AEDs

Question 1

Carbamazepine: mechanism

Answer 1

Binds to neuronal sodium channels to reduce sustained high-frequency repetitive firing of action potentials

Question 2

Carbamazepine: indication

Answer 2

Partial and secondarily generalized seizures

Question 3

Carbamazepine: dose

Answer 3

Start 400 mg/day in 2 divided doses
Maximum 1,600 mg/day
Several long-acting forms available

Question 4

Carbamazepine: side effects

Answer 4

• Dose-related
• Drowsiness, dizziness, ataxia, dyskinesias, and visual disturbance
• Rare: Severe idiosyncratic hematologic reactions of agranulocytosis and aplastic anemia
• Induces CYP-450 isoenzyme
• Consider screening for HLA-B*1502 allele in Asians as this is associated wtih marked increase in skin rash.

Question 5

Ethosuximide: mechanism

Answer 5

Decreases the bursting of thalamocortical neurons responsible for generation of 3 Hz spike-and-wave discharges via reduction of low threshold (T-type) calcium channel currents

Question 6

Ethosuximide: indications

Answer 6

Absence seizures

Question 7

Ethosuximide: dose

Answer 7

500 mg in 2 divided doses

May increase to 1,500 mg/day

Question 8

Ethosuximide: side effects

Answer 8

• Common: nausea, vomiting, weight loss, diarrhea, abdominal pain, constipation
• Serious: blood dyscrasias

Question 9

Fosphenytoin: dose

Answer 9

Loading dose of 15-20 mg phenytoin equivalents/kg

Can be administered in 100-150 mg PE/min

Question 10

Fosphenytoin: side effects

Answer 10

Risk of hypotension and cardiac dysfunction lower than for phenytoin

Question 11

Phenobarbital: mechanism

Answer 11

• Enhancement of GABA-mediated inhibitory synaptic transmission
• Voltage-regulated calcium ion channels
• Reduces glutamate-mediated excitation

Question 12

Phenobarbital: indication

Answer 12

All seizures except absences

Question 13

Phenobarbital: dose

Answer 13

1.5-4 mg/kg/day in daily doses

IV available

Question 14

Phenobarbital: side effects

Answer 14

• Common: sedation, drowsiness, hyperactivity, irritability, and insomnia
• Rare: cognitive impairment, depression, movement disorders, megaloblastic anemia, osteoporosis, connective tissue disorders, teratogenicity, and exacerbation of porphyria
• Induces CP-450 isoenzyme, resulting in drug-drug interactions

Question 15

Phenytoin: mechanism

Answer 15

• Rate-dependent inhibition of sodium channels
• Calmodulin and cyclic nucleotide 2nd messenger systems
• Inhibition of voltage-dependent neurotransmitter release at the synapse

Question 16

Phenytoin: indications

Answer 16

• Partial-onset seizures and generalized tonic-clonic seizures
• Limited efficacy in absence, myoclonic, or atonic seizures

Question 17

Phenytoin: dose

Answer 17

Start 200-300 mg in 3 divided doses
Increase until maintenance dose reached (300-400 mg daily)
Loading dose of 1,000 mg may be given in 3 divided dose in 2 hour intervals or by IV

Question 18

Phenytoin: side effects

Answer 18

• Common: nystagmus, blurred vision, ataxia, slurred speech, gingival hypertrophy, hirsutism
• Long-term use: osteoporosis, peripheral neuropathy, cerebellar atrophy, gum hypertrophy
• Serious: purple glove syndrome

Question 19

Phenytoin: metabolism

Answer 19

Metabolized by CYP-450 system
Excretion by urine and feces
Conversion from 1st-order to Zero-order kinetics at levels in middle of average therapeutic range
Induces CYP-450, resulting in multiple interactions with other medications

Question 20

Valproate: mechanism

Answer 20

• Increased rate of GABA turnover
• Reduction of NMDA glutamate receptor-mediated excitation
• Inhibit sustained repetitive firing of neurons with blockage of voltage-dependent sodium channels

