ANTICONVULSANTS

Drug MOA Uses Adverse Effects Drug Interactions/Other

Cosmetic effects:
• Hirsutism
• Coarse faces
• Acne
**P450 Inducer**
• Gingival hyperplasia
Difficult status epilepticus Vitamin/Hormone Depletions:
Phenytoin Na+ Channel ↓Phenobarbital levels
(Dilantin) (Phenytek) Blocker • Folate (Vit. B9)
↓Warfarin levels
NO effect →Megaloblastic anemia
Infantile spasms • Vitamin K Can cause increase in these
Absence seizures • Thyroxine (T4) if phenytoin is discontinued
Other:
• Extravasion injury with
injection
Short term control of Cosmetic effects:
Status epilepticus • Hirsutism
Gen. Tonic-clonic seizures • Coarse faces
Seizure prophylaxis for sx
• Acne **P450 Inducer**
(post-trauma, pre-neurosurgery)
• Gingival hyperplasia
Vitamin/Hormone Depletions: ↓Phenobarbital levels
Fosphenytoin Na+ Channel NO effect
(prodrug of pheytoin) Blocker Infantile spasms • Folate (Vit. B9) ↓Warfarin levels
Absence seizures →Megaloblastic anemia
• Vitamin K Can cause increase in these
• Thyroxine (T4) if Fosphenytoin is
Only IV
Other: discontinued
More water soluble then
phenytoin so no propylene glycol • NO Extravasion injury with
(NO extravasion), lower pH injection

Indication
Mild leukopenia or hyponatremia **P450 Inducer**
Complex Partial seizures
Circulating TH may be decresed; CBZ metabolism affected by
Gen. Tonic-clonic seizures
Carbamazepine TSH remains normal many drugs
Na+ Channel Trigeminal neuralgia
Not used anymore; Other Uses:
Blocker
replaced by OxCBZ Contraindication Bipolar disorder
May EXACERBATE
Blood disorders Trigeminal neuralgia
Absence seizures
Liver disorders Diabetic neuropathy
Myoclonic seizures
Indications
Complex Partial seizures
Fewer side effects that CBZ & Other Uses:
Primary & Secondary Gen.
Na+ Channel Phenytoin Trigeminal neuralgia
Oxcarbazepine Tonic-clonic seizures
Blocker Shooting/lancinating
Can cause HYPOnatremia neuropathic pains
NO effect
Absence or Myoclonic seizures
Indications Severe hepatotoxicity (fatal)
Na+ Channel
Simple or complex partial GI distress **P450 Inhibitor**
Blocker
Primary Gen. Tonic-clonic Weight gain ↑Phenobarbital levels
Photosensitive epilepsy Teratogenesis (↓folate) →NTDs ↑Clorazepam levels
Ca2+ T-Type Channel
Valproic Acid Juvenile myoclonic epilepsy Tremor
Blocker
Transient hair loss Contraindications
Broad Spectrum PCOS, menstrual disturbances Pregnancy
↑GABA production
Absence seizures Bone loss Liver dx
↓GABA metabolism
Myoclonic, Atonic seizures Ankle swelling
Primary & Adjunct Therapy (Ages ≥2)
Simple & complex Partial seizures
Lennox-Gastaut Syndrome
Na+ Channel
Blocker Rash (SJS) Other Uses:
Lamotrigine Alternative Monotherapy (Adults)
Aseptic meningitis Bipolar disorder
Simple & complex Partial seizures
↓GLUT release
May EXACERBATE
Myoclonic seizures
 Adjunct Therapy (Ages ≥2) Psychomotor slowing, word-finding
Partial seizures difficulty, impaired concentration,
Topiramate levels ↓ by
Na+ Channel Primary gen. Tonic-clonic seizures interference with memory
CBZ, phenytoin,
Blocker Lennox-Gastaut Syndrome
phenobarbital
Topiramate ↑GABA receptor effects nervousness, paresthesias
↓Kainate GLUT receptor Contraindication Kidney stones
Other Use:
effects Hx kidney stones or renal dx Weight loss/anorexia
Migraine prophylaxis
(weak inhibitor of carbonic Hypohydrosis
anhydrase) Metabolic acidosis
Adjunct Therapy (Adults)
Na+ Channel
Partial seizures Hypohydrosis
Blocker Zonisamide ½ life cut in
Weight loss
Ca2+ T-Type Channel half by CBZ, phenytoin
Broad Spectrum Alt. to Valproate: Abnormal thinking
Zonisamide Inhibitor
Absence seizures (Gen. & atypical) Nervousness
Other Use:
Myoclonic Agitation
↑GABA effects Migraine prophylaxis
Infantile spasms Irritability
↑DA/5HT effects
Lennox-Gastaut
Na+ Channel
Lidocaine Status Epilepticus (last resort)
Blocker
Na+ Channel Block Binds Collapsin-response
Adjunct Therapy – Partial Seizures Dizziness, diplopia
Lacosamide & Neuroprotective mediator protein 2 →
Neuropathic pain Somnolence, headache
(disease modifying) neuron diff., axon growth

