Anti-Epileptics Flashcards
Screening test for Absence seizure drugs
Pentylenetetrazol
Screening test for GTCS and complex partial seizure drugs
Maximal Electroshock Test
MOA of drugs identified by Maximal Electroshock Test
prolonged inactivation of VG Na channels
Drugs that inhibit presynaptic glutamate VG Na channels
Lancosamide
Lamotrigine
Carbamezapine
Phenytoin
Drugs that inhibit presynaptic glutamate VG Ca channels
Ethosuximide
Lamotrigine
Pregabalin
Gabapentin
Drugs that inhibit presynaptic glutamate K channels
Retigabine
Drugs that inhibit glutamate SV2A (synaptic vesicle protein)
Levetiracetam
Drugs that inhibit presynaptic glutamate CRMP-2
Lacosamide
Drugs that inhibit postsynaptic glutamate AMPA receptors
Phenobarbital
Topiramate
Lamotrigine
Drugs that inhibit postsynaptic glutamate NMDA receptors
Felbamate
Drug that inhibits GAT-1
Tiagabine
Drug that inhibits GABA-T
Vigabatrin
Drugs that act on GABAa receptors
Benzo & Phenobarbital
MOA of tiagabine
Inhibits GABA reuptake by blocking GAT-1
MOA of vigabatrin
Prolongs GABA half life by blocking degradation via GABA-T
Hallmark of simple partial seizure
presevation of consciousness
Usual location of complex partial seizure
bilateral limbic system
Hallmark of complex partial seizure
automatism
Feature of secondarily generalized seizure
Amnestic
Length of tonic phase of GTCS
15-30sec
length of clonic phase of GTCS
60-120 sec
Seizure type with sudden onset and abrupt cessation
Petit mal (absence)
Duration of Absence seizures
10-45 sec
Age of onset of absence
childhood or adolesence
EEG findings of absence
2.5-3.5Hz spike and wave pattern
Presentation of atonic seizure
sudden loss of postural tone
Basis of epileptic treatment
empiric seizure classification
When is multipple drug therapy needed?
when two or more types of seizure occur in the same patient
How to discontinue anti-epileptics
reduce dose gradually
Most common cause of failure of therapy
faulty compliance
N substitution of heterocyclic ring
hydantoin
CN substitution of heterocyclic ring
Barbiturates
O substitution of heterocyclic ring
Oxazolidinedione
C substitution of heterocyclic ring
Succinamides
NH2 substitution of heterocyclic ring
Acetylureas
Conventional drugs used for all partial seizures and GTCS
Carbamenzapine, Phenytoin, Valproate
Conventional drugs for Absence
Ethosuxamide, Valproate
Conventional drug for myoclonic seizure
Valproate
Structure of phenytoin
diphenolhydantoin
2 phenols + hydantoin (N)
Substitution responsible for sedation
alkyl
Major MOA of phenytoin
block presynaptic VG Na channels in inactive state
reason for use dependent effect of phenytoin
preferential binding to and prolongation of inactivated state of VG Na channel
Presynaptic effects of phenytoin
decrease glutamate release
inscrease GABA release
Amount of absorption of phenytoin salt in GI tract
almost complete
Therapeutic levels of Phenytoin
10-20 mcg/mL
Oral therapy dose for adults (Phenytoin)
start at 300mg/day
Relationship between phenytoin dose and plasma concentrations
Non-linear (metabolism is saturable)
Why is Phenytoin not recommended to be given IM
drug precipitation in muscle occurs & unpredictable absorption
Drug interaction of Pheytoin
Enzyme INDUCER
Most common ADR of Phenytoin
diplopia and ataxia
gingival hyperplasia and hirsutism (less common)
ADRs of long term use of phenytoin
Coarsening of facial features, mild peripheral neuropahty, osteomalacia
Prodrug of Phenytoin
Fosphenytoin
Advantage of Fos phenytoin over phenytoin
more soluble
Fosphenytoin IV indication
convulsive status epilepticus
DOC for convulsive status epilepticus
Fosphenytoin IV
Sites of accumulation of Fosphenytoin
brain, liver, muscle, and fat
CSF concentration of Fosphenytoin
CSF concentration proportionate to free plasma level
After therapeutic level of drug is attained, how will small rises in drug level affect patient’s physiologic response?
toxicity symptoms due to saturation of metabolism
Toxicity of rapid IV push Fosphenytoin
cardiac arrhythmias
Moeity in carbamazepine structure
ureide
Indications of Carbamazepine
Trigeminal neuralgia
Neuropathic pain
Manic-depressive pX
Anti-epileptic drug used for trigeminal neuralgia
Carbamanzepine
AED drug similar to imipramine and other anti-depressants
Carbamazepine
MOA of carbamazepine
block presynaptic VG Na channels in inactive state
Is carbamazepine sedating?
No carbamazepine is not sedating
Drug interaction of Carbamanzepine
Enzyme INDUCER
can increase metabolism of Primidone, Phenytoin, Ethosuximide, Valproic Acid, Clonazepam
Active metabolite of carbamanzepine
Carbamazepine-10,11-epoxide
Therapeutic level where you may experience diplopia with carbamazepine
7mcg/mL
Drug interaction of Valproic Acid
Enzyme Inhibitor
Drug interaction of Phenobarbital
Enzyme INDUCER
Most common dose-related ADR of Carbamazepine
Diplopia and ataxia
Most common idosyncratic ADR of carbamazepine
erythematous skin rash
Most fatal idosyncratic ADRs of carbamazepine
blood dyscrasias, aplastic anemia, agranulocytosis within 4 months of treatment
Recommended action for carbamazepine toxicity
careful monitoring rather than discontinuation (unless persistent)
Benefit of Oxcarbazepine over carbamazepine
improved toxicity profile