Epilepsy Part 2

Indications
Broad Spectrum Agent
Complex Partial Seizures
Absence seizures
Bipolar Disorder
Migraine Prophylaxis

MOA
Modulate sodium channels

Teratogenic

most effective AED for generalized tonic-clonic seizures

50-150 mg/L

• Hepatic metabolism (potent inhibitor and highly protein bound)
• VPA: decreases the PHT total, CBZ total, TPM and TGB (small amount)
• VPA: increases the PHT unbound, CBZ unbound, CBZ epoxide, PB, felbamate, LTG,
ethosuximide, tiagabine unbound, ZNS
• Inducers (CBZ, PHT, PB) decrease VPA concentrations

a slight dose increase due to bioavailability differences

MOA: fast sodium channel blocker
• CI: TCA or CBZ sensitivity/allergy, history of bone marrow suppression, concomitant nefazodone

Boxed Warnings:
•SJS/TEN: 10-fold increase risk in individuals of Asian descent (test for HLA-B*1502
allele)
•Aplastic anemia/agranulocytosis: periodic CBC & d/c if evidence of bone
marrow suppression and/or WBC or ANC < 3000/mm3 or 1500/mm3, respectively
•Drug reaction with eosinophilic and systemic symptoms (DRESS) and
multiorgan hypersensitivity

• Idiosyncratic ADRs: hyponatremia, SIADH, cardiac disturbances, osteoporosis
• Dose-related ADRs: diplopia, drowsiness, nausea, sedation
• Monitoring: LFTs, CBC, CMP, CBZ levels

• MOA: fast sodium channel blocker
• CI: hypersensitivity to OXB or eslicarbazepine

Warnings/precautions:
•Blood dyscrasias
•SJS/TEN - see CBZ
•DRESS and multiorgan hypersensitivity
•Cross hypersensitivity with CBZ
•Hyponatremia (more severe than CBZ)

• Dose-related ADRs: nausea, headache, CNS related
• Monitoring: LFTs, CBC, CMP

• MOA: sodium channel blocker
• CI: hypersensitivity to PHT or hydantoins, history of PHT-induced hepatotoxicity,
coadministration with delavirdine, IV administration in patients with bradycardia, sinoatrial block, second or third degree AV block, or Adams-Strokes syndrome

• Boxed Warning: cardiovascular events with IV infusion > 50 mg/minute

Warnings/precautions:
•Blood dyscrasias
•SJS/TEN - see CBZ
•DRESS and multiorgan hypersensitivity
•Local toxicity w/ IV use (e.g., purple glove syndrome)
•Hepatic injury
•Exacerbation of porphyria
•Renal or hepatic impairment, hypoalbuminemia, hyperglycemia
•Teratogenic

• MOA: enhances GABA evoked chloride channels
• CI: hypersensitivity to barbiturates, personal or FH of acute intermittent porphyria, impaired
hepatic function, respiratory disease with obstruction or dyspnea, substance abuse

Warnings/precautions:
•SJS/TEN
•CNS depression
•Paradoxical stimulatory response (children)
•Respiratory depression
•Habit forming (Schedule IV)
• CNS ADRs: somnolence, confusion, cognitive impairment
• Dose-related ADRs: HTN, respiratory depression, coma
• Idiosyncratic: decrease bone mineral density (chronic use)

• Monitoring: CBC, CMP, PB levels (target level = 10-40 mcg/mL)

• MOA: unknown; binds SV2A and inhibits presynaptic calcium channels
• CI: hypersensitivity to levetiracetam; angioedema and anaphylaxis

Warnings/precautions:
•Blood dyscrasias
•SJS/TEN
•CNS depression
•Angioedema and anaphylaxis
•Psychiatric symptoms – psychosis, aggression, anger

• CNS ADRs: drowsiness, ataxia
• Dose-related ADRs: nausea, headache
• Idiosyncratic: cognitive and mood changes, depression, irritability

• Monitoring: CBC, CMP

• MOA: blocks sodium and calcium channels, decreased glutamate release
• CI: history of hypersensitivity with other AEDs

Warnings/precautions:
• Blood dyscrasias
• SJS/TEN - typically within 2-8 weeks of initiation
• DRESS
• Phenylketonurics (phenylalanine found in tabs and oral suspension)
• Hemophagocytic lymphohistiocytosis (HLH)
• Aseptic meningitis
• Binding in eye and other melanin-containing tissue
• False (+) for PCP

• MOA: blocks sodium, T-type calcium channels, and increased dopamine
• CI: hypersensitivity to zonisamide, sulfa allergy

Warnings/precautions:
• DRESS
• Metabolic acidosis
• Nephrolithiasis
• Oligohydrosis and hyperthermia (children)
• Renal dysfunction
• Sulfonamide reactions
• Cognitive/neuropsychiatric effects (cognitive dulling, confusion, psychomotor
slowing, depression, psychosis)

• MOA: blocks sodium channels, enhances GABA neurotransmission, inhibits carbonic anhydrase,
blocks AMPA/kinase subtypes of glutamate receptors

Warnings/precautions:
• Metabolic acidosis
• Nephrolithiasis
• Oligohydrosis and hyperthermia
• Cognitive/neuropsychiatric effects (cognitive dulling, confusion, psychomotor slowing, depression, psychosis)
• Acute myopia and secondary angle-closure glaucoma
• Visual field defects
• Hyperammonemia and encephalopathy
• Hypothermia w/ VPA
• Teratogenic

• MOA: inhibition of alpha-2-delta subunit of voltage-dependent calcium channels
• CI: hypersensitivity to GBP

Warnings/precautions:
• DRESS
• Neuropsychiatric ADRs in pediatric patients (age 3-12 yo)
• Tumorigenic potential
• CNS-related ADRs: dizziness, somnolence, ataxia
• Concentration-related ADRs: drowsiness, sedation
• Idiosyncratic ADRs: peripheral edema, weight gain

• No CYP450 interactions

• MOA: inhibition of alpha-2-delta subunit of voltage-dependent calcium channels
• CI: hypersensitivity to pregabalin, angioedema and hypersensitivity reactions

Warnings/precautions:
• SJS/TEN
• Angioedema
• Dizziness/somnolence
• Peripheral edema
• Thrombocytopenia/decreased platelet count
• Prolonger PR interval
• Rhabdomyolysis
• Weight gain
• Tumorigenic potential
• Ophthalmologic effects