Drugs for Epilepsy III PDF

PCOL 825B Drugs for Epilepsy III Alison K. Veltri, PhD 1 Contents Phenobarbital Primidone Pregabalin Tiagabine Topiramate Valproic acid Vigabatrin Zonisamide CBD Women’s health and epilepsy 2 Phenobarbital (Luminal) MOA: enhanced GABA action as inhibitory NT Indications: partial seizures, tonic-clon...

PCOL 825B Drugs for Epilepsy III Alison K. Veltri, PhD 1 Contents Phenobarbital Primidone Pregabalin Tiagabine Topiramate Valproic acid Vigabatrin Zonisamide CBD Women’s health and epilepsy 2 Phenobarbital (Luminal) MOA: enhanced GABA action as inhibitory NT Indications: partial seizures, tonic-clonic seizures, febrile seizures, primary treatment for status epilepticus Adverse effects: drowsiness (adults), hyperactivity (kids), osteoporosis, impotence, muscle aches and pains Caution: other seizure types can be provoked/worsened (especially with sudden withdrawal), autoinduction, other induction 3 Primidone (Mysoline) MOA: converted to phenobarbital Indications: same as phenobarbital Same adverse effect profile and PK as phenobarbital 4 Pregabalin (Lyrica) MOA: inhibits excitatory NT release through voltage-gated calcium channel binding Indications: adjunctive therapy for partial seizures Note: 90% drug renal excretion Common adverse effects include weight gain and edema 5 Tiagabine (Gabitril) MOA: inhibits GABA reuptake transporters Prolongs inhibitory action of synaptically released GABA Indications: partial seizures Caution: can cause seizures in individuals without epilepsy Adverse effects: dizziness, nervousness, concentration difficulty, depression, tremor PK notes: not highly protein bound; does not inhibit or induce hepatic enzymes 6 Topiramate (Topamax) MOA: blocks voltage-dependent sodium channels, potentiates inhibitory effects of GABA, acts at glutamate NMDA sites, carbonic anhydrase inhibitor Indications: partial seizures, first-line for tonic-clonic seizures Note: inhibits CYP2C19 and is induced by phenytoin, carbamazepine Adverse effects: weight loss, somnolence, paresthesias, birth defects? 7 Valproic Acid (Depakene, Divalproex/Depakote) MOA: broad spectrum anticonvulsant; sodium channel blockade, GABA transaminase blockage, T-type calcium channel action Indications: partial seizures, tonic-clonic seizures, absence seizures First-line all above Valproic acid converted to valproate in GI Multiple forms available (medication error high) Valproic acid (free acid form, same as Depakene), divalproex sodium (sodium valproate + valproic acid), Depakote (divalproex sodium) 8 Valproic Acid (Depakene, Divalproex/Depakote) PK Valproate inhibits CYP2C9, UGT, epoxide hydrolase systems Inhibits own metabolism Inhibits metabolism of phenobarbital, phenytoin, carbamazepine, ethosuximide, lamotrigine ~90% plasma protein bound 9 Valproic Acid (Depakene, Divalproex/Depakote) Adverse Effects Teratogenicity GI distress Tremors Weight gain Hair loss Hepatotoxicity (rare, but fatal) 10 Vigabatrin (Sabril) MOA: irreversible GABA transaminase inhibitor Indication: adjunctive therapy for partial seizures Caution: associated with vision loss in ~30% patients Adverse effects: weight gain, mood changes 11 Zonisamide (Zonegran) MOA: blockade of voltage-sensitive sodium channels Indications: partial seizures, tonic-clonic seizures Adverse effects: sulfonamide hypersensitivity (watch for DDI), kidney stones, oligohidrosis 12 Cannabidiol (Epidiolex) MOA: binds cannabinoid receptors in brain Indications: other seizure types Adverse effects: somnolence, sedation, can cause transaminase elevation 13 Epilepsy and Women’s Health DDIs decrease in efficacy of hormonal contraceptives Phenytoin, phenobarbital, carbamazepine, topiramate oxacarbazepine Initiate high dose folic acid with antiepileptic drugs Avoid divalproex Seizure frequency and severity can change during pregnancy PK can change during pregnancy Women who are pregnant and taking antiepileptic medications should register with North American AED Registry 14 Summary: Tonic-Clonic First-Line Lamotrigine Topiramate Valproic acid 15 Summary: Partial First-Line Carbamazepine Oxacarbazepine Phenytoin Valproic acid 16 Summary: Absence First-Line Ethosuximide Valproic acid 17 Practice 18 Thank You 19