCs may be ineffective
- levels ↓ with inducers (phenytoin,
carbamazepine, and Phenobarbital)
Broad spectrum
-Therapeutic levels
50-100
-Neural Tube Defects
-Used for migraine
prophalaxis &
Bipolar Disorder
-Therapeutic range
not established
-Seems it may be
safe in pregnancy
-Relatively
nonsedating
-Used in weight loss
-Teratogenicity not
well established
Levetiracetum
Keppra
New
Broad spectrum
PO
New
Broad spectrum
PO
- Completely Unknown
- Renally excreted
- Pretty much no drug interaction
Broad spectrum
- Blocks Na+ channels
- Hepatic Metabolism
Sulfonimide
- Clearance may be ↑ by enzyme inducing
AEDs
Broad spectrum
Old
Narrow spectrum
PO (syrup)
- Blocks T-type Ca2+ channels
- Hepatic
- Inhibits enzymes
- VPA levels may ↑ when 2 are used
concomitantly
Absence
DR - GI distress, anorexia, tremor, Down plts
I - pancreatitis, hepatic failure (especially in
kids on polypharmacy), stupor, coma,
depression, rash, hyperammonemia,
thrombocytopenia, Parkinsonism
Chr - Wt. gain, hair loss, ? Polycystic ovaries
DR - dizziness, ataxia, drowsiness, insomnia
I - rash(SJS) (1/1000 adults, 1/50 kids. Risk ↑
with VPA, also other hypersentivity reactions
including risk of hepatic or renal failure, DIC,
arthritis
Chr - none
DR - cognitive slowing, word finding
difficulties, parasthesias, metabolic acidosis,
dizziness
I - rash, GI, glaucoma, irritability, hypohidrosis
(mostly children)
Chr - renal stones (1-2%), wt. loss
DR - sedation, dizziness
I - GI intolerance, depression, irritability
Chr - none
DR - fatigue, confusion, dizziness
I - sulfa rxns (SJS, hepatic necrosis),
hypohidrosis, hyperthermia (kids)
Chr - Renal Stones
DR - sedation, headache
I - rash, psychiatric decompensation, GI upset,
lupus-like syndrome
Zonisamide
Zonegran
Ethosuximide
Side Effects
DR - sedation, cognitive impairment
I - rash, hyperactivity, hepatic failure, aplastic
anemia
Chr - osteoporosis, frozen shoulder,
permanent IQ impairment
DR - dizziness, diplopia, nausea
Rapid Infusion - venous irritation, necrosis,
hypotension, and arrhythmias
I - rash(SJS), blood dyscrasias, hepatic failure,
lupus-like syndrome
Chr - neuropathy, gingival hyperplasia,
hirsutism, osteopenia, altered facial features,
cerebellar degeneration
DR - dizziness, diplopia, sedation,
↓ WBCs and Na+, bradyarrhythmias (elderly)
I - rash(SJS), aplastic anemia, hepatic
failure,pancreatitis, lupus-like syndrome
Chr - osteopenia
Misc.
-Very inexpensive
-Known teratogen
-Ther. Range: 10-40
-Cheap
-Known teratogen
-Ther. Range: 10-20
-Titrate slowly
-Also useful for
bipolar & trigeminal
neuralgia
-Neural Tube defects
-Levels 4-12
-Doses very rapidly
-Teratogenicity may
be better
(theoretically)
-Often used in
Neuropathic pain
-Indication for
fibromyalgia
-May have
antianxiety/analgesic
effect
-Teratogenicity in lab
animals
Teratogenicity not
well established
-Must be slowly
titrated
-Teratogenicity not
well established
Range 40-100