Enhance GABA
So enhance inhibition
Drug MOA Use Adverse effects Drug Interactions/Other
BARBITUATES
1st Line CNS Depression →
Infantile seizures Sedation
Status epilepticus Respiratory/CV
GABAA Allosteric Depression
Activators → ↑duration Second choice for
Phenobarbital **P450 Inducer**
of GABA Cl- channel Partial seizures Physical Dependence
opening Gen Tonic-clonic seizures → SHORT-TERM only
Other CNS depressants
Tolerance
Increase metabolism of
May EXACERBATE
Vitamin D & K levels
Absence seizures Agitation/confusion
(elderly)
Indication Phenytoin → increases
Partial seizures conversion of primidone
GABAA Allosteric ↑Hyperactivity/aggression
Gen Tonic-clonic seizures to phenobarbital
Primidone Activators → ↑duration (kids)
May control refactory gen tonic-clonic
(prodrug) of GABA Cl- channel
opening Acute intermittent
Contraindications porphyria
Hx of porphyria

BENZODIAZIPINE
Mostly for short term tx to get seizure under control

Intermittent use
GABAA Allosteric for control of seizure clusters
Diazepam
Activators → ↑frequency Status Epilepticus
of GABA Cl- channel opening
Pen injector or Can give rectally
CNS Depression →
GABAA Allosteric Acute Rx : Sedation,
Lorazepam
Activators → ↑frequency Status Epilepticus DOC** Hypotonia
of GABA Cl- channel opening More water soluble Dysarthria Contraindications
Muscle incoordination Narrow ancle glaucoma
Approved for Long-Term Therapy (clonazepam) Under 9 yo (diazepam)
GABAA Allosteric
Lennox-Gastaut, myoclonic, atonic, absence Physical Dependence
Clonazepam Activators → ↑frequency
of GABA Cl- channel opening seizures Tolerance OD Antidote:
(tolerance in 6 months) Behavioral disturbances Flumazenil
GABAA Allosteric (esp. kids)
Approved for Long-Term Therapy
Clorazepate Activators → ↑frequency
of GABA Cl- channel opening In combination for partial seizures

Status Epilepticus
GABAA Allosteric
Buccal formulation (for kids)
Miazolam Activators → ↑frequency
of GABA Cl- channel opening Nasal admin in trials
Used when Diazapam & Lorazepam don’t work
 Other GABA enhancers
GABA Reuptake Tiagabine blood levels ↓
Adjunct Therapy (≥12 yrs)
Inhibitor Asthenia by CBZ, phenytoin,
Partial seizures
Inhibits GABA Transporter 1 (weakness, lack of energy) phenobarbital
Tiagabine
(GAT-1)
May EXACERBATE
Reduces reuptake by Abdominal pain So Effects ↓
Absence seizures
neurons & glial cells

