Flashcards in Pharmacology - Test 2 - AED Deck (53):
Family of chronic neurologic disorders characterized by periodic or unpredicable seizures. Prevalence 3% by 80. 70% on anticonvulsants
Principles of pharmatherapy
Low therapeudic index.
1st Mechanism of AED (anti ep drug) action.
Enchances Na channel inactivation by acting on the inside of the channel.
Example of AED drugs that inactivate the Na channels
carbamazepine (tegratol), phenytoin (dilantin)
Carbamazepine action and half life
p450 inducer. 1/2 life hortens from 36hr to 8-12 hours with chronic treament. Tachyphylactic
Carbamazepine adverse rxns
diplopia, ataxia, drowsiness
Carbamazepine other uses
neuropathic pain, bipolar disorder
2nd mechanism of AED action
blocks Ca channels
Example of Ca channel AED blocker
Drug of choice for absense epilepsy
Ethosuximide protein binding
no protein binding
Half life of ethosuximide
40-60 hours with renal excretion
3rd mechanism of action for AEDs
enchance GABAergic inhibition
Drugs that enhance GABAergic inhibition
tiagabine, valproate, vigabatrin, lorazepam
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.
Broadly used. Also used for bipolar disorder, migraine prophylaxis.
hepatic disease. children <2yr
GABAergic AND Na channels.
AED p450 inducers (induces metabolism of other drugs)
carbamazepine, phentoin, phenobarbital
AED p450 inhibitors
AED highly protein bound drugs
Pharmacogenetics in Anticonvulsant therapy
use P450 3A4*1B
Defective alleles % and effect.
African Americans 53-69%. v clearance and ^ toxicity
AED and pregnancy
teratogenic risk 4-6% - Toxic metabolites.
AED teratogenic prophylaxis
Folate >1mg/day to minimize risk of neural tube defects. Switch to monotherapy.
2 ways to classify AEDs
By mechanism of action. By most common seizure type affected
3 drugs with mixed mechanism of action
valproate, topiramate, zonisamide.
Kv7 channel opener
4 types of basal ganglia disorders
parkinsonism, huntingtons, ballism, tardive dyskinesia
degredation of dopaminergic neurons in substantia nigra pars compacta
degeneration of cholinergic and GABAergic striatal neurons
damage to one subthalamic nucleus (vascular accident induced)
iatrogenic disorder due to long term treatment with antipsyhotics
Parkinsons motor symptoms
resting tremor, limb rigidity, bradykinesia, stooped posture
affects ~1,000,000 americans, mean age of onset 60 years.
unknown: viral infection? environmental neurotoxin?
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..
carbidopa role in parkinsons therapy
decarboxylase inhibitor. slows peripheral conversion of L-dopa to dopamine. doesn't cross BBB. Improves central concentration
drug that packages l-dopa and carbindopa
Short term SE of parkinsons therapy
Long term SE of L-DOPA therapy
end of dose deterioration (time to take dose nears, symptoms worsen)
On-off effect (unknown why: randomly effective/ineffective)
sleep disturbances *
* = treatment by clozapine (d2 antagonist)
Parkinsons Disease Therapy #2
directly activate dopamine receptors in striatum neurons
Prototype dopamine receptor activator drug
bromocryptine, d2 agonist. >90% 1st pass metabolism
Bromocryptine half life
version of D2 agnoist with a 66 hour half life
Parkinsons drug. d2 agonist, causes fewer dyskinesias than L-DOPA. Can be used in combination of L-DOPA
Parkinson's therapy #3
Scavenge free radicals and inhibit MAO-B
Parkinsons Drug. MAO-B inhibitor. increases amount of dopamine available in nerve terminals.
metabolized to methamphetamine in the brain, which stimulates DA release.
tricyclic antidepressants and SSRI's
GABAergic & cholinergic striatal neurons die.