1. Inherited Seizure disorders
2. Syndromes w/other neuro problems
3. Certain types of focal seizures

• Animal model used to quantify effectiveness of an anti-epileptic by inducing seizures with electric shock
• Best predictor of a drug's efficacy against: tonic-clonic & partial seizures

• Convulsant drug used in animals to test efficacy of an anti-epileptic
• Best predictor for drugs to treat absence seizures (drugs that prevent seizure with this drug prevent absence seizures best)

1. What drugs inhibit Na⁺ channels?
2. What are these good for

1. Phenytoin - esp. in hyperexcitable neurons, carbamazepine, lamotrigine, felbamate (+NMDA block), valproic acid, topiramate, barbituates (at high [])
2. Simple and complex partial seizures, generalized tonic-clonica seizures

1. What is the mechanism for absence seizures?
2. What drugs can treat?

1. Abnormal firing of T-type Ca⁺⁺ channels in patheways between thalamus and cortex
2. Ethosuximide (selective to this Ca channel - can only treat absence), valproic acid (diverse effects)

1. Benzos
2. Barbiturates
3. Topiramate - GABA_A receptors, but different binding site from benzos
4. Gabapentin - unknown mech. - slight anti-epileptic, better against pain

1. IV Barbiturates
2. IV Benzos
3. IV Phenytoin
4. IV Valproic acid

Phenytoin

M

P

T

M: Blocks Sodium channels

P: Zero order, induces P450, increased metabolism w/carbamazepine, decreased metabolism w/fluoxetine, valproic acid

T: Ataxia, nystagmus, drowsiness, rash, gingival hyperplasia, endocrine disturbances (hirsutism, DI, hyperglycemia, osteomalcia)

ALSO: Hepatitis, hematotoxicity

Carbamazepine

M

P

T

M: Block sodium channel

P: Induces P450, metabolism inhibited by fluoxetine, valproic acid

T: Nausea, ataxia, rash, nystagmus, drowsiness

ALSO: hepatitis, aplastic anemia (1:200,000)

Valproic Acid

M

P

T

M: Na channels, T-type Ca channels

P: Inhibits metabolism of phenobarbital, lamotrigine, carbamazepine

T: Nausea, drowsiness, GI upset, alopecia, asymptomatic elevation of hepatic enzymes, neural tube defects

ALSO: fulminant hepatitis (1:50,000, esp. in peds), pancreatitis

Ethosuximide

M

P

T

M: Inhibit T-type Ca channels in thalamus

P: No interactions

T: Nausea, anorexia, drowsiness, rash

ALSO: hematotoxicity

Drowsiness, ataxia, hyperactivity in kids, rash, respiratory depression

ALSO: hematotoxicity

Gabapentin

M

P

T

M: Promote GABA release by unknown mech

P: no interactions

T: Drowsiness, ataxia, fatigue, dizziness, GI upset

Lamotrigine

M

P

T

M: Block Na channels, reduced release of glutamate

P: Valproic acid inhibits its metabolism, metabolism increased by phenobarbital, phenytoin, carbamazepine

T: Rash, dizziness, tremor, ataxia, diplopia, headache, GI upset

ALSO: Stevens Johnson - rare skin condition

Levetiracetam

M

P

T

M: Interaction w/synaptic vesicle protein SV2A?

P: no drug interactions

T: Drowsiness, weakness, dizziness, behavioral problems - anxiety, apathy, depression

Felbamate

M

P

T

M: inhibit Na channels, NMDA receptors

P:?

T: Irritability, insomnia, anorexia, nausea, headache

ALSO - aplastic anemia (1:5,000), hepatic failure

Valproic acid

Clonazepam

lamotrigine

What drugs treat:

1. Primarily generalized tonic-clonic
2. Partial - all types

1. Valproic Acid, Lamotrigine, (phenytoin, barbamazepine, felbamate, phenobarbital)
2. Carbamazepine, phenytoin, lamotrigine, valproic acid (levetiracetam, gabapentin, pregabalin, phenobarbital)