Anticonvulsant and Antiparkinson Drugs

Question 1

Carbamazepine (tegratol)

Answer 1

Enhance sodium channel inactivation
Absorb into the cell and bind to sodium channels, locking them in inactivated position
Makes it difficult to send signal along the nerve
P450 inducer (half-life shortens from 36 hours to 8-12 hours with chronic use)
Causes diplopia, ataxia, drowsiness
Tegratol-XR sustained release form
Used for neuropathic pain, bipolar disorder
Targets Partial Complex seizures

Question 2

Ethosuximide (zarontin)

Answer 2

Calcium channel blocker
Drug of choice for absence epilepsy
T-type calcium channels not involved in transmitter release
No plasma protein binding
Half-life 40-60 hours with renal excretion

Question 3

Levetiracetam

Answer 3

Synaptic Vesicle Glycoprotein (SV2A) target
Targets Partial Complex seizures
Inhibits presynaptic calcium channels
Reduces neurotransmitter release
It is thought poorly functioning SV2A transporters allow calcium buildup in the synapse which can increase excitability.
Preliminary studies show poorly functioning SV2A transporters have less GABA activity.

Question 4

Valproate

Answer 4

Enhances GABAergic Inhibition
Thought to bind to GAB reuptake transporters, increasing GABA activity
Broad-spectrum anticonvulsant
Divalproex NA is sustained release form
Hepatotoxicity
Mixed mechanism: Also blocks Na channels
Also used for bipolar disorder and migraine prophylaxis
Treats generalized tonic-clonic seizures, absence seizures (if t-c also present), and myoclonic seizures

Question 5

Tiagabine

Answer 5

Enhances GABAergic Inhibition
Thought to bind to GAB reuptake transporters, increasing GABA activity
Targets Partial Complex seizures

Question 6

Drugs that induce the metabolism of other drugs

Answer 6

Carbamazepine, phenytoin, and phenobarbital

Question 7

Drugs that inhibit metabolism of other drugs

Answer 7

Valproate, felbamate

Question 8

Drugs that are highly protein bound

Answer 8

Valproate, Phenytoin

Question 9

Parkinson’s Disease Therapy 1

Answer 9

Replace lost dopamine
L-DOPA, Carbidopa
Carbidopa inhibits the peripheral metabolism of L-DOPA by L-amino acid decarboxylase, so bother given together
Cross BBB and convert to dopamine by aromatic acid decarboxylase
Causes dyskinesias, "end of dose" deterioration, and "on-off" effect
Need clozapine (D2 antagonist) to blunt hallucinations, delerium, depression, sleep disturbance.

Question 10

Parkinson’s Disease Therapy 2

Answer 10

Activate dopamine receptors in striatum
Bromocriptine (Parlodel)
>90% first pass metabolism
Half-life 3 hours
Cabergoline (off-label) has 66 hour half-life
Ropinirole causes fewer dyskinesias than L-DOPA, is often used initially or in combination with L-DOPA, and causes nausea, mental confusion, and hallucinations

Question 11

Parkinson’s Disease Therapy 3

Answer 11

Scavenge free radicals and inhibit MAO-B
Selegiline (eldepryl)
Metabolized to methamphetamine (stimulates dopamine release)
MAO-B found in 5HT but not DA neurons in substatia nigra
MAO-B responsible for the breakdown of DA
Best used along with L-DOPA or carbidopa
Interacts with tricyclic antidepressants and SSRIs to cause serotonin syndrome (hyperthermia, hypertension, rigidity)

Question 12

Huntington’s Disease

Answer 12

Caused by triplet repeat expansion of Huntingin Protein
GABAergic and cholinergic striatal neurons die
Tetrabenazine: VMAT inhibitor that depletes dopamine, reduces dyskinesias