Anti convulsants 1.3

Question 1

Ethosuximide (Zarontin)*: Mechanism of Action:

Answer 1

• Blocks t-type Ca2+ channels of thalamic
interneurons that appears to interrupt the
neuronal hypersynchrony of thalmocortical
pathways seen in absence seizures

Question 2

Ethosuximide (Zarontin)*: Uses

Answer 2

• Absence seizures (only indication)

Question 3

Ethosuximide (Zarontin)*: Side Effects

Answer 3

• GI irritation: nausea, vomiting, anorexia
• CNS depression – drowsiness, lethargy,
euphoria, dizziness, headache, hiccough
• Rashes – urticaria, Stevens-Johnson syndrome
• Blood dyscrasia have occurred

Question 4

Lorazepam (Ativan)**:

Answer 4

Prototype of the benzodiazepines
• Other benzodiazepine drugs commonly used:
Clonazepam (Klonopin)*
• Inhibits Spread: Myoclonic, Atonic
Clorazepate (Tranxene)
• Metabolized to Diazepam; adjunctive treatment
Clonazepam and diazepam
• IV agent status epilepticus

Question 5

Mechanism of Action

Answer 5

• Action on benzodiazepine binding site of GABAA
receptor complex leading to allosteric change
promoting GABA action
• Use and voltage-dependent blockage of Na+
channels
• Blocks neuronal Ca2+ channels at sedating doses

Question 6

Side effects

Answer 6

• See anxiolytic lecture
• Important for epilepsy withdrawal seizures following
abrupt cessation of chronic therapy

Question 7

Ethotoin (Peganone)

Answer 7

• Similar to Phenytoin, with shorter t½
• Fewer side effects and not as effective, rarely used
• Can be used in both children and adults as an
adjunct therapy
Uses
• Tonic-clonic
• Partial seizures

Question 8

Mephenytoin (Mesantoin)

Answer 8

Only in refractory patients
• Decreased gingival hyperplaysia, hirsuitism
• Greater hepatotoxicity risk, blood disorders

Question 9

Felbamate (Felbatol): Mechanisms of Action

Answer 9

• Blocks glycine activation of NMDA receptors and
may thereby inhibit processes responsible for the
initiation of seizures
• Inhibits Ca2+ channels; may have some effect on Na+
channels

Question 10

Felbamate (Felbatol): Uses

Answer 10

• Limited to the treatment of Partial Seizures that are
refractory to other drugs.
• Lennox-Gastaut syndrome in children
– Multiple seizure types, particularly tonic and atonic
seizures, but also including absence seizures (“typical”
petit mal) and myoclonic seizures (“atypical” petit mal) as
well as nonconvulsive status epilepticus

Question 11

Felbamate (Felbatol): Side Effects

Answer 11

• Gastrointestinal: anorexia, vomiting, nausea
• CNS: insomnia, headache
• Allergic reactions: hematological and
dermatological reactions
• Acute liver failure
• Aplastic Anemia

Question 12

Felbamate (Felbatol): Drug Interactions

Answer 12

• May alter concentrations of other anticonvulsants

– Inhibits CYP2C19, Induces CYP3A4

Question 13

Gabapentin (Neurontin): Mechanisms of Action

Answer 13

• Unknown:
• Chemically related to GABA, but does not work through
the GABA receptor
• Increases release of GABA from central neurons
• No direct effect on GABA receptors

Question 14

Gabapentin (Neurontin): Uses

Answer 14

• Partial seizures – adjunctive to other anticonvulsants
• Adjunctive therapy for partial seizures-Pediatric patients
(3-12 y.o.)
• Postherpetic neuralgia
• Diabetic Neuropathy
• Migraine

Question 15

Gabapentin (Neurontin): Side Effects

Answer 15

• CNS: ataxia, dizziness, drowsiness, nystagmus,
tremor
• Weight gain
• Dyspepsia, constipation

Question 16

Gabapentin (Neurontin): Drug Interactions

Answer 16

• Does not alter serum concentration of other
anticonvulsants
• Bioavailability is reduced with concurrent use of
antacids

Question 17

Lamotrigine (Lamictal)**: Mechanisms of Action

Answer 17

• Inhibits voltage-sensitive Na+ channels of presynaptic
membrane, similar to phenytoin and carbamazepine
• Inhibits glutamate and aspartate release
• May inhibit Ca2+ channels

Question 18

Lamotrigine (Lamictal)**: Uses

Answer 18

• Adjunct in treatment of partial seizures
• Generalized tonic-clonic
• Atonic
• Absence seizures
• Add-on therapy for Lennox-Gastaut syndrome

Question 19

Lamotrigine (Lamictal)**: Side Effects

Answer 19

Dizziness, headache, diplopia, ataxia, somnolence
• Skin rash (10%)-severe (Stevens-Johnson) and
potentially life threatening; (Antiepileptic with highest probability of happening)
• Higher risk in children-use not indicated if less than
16 years old.