Ca2+ Channel Blockers

Drug MOA Use Adverse effects Drug Interactions/Other
Toxicity:
*DOC* Psychotic behavior
Parkinson-like symptoms
Thalamic T-type Ca2+ Absence Seizures Blood dyscrasias
Photophobia
Channel Blocker Persistent headaches
Ethosuximide
(reduces low threshold Ca2+ May EXACERBATE Anorexia
Half-life 2x longer in
Currents) Partial seizures Hiccups
adults vs. children (60 vs.
Tonic-clonic seizures Lupus-like syndromes
30 hrs)
Neuropathic pain
Diabetic neuropathy
Post-herpetic neuralgia
Selective α2δ1
V-G Ca2+ Channel Use to be Adjunct/Monotherapy:
Gabapentin
Blocker Partial Seizures Other Uses:
(↓Glut release) Secondary generalized Migraine prophylaxis
Bipolar disorder
May EXACERBATE Weight gain w/ankle edema
Myoclonic & Absence seizures Irritability Pregabalin = more
Neuropathic pain Behavioral problems in kids potent than gabapentin
Fibromyalgia (pregabalin) Has been associated w/ (better absorption)
movement disorders
FDA approved Parent drugs
Selective α2δ1 cleared unchanged
Adjunct/Monotherapy:
V-G Ca2+ Channel by kidney
Pregabalin Partial Seizures
Blocker
Secondary generalized
(↓Glut release)
NO effect on
Myoclonic, Absence or
primary generalized tonic-clonic seizures
OTHER
Unknown
Binds Synaptic Vesicle Adjunct (Adults)
Protein 2A → blocks Partial seizures
synaptic vesicle fusion Asthenia Low risk drug-drug
Levetiracetam Some Monotherapy success Infection interations
Blocks Ca2+ Channel N- Behavioral problems in kids Cleared by Renal system
current Contraindications
↑ intracellular Ca2+ Renal dysfunction
↑GABA release
Non-competitive FDA approved
AMPA receptor Partial seizures CI = Renal dysfunction
antagonist Secondary adjunct therapeutic
Weight gain
Preampanel Can be used with
Aggression & Hostility
(so ↓ Glutamates excitatory Contraindications Gabapentin for
effects by blocking glutamate Liver dx neuropathic pain
receptor) Renal impairment
Magnesium
Used for magnesium deficiency seizures
chloride
Paraldehyde Alcohol withdrawal seizures
 Type of Seizure Characteristics Drug of Choice
One body part/sense involved
Simple Partial
No loss of consciousness, No postictal confusion
Temporal lobes – change in mood, illusions, hallucinations
Complex
Meaningless behaviors
Partial
Impaired consciousness, Postictal confusion
Tonic-Clonic Tonic extension of extremities → Clonic rhythmic movements
(Generalized) Loss of consciousness, Prolonged postictal confusion
General, Brief, arrhythmic jerking movements (<1 sec) occurring in
Myoclonic
few minute long clusters
(Generalized)
NO loss of consciousness
Atonic “Drop” seizures (fall to floor)
(Generalized) Loss of consciousness
Absence Brief episodes of staring/blanking out
(Generalized) No postictal state

Summary [52-56]
Na channel drugs
• Phenytoin (Dilantin, Phenytek)
• Fosphenytoin (Cerebyx, Prodilantin)
• Cabamazepine (Tegretol, Carbatrol)
• Oxcarbazepine (Trileptal)
• Valproic Acid (Depakene, Depakote)
• Lamotrigine (Lamictal)
• Topiramate (Topamax)
• Zonisamide (Zonegran)
• Lidocaine

GABA drugs
• Barbituates
o Phenobarbital (Luminal)
o Pimidone (Mysoline)
• Benzodiazepines
o Diazepam (Valium)
o Lorazepam (Ativan)
o Clonazepam (Klonopin)
o Clorazepate (Tranxene-SD)
• Tiagabine (Gabitril)
• Valproic Acid (Depakene, Depakote)
• Topiramate (Topamax)
• Zonisamide (Zonegran)

Ca channel drugs
• Ethosuximide (Zarontin)
• Valproic Acid (Depakene, Depakote)
• Zonisamide (Zonegran)
• Gabapentin (Neurontin)
• Pregabalin (Lyrica)
• Levetiracetam (Keppra)

Other/ Unknown
• Lacosamide (Vimpat)
• Magnesium chloride
• Paraldehyde