Sz Pharmacology, Unit IV

Question 1

Phenytoin

Answer 1

VSSC inhibitor
Similar to carbamazepine
-Absorption depends on formulation– food enhances and reduces GI upset
-Extended release versions do exist
-P450 Inducer, zero-order kinetics
-Nystagmus and ataxia, with sedation in high doses
-Rash, gingival hyperplasia
-No longer first line– bad side effects, lots of DDIs
-Still effective for partial sz, generalized tonic-clonic

Question 2

Carbamazapine

Answer 2

VSSC inhibitor

• P450 inducer
• Causes diplopia and ataxia, naus/vom, drowsiness, hyponatremia
• SJS
• Rare– blood dyscrasias (aplastic anemia), hepatotoxicity
• Preferred drug in partial sz, often tried in tonic clonic

Question 3

Levetiracetam

Answer 3

• Mechanism unknown– binds SV2A (vesicle protein), but uncertain function limits insight into effect
• Ineffective against sz produced by MES or PTZ models
• Rapid absorption, available oral and IV– no P450 metabolism, minimal drug interactions
• Adverse effects– fatigue, somnelence, dizziness
• Clinical uses- 1st line in treating tonic-clonic sz

Question 4

Ethosuximide

Answer 4

• Mechanism unknown– inhibition of T-type Calcium current suspected
• Suppresses brain activity, associated with lapses in consciousness
• Metabolized by CYP3A4 and DDIs very possible
• Adverse effects– dose-related effect is gastric distress
• Less common– headache, dizz
• Drug of choice in petit mal

Question 5

Valproate/ Divalproex

Answer 5

• Mechanism unknown– probably potentiates GABA, limits T-type Ca2+ channels
• Enteric coated needed– can inhibit own metabolism, or metabolism of phenytoin, carbamazepine, ethosuximide, phenobarbitol
• GI compaints biggest deal
• Hepatotoxicity can occur
• Contraindicated in pregnancy
• DDIs– Additive with CNS depressants
• DDIS– with above lister drugs
• -DDIs– With aspirin, potentiates platelet non-adhesion
• First line in Tonic-Clonic, and good in absence sz but hepatotoxic

Question 6

Benzodiazapines

Answer 6

Enhance GABA current

• Diazapam– drug of choice in status epilepticus
• Used as adjunctive therapy in atonic and absence sz
• Tolerance problem

Question 7

Phenobarbitol

Answer 7

Enhances GABA inhibition, antagonizes clutamate

• Classic CYP450 inducer, self induces and bad DDIs
• Sedative effects and interferes with learning
• Clinical uses- excessive sedation limits use to adjunctive
• Useful in partial sz, generalized tonic-clonic
• Used in neonatal status epilepticus