Question 21

Valproate: indications

Answer 21

Complex partial seizures, generalized, absence seizures

Also effective for headache and mood stabilization

Question 22

Valproate: dose

Answer 22

15 mg/kg a day in divided doses with weekly dose increases of 5-10 mg/kg
IV available
Long-acting form available

Question 23

Valproate: side effects

Answer 23

• Common: drowsiness, tremor, nausea, vomiting, hair loss, weigh gain, tremor
• Serious: hepatotoxicity, hemorrhagic pancreatitis

Question 24

Felbamate: mechanism

Answer 24

Interaction with NMDA receptors, resulting in decreased excitatory amino acid neurotransmission

Question 25

Felbamate: indications

Answer 25

Partial seizures with or without secondary generalization Originally developed for Lennox-Gastaut syndrome Use in severely refractory patients only

Question 26

Felbamate: dose

Answer 26

1,200 mg/day in divided doses every 8 hours | Slowly increased to target range of 2,400-3,600 mg/day

Question 27

Felbamate: side effects

Answer 27

- Common: nausea, headache, insomnia. Significant weight loss in long-term use - Serious: aplastic anemia, hepatic failure. Most serious teratogenic AED, should be avoided in all women of childbearing age. - CBC and LFT every 2 weeks for 1st 6 months

Question 28

Gabapentin: mechanism

Answer 28

- Reduction of glutamate release at cortical synapses | - Reduction of activity-dependent release via interaction with P/Q-type voltage-gated calcium channels

Question 29

Gabapentin: indications

Answer 29

Partial seizures

Question 30

Gabapentin: dose

Answer 30

300 mg/day with rapid escalation to initial target dose of 1,800 mg/day in 3 divided doses. Can be as high as 3,600 mg/day

Question 31

Gabapentin: side effects

Answer 31

- Common: somnolence, dizziness, ataxia, weight gain, and fatigue - Not metabolized in liver, few drug interactions

Question 32

Lacosamide: mechanism

Answer 32

- Modifies sodium channels | - Inactivates high-frequency neuronal firing

Question 33

Lacosamide: indication

Answer 33

Partial seizures

Question 34

Lacosamide: dose

Answer 34

100 mg in 2 divided doses. Increase to 100-40 mg/day | IV available

Question 35

Lacosamide: side effects

Answer 35

- Common: dizziness (esp in combo with other Na channel modulators), nausea, headache, diplopia - May cause PR interval prolongation - Little drug-drug interaction

Question 36

Lamotrigine: mechanism

Answer 36

Blocks excitatory sodium ion channels in a voltage-dependent and use-dependent manner

Question 37

Lamotrigine: indication

Answer 37

Partial and generalized seizures, including primary generalized seizures Mood stabilizing

Question 38

Lamotrigine dose

Answer 38

25 mg every day to be titrated up by 25 mg every 2 weeks until 100 mg/day Maintenance 200-400 mg/day If on enzyme-inducing: start at 50mg/day. Titrate up to 300-500 mg/day. If taking valproate: start 25 mg every other day, titrate up to 100-200 mg/day Long-acting form available

Question 39

Lamotrigine: side effects

Answer 39

- Common: dizziness, ataxia, somnolence, headache, blurred vision, nausea, vomiting. Insomnia - Serious: Rash with rapid escalation or valproic acid coadministration. Can be life threatening

Question 40

Levetiracetam: mechanism

Answer 40

Modifies synaptic protein SV2A

Question 41

Levetiracetam: indications

Answer 41

Partial and generalized epilepsy

Question 42

Levetiracetam: dose

Answer 42

1,000 mg/day divided in 2 doses Increase to reach target of 1,000-3,000mg/day IV form available Long-acting form available

Question 43

Levetiracetam: side effects

Answer 43

Common: somnolence, irritability, ataxia