Pharm - Anticonvulsants

Question 0

Fosphenytoin

Answer 0

IV anticonvulsant for Status Epilepticus Gen. Tonic/Clonic (GTC);
Mech: phenytoin pro-drug –> favors inactive state of volt-gated Na+ channel
SE: #1 = gingival hyperplasia, Worst = agranulomatosis (rare);
also: cerebellar, vestibular, GI, & Bx disturbances
Contraind: myoclonic/abscence seizures, poly-pharm w/ hepatic competing drugs

Question 1

Phenytoin

Answer 1

oral Anti-convulsant for Generalized Tonic/Clonic (GTC);
Mech: activity-dependent volt-gated Na+ blockade
(favors inactive state, reduces post-tetanic potentiation)
SE: #1 = gingival hyperplasia, cerebellar/vestibular/GI disturbances, Bx changes, agranulomatosis (rare, severe), cut. hypersensitivity!
metabolic Competition: hepatic & plasma protein binding
Contraindications: abscence or myoclonic seizures

Question 2

Carbamazepine

Answer 2

oral anticonvulsant for gen. Ton/Clonic (GTC) or partial seizures, & CN neuralgia;
Mech: favors inact. volt-gated Na+ channels; variable absorption.
SE: drowsy, dizzy, ataxia, *aplastic anemia (lethal!), hepatic/renal damage, blurred vision, GI
Contraind: absence or myoclonic seizures.

Question 3

Lamotrigine

Answer 3

oral anticonvulsant for partial, myoclonic, or GTC seizures;
Mech: potent volt-gated Na+ & Ca2+ channel blocker
SE: aseptic meningitis, dizzy, diplopia, rash

Question 4

Oxycarbamazine

Answer 4

oral anticonvulsant for partial seizures,
Mech: favors inact. volt-gated Na+ channel (carbamazine prodrug)
SE: –

Question 5

Valproate (valproic acid)

Answer 5

oral anticonvulsant for generalized absence or GTC, myoclonic seizures, migraine, or trigem. neuralgia; 1st line Tx.
Mech: block T-type Ca2+ & favor inact. volt-gated Na+ channels.
SE: GI, possible hepatotoxicity (monitor), few CNS effects!
Contraind/DDI: liver disease, drug hypersensitivity, pregnancy (teratogen) * increases [phenobarbital]!*

Question 6

Ethosuximide

Answer 6

oral anticonvulsant for absence (#1) or myoclonic seizures;
Mech: blocks T-type Ca2+ channels
* half-life > 24 hrs!*
SE: blood dyscrasias & lupus, dizzy, GI, euphoria…
Contraind: major motor epilepsy (GTC)

Question 7

Zonisamide

Answer 7

oral anticonvulsant for generalized absence, partial, or myoclonic seizures;
Mech: blocks T-type Ca2+ channels
SE: (same as ethosuximide) skin rxns, lupus, blood dyscrasias…GI, dizzy, etc.

Question 8

Gabapentin

Answer 8

for Neuropathic pain (#1), also partial or myoclonic seizures;
Mech: Structural GABA analog, binds & blocks volt-gated Ca2+ channels, maybe Na+ channels too.
* short half-life (~6 hrs)
SE: dizzy, fatigue/sleepy (less than other anticonvulsants)

Question 9

Pregabalin

Answer 9

better for neuropathic pain than seizures, but can be for low-grade parial & secondary generalized.
Mech: GABA analog –> block volt-gated Ca2+ channels.
SE: very minor (sleepy, dizzy)

Question 10

Barbiturates (phenobarbital)

Answer 10

oral anticonvulsant (GTC) & sedative;
reduce recurrence of febrile seizures
Mech: GABAa-mimetic –> non-selective CNS depression
often effective anticonvulsant at < sedative dose; long half-life.
SE: sedation (#1), hyperactive/irritable (children), confusion (elderly)
DDI: induces hepatic metab., cross-tolerance for CNS depressants.

Question 11

Benzodiazepines (Diazepam = IM, Lorazepam = IV)

Answer 11

IM/IV anticonvulsants for Status Epilepticus (GTC);

Mech: facilitate GABA binding to GABAa R –> block Na+ channels

Question 12

Tiagabine

Answer 12

oral GABA-ergic anticonvulsant, for partial seizures.

Mech: block GABA uptake into neurons and glia

Question 13

Vigabatrin

Answer 13

oral GABA-ergic anticonvulsant for Generalized Ton/clonic epilepsy
* better as co-adjuvant for partial seizures*
Mech: irreversible inhibition of GABA transaminase –> block synthesis.
SE: drowsiness, fatigue, retinopathy

Question 14

Felbamate

Answer 14

oral anticonvulsant for GTC or partial seizures; *NOT 1st line.
Mech: glycine antagonism at NMDA Rs, may block Na+ channels, possibly neuroprotective
SE: agranulomatosis, aplastic anemia, hepatitis; insomnia, ataxia, diplopia.

Question 15

Topiramate

Answer 15

Oral anticonvulsant for partial seizures,
Mech: 1. block volt-gated Na+ channels,
2. increase efficacy of GABA at GABAa Rs,
3. block AMPA R activation

Question 16

Levitiracetam

Answer 16

oral anticonvulsant for complex partial & GTC seizures;
Mech: (unique!) unclear… binds to a synaptic vesicle protein
(does NOT act on volt-gated Na+ channels)
*prevents/relieves kindling effect!
SE: very few (psychosis = rare)