Neuroanatomy-Anticonvulsants

Question 1

Anticonvulsant action

Answer 1

Elevate threshold for discharge of epileptic neurons

Prevent spread

Question 2

PHENYTOIN

Answer 2

• Works on Sodium voltage gated channel.
• Drug binds when the sodium channel is in the inactivated state. So, it slows the firing rate. Normal activity is uneffected.
• Wide variation among patients in rates of absorption and metabolism; must adjust dose on individual level
• NOT given intramuscularly. because it precipitates and remains at site
• Protein binding is important; 70-95% bound; probability of toxicity increased when albumin is low, thereby increasing free concentration
• Mixed-order kinetics of metabolism: potential for rapid accumulation and toxicity with small increases in dose

Side Effects:
CNS: almost everything
Rashes, Gingival Hyperplasia, Hirsutism (excessive growth of body hair), GI, Blood Disorders, Fetal Hydantoin Syndrome, Hypoprothrombinemia in newborn, Tons of drug interactions.

Uses:
1) Generalized tonic-clonic (grand mal) - adults and older children
2) Simple partial seizures - adults and older children
3) Complex partial seizures (psychomotor)
4) Status epilepticus
not for absence seizures (totally ineffective for these)

Fosphenytoin = water soluble form. Can take orrally. Takes longer to take effect.

Question 3

CARBAMAZEPINE (Tegretol)

Answer 3

Action same as PHENYTOIN
Uses:
1) Generalized tonic-clonic
2) Simple partial (DRUG OF CHOICE)
3) Complex partial (DRUG OF CHOICE)
NOT used for Status Elipticus

Lamotrigine: Like Carbamizapine

Question 4

PHENOBARBITAL

Answer 4

Different mechanism of action of the PHENYTOINs. Reasons for this one to be used:
GABA receptor is a major hyperpolarizes neuron. Barbituates: increases the amount of time channel is onen. Basically the same thing as general anesthesia.
1.) Has a long Half-life (2-6 days in adults (steady state in weeks)), so it can be once daily dosing.
2.) Has about half of the efficacy of the other barbitals which is good because the others cause more sedation due to increased efficacy.

• 40-60% protein bound.

Toxicity:

• Drowsiness in adults; interference with cognitive function;
• paradoxical excitement in children (may require stopping drug)
• Skin rash which may rarely become severe
• Nystagmus, ataxia at excessive doses

Drug Interactions:

• ability to induce liver microsomal enzymes (increases metabolism of oral anticoagulants and clonazepam)
• valproic acid can inhibit phenobarbital metabolism.

Uses:

1) Generalized tonic-clonic and simple partial (infants and preschool)
2) Complex partial
3) Status epilepticus

Question 5

ETHOSUXIMIDE(eth-oh-sux-ih-mide) (Zarontin)

Answer 5

Ethosuximide is A drug of choice for uncomplicated absence (petit mal) seizures; and is ineffective in all others

Mechanism of action:
- Similar to PHENYTOIN just different channel. Absence seizures are caused by 3 Hz spike wave. These are caused by T type calcium channels. Ethosuzimide binds to the inactive Ca channel, and suppresses 3 Hz spike wave.

Question 6

VALPROIC ACID (Depakene, Depakote)

Answer 6

Mechanism of Action:

• Binds to inactivated state of Na channel.
• Also binds to T type Ca channel.
• Third mechanism, also inhibits enzyme that breaks down GABA.
• So, this will lead to more GABA and more hyperpolarization.

Uses:

1) Absence
2) Generalized tonic-clonic
3) Myoclonic and atonic (may be effective when other agents fail)
4) Mixed
5) Partial seizures

Gabapentin: effects amount of GABA in system. Acts more like Valproic Acid. Not quite that broad of action.

Question 7

DIAZEPAM (Valium)

Answer 7

A BENZODIAZEPINE. 
Intravenous diazepam (or lorazopam) is frequently used to terminate STATUS EPILEPTICUS 

Increase frequency of Cl channel being open. Also, sedative.

Question 8

Felbamate

Answer 8

Some indications that works on NMDA (glutamate) receptors as well as Na channels. This is basically the only one on the Glutamate receptors. Might just be on the Na channels.