ANTICONVULSANT AND ANTIPARKINSON DRUGS

Question 1

definition:

a family of chronic neurobiological disorders caused by development of a persistently low seizure threshold and characterized by periodic, pnpredictable seizures

Answer 1

epilepsy

Question 2

what is the prevalence of epilepsy by age 20? by age 80?

Answer 2

1% by age 20

3% by age 80

Question 3

how is epilepsy managed?

Answer 3

70% – currently available anticonvulsants

20% – surgery

10% – intractable

Question 4

define the principles of epilepsy pharmacotherapy

Answer 4

1. drug tx is symptomatic
2. most anticonvulsants have low therapeutic index
3. pharmacokinetics are important

Question 5

definition:

Na channels, Ca²⁺ channels, SV2A, GABA_A receptors, GABA transporters, GABA transaminase, K+ channel openers, and AMPA receptor antagonists

Answer 5

molecular targets of antiepileptic drugs

Question 6

what is the 1st mechanism of AED (antiepileptic drug) activation?

name two AEDs that produce this effect

Answer 6

enhance Na channel inactivation

1. carbamazepine (tegratol)
2. topiramate (topomax)

Question 7

name the AED:

P450 inducer (1/2 life shortens from 36hr to 8-12hr with chronic tx)

common adverse reactions: diplopia, ataxia, drowsiness

also used for neuropathic pain and bipolar disorder

Answer 7

carbamazepine (tegratol)

Question 8

name the AED:

D-fructose analog

multiple mechanisms of action (block Na channels, increases affinity of GABA for its receptors, blocks AMPA-type glutamate receptors)

T1/2 = 21hr; mostly excreted unchanged in the liver

broad spectrum anticonvulsant, widely used

common adverse reactions: sleepiness, dizziness, balance issues, often resolve over time

also used for migraine prophylaxis

Answer 8

topiramate (topomax)

Question 9

what is the 2nd mechanism of action of AEDs?

name the AED that produces this effect.

Answer 9

block Ca channels

ethosuximide (zarontin)

Question 10

name the AED:

drug of choice for absence epilepsy

t-type Ca channels not involved in transmitter release

no plasma protein binding

T1/2 = 40-60hr with renal excretion

Answer 10

ethosuximide (zarontin)

Question 11

what is the 3rd mechanism of action of AEDs?

name two drugs that produces this effect

Answer 11

enhance GABAergic inhibition

valproate (depakote)

tiagabine

Question 12

name the AED:

broad-spectrum anticonvulsant

divalproex Na – sustained release form

hepatotoxicity – contraindicated in hepatic disease, children < 2yo

mixed mechanism: also blocks Na channels

also used for bipolar disorder, migraine prophylaxis

Answer 12

valproate (depakote)

Question 13

AED interactions:

carbamezepine, phenytoin, phenobarbital

Answer 13

induce metabolism of other drugs

Question 14

AED interactions:

valproate, felbamate

Answer 14

inhibit metabolism of other drugs

Question 15

AED interactions:

valproate, phenytoin

Answer 15

highly protein bound

Question 16

what is the consequence of administration of carbamazepine, ethosuximide, cloazepam, lamotrigine, topiramate, or tiagabine in the presence of a mutation of the 3A4*1B P450 isoform?

Answer 16

decreased clearance, increased toxicity

Question 17

what are the factors that produce fetal anomalies in 4-6% of pregnancies by epileptic mothers? (3)

Answer 17

1. drug effects
2. consequence of the mother’s underlying diseases
3. consequence of maternal seizures

Question 18

T/F:

all anticonvulsant drugs carry some teratogenic risk

Answer 18

TRUE

Question 19

what can be taken to reduce the teratogenic risk of anticonvulsant therapy?

Answer 19

folate (≥ 1mg/day)

Question 20

definition: basal ganglia disorders

degeneration of dopaminergic neurons in substantia nigra pars compacta

Answer 20

parkinsonism

Question 21

definition: basal ganglia disorders

degeneration of cholinergic and GABAergic stratal neurons

Answer 21

Huntington’s disease

Question 22

definition: basal ganglia disorders

damage to one subthalamic nucleus (often due to vascular accident)

Answer 22

Ballism

Question 23

definition: basal ganglia disorders

iatrogenic disorder due to long term treatment with antipsychotics

Answer 23

tardive dyskinesia

Question 24

definition:

resting tremor, (cogwheel) rigidity, bradykinesia, (later) stooped posture

Answer 24

motor symptoms of parkinson’s disease

Question 25

what is the mean onset age of parkinson's disease?

Answer 25

60yr

Question 26

parkinson's disease was the first disease of the brain demonstrated to have \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Answer 26

a molecular basis

Question 27

what is the proximal cause of parkinsonism?

Answer 27

degeneration of \> 40% of the nigral dopaminergic neurons

Question 28

describe the primary therapy for parkinson's disease

Answer 28

replace the lost dopamine (L-DOPA, carbidopa)

Question 29

what are the short-term side effects of dopamine replacement therapy?

Answer 29

nausea, cardiac arrythmias

Question 30

what are the lont-term side effects of L-DOPA therapy?

Answer 30

dyskinesias, "end-of-dose" deterioration, "on-off" effect hallucinations, delirium, depression, sleep disturbances (clozapine – can blunt psychotic effects)

Question 31

describe the secondary therapy for parkinson's disease

Answer 31

directly activate dopamine receptors in striatum

Question 32

what is the prototype secondary parkinson's disease drug therapy that is a D2 agonist, has \>90% first pass metabolism and a 3hr 1/2 life?

Answer 32

bromocryptine (parlodel)

Question 33

what secondary parkinson's disease drug therapy has a 66 1/2 hour half life, and is take 2X/week PO?

Answer 33

cabergoline

Question 34

what sencondary parkinson's disease drug therapy is often used initially, or in combination with L-DOPA, causes fewer dyskinesias than L-DOPA, but may cause nausea, mental confusion, and hallucinations?

Answer 34

ropinirole

Question 35

describe the third therapy for parkinson's disease

Answer 35

scavenge free radicals & inhibit MAO-B

Question 36

what is the prototype third parkinson's disease drug therapy that is metabolized to methamphetamine (stimulates DA release), and who's interaction with tricyclic antidepressants and SSRIs leads to serotonin syndrome (hyperthermia, hypertension, rigidity)

Answer 36

selegiline (eldepryl)

Question 37

definition: caused by triplet repeat expansion (poly-Q) of huntingtin, displays autosomal dominant inheritance, results in the death of GABAergic and cholinergic striatal neurons

Answer 37

Huntington's disease

Question 38

what is the huntington's disease drug therapy approve in 2008, that is a VMAT2 inhibitor that depletes dopamine, reduces dyskinesias but not cognitive decline or mood issues

Answer 38

tetrabenazine