Pharmacology - Test 2 - AED Flashcards Preview

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Flashcards in Pharmacology - Test 2 - AED Deck (53):
1

Epilepsy

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

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Principles of pharmatherapy

Low therapeudic index.

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

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

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Example of AED drugs that inactivate the Na channels

carbamazepine (tegratol), phenytoin (dilantin)

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Carbamazepine action and half life

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

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Carbamazepine adverse rxns

diplopia, ataxia, drowsiness

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Carbamazepine other uses

neuropathic pain, bipolar disorder

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2nd mechanism of AED action

blocks Ca channels

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Example of Ca channel AED blocker

ethosuximide (zarontin)

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Drug of choice for absense epilepsy

ethosuximide (zarontin)

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Ethosuximide protein binding

no protein binding

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Half life of ethosuximide

40-60 hours with renal excretion

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3rd mechanism of action for AEDs

enchance GABAergic inhibition

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Drugs that enhance GABAergic inhibition

tiagabine, valproate, vigabatrin, lorazepam

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GABAergic inhibition

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.

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Valproate use

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

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Valproate contraindications

hepatic disease. children <2yr

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Valproate mechanism

GABAergic AND Na channels.

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AED p450 inducers (induces metabolism of other drugs)

carbamazepine, phentoin, phenobarbital

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AED p450 inhibitors

Valproate, felbamate

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AED highly protein bound drugs

valproate, phenytoin

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Pharmacogenetics in Anticonvulsant therapy

use P450 3A4*1B

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Defective alleles % and effect.

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

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AED and pregnancy

teratogenic risk 4-6% - Toxic metabolites.

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AED teratogenic prophylaxis

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

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2 ways to classify AEDs

By mechanism of action. By most common seizure type affected

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3 drugs with mixed mechanism of action

valproate, topiramate, zonisamide.

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SV2A target

levetiracetam

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Kv7 channel opener

aezogabine

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4 types of basal ganglia disorders

parkinsonism, huntingtons, ballism, tardive dyskinesia

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parkinsonism

degredation of dopaminergic neurons in substantia nigra pars compacta

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huntingtons disease

degeneration of cholinergic and GABAergic striatal neurons

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Ballism

damage to one subthalamic nucleus (vascular accident induced)

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tardive dyskinesia

iatrogenic disorder due to long term treatment with antipsyhotics

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Parkinsons motor symptoms

resting tremor, limb rigidity, bradykinesia, stooped posture

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Parkinsons progression

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

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Parkinsons etiology

unknown: viral infection? environmental neurotoxin?

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Parkinson's disease therapy #1

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

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carbidopa role in parkinsons therapy

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

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Sinemet

drug that packages l-dopa and carbindopa

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Short term SE of parkinsons therapy

nausea, arrhythmias.

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Long term SE of L-DOPA therapy

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)

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Parkinsons Disease Therapy #2

directly activate dopamine receptors in striatum neurons

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Prototype dopamine receptor activator drug

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

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Bromocryptine half life

3 hours.

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Cabergoline (off-label)

version of D2 agnoist with a 66 hour half life

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Ropinirole

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

48

Parkinson's therapy #3

Scavenge free radicals and inhibit MAO-B

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Selegiline

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

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Selegiline metabolization

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

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Selegiline interactions

tricyclic antidepressants and SSRI's

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Huntingtons disease

GABAergic & cholinergic striatal neurons die.

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Tetrabenazine

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