Pharmacology - Test 2 - AED

Question 1

Epilepsy

Answer 1

Family of chronic neurologic disorders characterized by periodic or unpredicable seizures. Prevalence 3% by 80. 70% on anticonvulsants

Question 2

Principles of pharmatherapy

Answer 2

Low therapeudic index.

Question 3

1st Mechanism of AED (anti ep drug) action.

Answer 3

Enchances Na channel inactivation by acting on the inside of the channel.

Question 4

Example of AED drugs that inactivate the Na channels

Answer 4

carbamazepine (tegratol), phenytoin (dilantin)

Question 5

Carbamazepine action and half life

Answer 5

p450 inducer. 1/2 life hortens from 36hr to 8-12 hours with chronic treament. Tachyphylactic

Question 6

Carbamazepine adverse rxns

Answer 6

diplopia, ataxia, drowsiness

Question 7

Carbamazepine other uses

Answer 7

neuropathic pain, bipolar disorder

Question 8

2nd mechanism of AED action

Answer 8

blocks Ca channels

Question 9

Example of Ca channel AED blocker

Answer 9

ethosuximide (zarontin)

Question 10

Drug of choice for absense epilepsy

Answer 10

ethosuximide (zarontin)

Question 11

Ethosuximide protein binding

Answer 11

no protein binding

Question 12

Half life of ethosuximide

Answer 12

40-60 hours with renal excretion

Question 13

3rd mechanism of action for AEDs

Answer 13

enchance GABAergic inhibition

Question 14

Drugs that enhance GABAergic inhibition

Answer 14

tiagabine, valproate, vigabatrin, lorazepam

Question 15

GABAergic inhibition

Answer 15

Doesn’t inhibit GABA, means allows GABA to do exhibit its ‘inhibiting effects.’ Works on GABA transport blocker. Allows GABA concentration in synaptic cleft to be high.

Question 16

Valproate use

Answer 16

Broadly used. Also used for bipolar disorder, migraine prophylaxis.

Question 17

Valproate contraindications

Answer 17

hepatic disease. children <2yr

Question 18

Valproate mechanism

Answer 18

GABAergic AND Na channels.

Question 19

AED p450 inducers (induces metabolism of other drugs)

Answer 19

carbamazepine, phentoin, phenobarbital

Question 20

AED p450 inhibitors

Answer 20

Valproate, felbamate

Question 21

AED highly protein bound drugs

Answer 21

valproate, phenytoin

Question 22

Pharmacogenetics in Anticonvulsant therapy

Answer 22

use P450 3A4*1B

Question 23

Defective alleles % and effect.

Answer 23

African Americans 53-69%. v clearance and ^ toxicity

Question 24

AED and pregnancy

Answer 24

teratogenic risk 4-6% - Toxic metabolites.

Question 25

AED teratogenic prophylaxis

Answer 25

Folate >1mg/day to minimize risk of neural tube defects. Switch to monotherapy.

Question 26

2 ways to classify AEDs

Answer 26

By mechanism of action. By most common seizure type affected

Question 27

3 drugs with mixed mechanism of action

Answer 27

valproate, topiramate, zonisamide.

Question 28

SV2A target

Answer 28

levetiracetam

Question 29

Kv7 channel opener

Answer 29

aezogabine

Question 30

4 types of basal ganglia disorders

Answer 30

parkinsonism, huntingtons, ballism, tardive dyskinesia

Question 31

parkinsonism

Answer 31

degredation of dopaminergic neurons in substantia nigra pars compacta

Question 32

huntingtons disease

Answer 32

degeneration of cholinergic and GABAergic striatal neurons

Question 33

Ballism

Answer 33

damage to one subthalamic nucleus (vascular accident induced)

Question 34

tardive dyskinesia

Answer 34

iatrogenic disorder due to long term treatment with antipsyhotics

Question 35

Parkinsons motor symptoms

Answer 35

resting tremor, limb rigidity, bradykinesia, stooped posture

Question 36

Parkinsons progression

Answer 36

affects ~1,000,000 americans, mean age of onset 60 years.

Question 37

Parkinsons etiology

Answer 37

unknown: viral infection? environmental neurotoxin?

Question 38

Parkinson’s disease therapy #1

Answer 38

replace the lost dopamine (L-Dopa, carbidopa). Only 1-3% crosses BBB where it is converted to dopamine, packaged, and released..

Question 39

carbidopa role in parkinsons therapy

Answer 39

decarboxylase inhibitor. slows peripheral conversion of L-dopa to dopamine. doesn’t cross BBB. Improves central concentration

Question 40

Sinemet

Answer 40

drug that packages l-dopa and carbindopa

Question 41

Short term SE of parkinsons therapy

Answer 41

nausea, arrhythmias.

Question 42

Long term SE of L-DOPA therapy

Answer 42

dyskinesia
end of dose deterioration (time to take dose nears, symptoms worsen)
On-off effect (unknown why: randomly effective/ineffective)
hallucinations *
delerium *
depression *
sleep disturbances *
* = treatment by clozapine (d2 antagonist)

Question 43

Parkinsons Disease Therapy #2

Answer 43

directly activate dopamine receptors in striatum neurons

Question 44

Prototype dopamine receptor activator drug

Answer 44

bromocryptine, d2 agonist. >90% 1st pass metabolism

Question 45

Bromocryptine half life

Answer 45

3 hours.

Question 46

Cabergoline (off-label)

Answer 46

version of D2 agnoist with a 66 hour half life

Question 47

Ropinirole

Answer 47

Parkinsons drug. d2 agonist, causes fewer dyskinesias than L-DOPA. Can be used in combination of L-DOPA

Question 48

Parkinson’s therapy #3

Answer 48

Scavenge free radicals and inhibit MAO-B

Question 49

Selegiline

Answer 49

Parkinsons Drug. MAO-B inhibitor. increases amount of dopamine available in nerve terminals.

Question 50

Selegiline metabolization

Answer 50

metabolized to methamphetamine in the brain, which stimulates DA release.

Question 51

Selegiline interactions

Answer 51

tricyclic antidepressants and SSRI’s

Question 52

Huntingtons disease

Answer 52

GABAergic & cholinergic striatal neurons die.

Question 53

Tetrabenazine

Answer 53

Huntingtons Drug - VMAT2 inhibitor that depletes dopamine, reduces dyskinesia. Not a cure.