Antiepileptic pharmacotherapy Flashcards
MOA of Na+ blocking antiepileptics
Binds to inactive form of Na+ channels, resulting in preferential inhibition of epileptic focus
MOA of Ca++ blocking antiepileptics
Thanlmic T-type Ca++ channels inhibit absence seizures
Presynaptic HVA Ca++ channels- suppresses Glu signalling
Ways of enhancing GABA signalling
Activate GABA-A receptors
inhibit GABA re-uptake GAT-1
Inhibit GABA degredation GABA-T
Ways of antagonizing glutamanergic transmission
antagonize receptors
block glu release SV2A
MOA of Ca++ blocking antiepileptics
Thanlmic T-type Ca++ channels inhibit absence seizures
Presynaptic HVA Ca++ channels- suppresses EAA release
Ways of antagonizing glutamanergic transmission
antagonize receptors
block glu release SV2A
Phenytoin MOA
blocks Na+ channels
Pharmacokinetics of phenytoin
oral, IV (fosphenytoin)
non-linear elimination- need to monitor in blood
plasma protein binding
hepatic CYP metabolism
Therapeutic use of phenytoin
focal and tonic-clonic seizures, SE
not effective against absence seizures
Drug interactions with phenytoin
OCPs, warfarin
Adverse effects of phenytoin
CNS- nystagmus, ataxia, and sedation Rash and SJS hirsutism blood dyscrasias teratogenic gingival hyperplasia
MOA of carbamazepine
Na+ channel blockade
carbamazepine pharmacokinetics
linear kinetics
autoinduction of CYP3A4
Therapeutic use of carbamazepine
generalized tonic-clonic seizures, simple and complex partial seizures
trigeminal neuralgia
bipolar disorder
Adverse effects of carbamazepine
CNS- drowsiness, ataxia, vertigo, diplopia, blurred vision; nausea
hyponatremia
Boxed warning- rash and SJS, asian variant more susceptible
teratogenic
Valproic acid MOA
blocks Na+ channels
Blocks T-type Ca++ channels
Stimulates GABA synthesis and inhibits degredation
Therapeutic use of valproic acid
broad spectrum anti-seizure
absence, focal and tonic-clonic seizures
bipolar disorder and migraine prophylaxis
What is divalproex
1:1 acid/salt
Adverse effects of valproic acid
GI
CNS
hepatic toxicity and pancreatitis (boxed warning)
Teratogenic (boxed warning)
Drug interaction of valproic acid
phenytoin
MOA of ethosuximide
Blocks t-type Ca++ channels in thalmic nucleus
Thalmic 3-Hz spike and wave rythms are characteristic of absence seizures
Therapeutic use of ethosuximide
drug of choice for uncomplicated absence seizures
not effective for other types
Adverse effects of ethosuximide
well-tolerated
GI
Rare SLE, leucopenia, aplastic anemia and SJS
MOA of Gabapentin
blocks HVA Ca++ channels, may reduce glu release
Pharmacokinetics of gabapentin
not metabolized; excreted unchanged in urine
Therapeutic use of gabapentin
add-on for focal and generalized seizures
posttherpetic neuralgia
off-label pain, migrane, bipolar
Adverse effects of gabapentin
some sedation and dizziness but mostly well tolerated
Lamotrigine MOA
complex, major is blockade of Na+ channels
Pharmacokinetics of lamotrigine
metabolized by glucuronidation, hepatic clearance is increased by enzyme inducers
therapeutic use of lamotrigine
Lennox-Gastaut syndrome
monotherapy for partial and secondarily generalized tonic-clonic, alternative to ethosuximide for absence
biopolar
Adverse effects of lamotrigine
dizziness, ataxia, blurred vision, nausea, vomiting
Rash/SJS boxed warning
teratogen
Levetiracetam MOA
unknown, binds to SV2A
Pharmacokinetics of levetiracetam
mostly devoid of drug interactions
Therapeutic use of levetiracetam
add on for partial or generalized tonic-clonic and myoclonic seizures
Adverse effects of levetiracetam
fatigue, dizziness, hypertension
behavioral symptoms
MOA of tiagabine
prolongs inhibitory effect of gaba by blocking GAT-1
Therapeutic use of tigabine
add on for refractory partial seizures without generalization
off-label discouraged-may promote seizures
Topiramate MOA
blocks Na+ channels, hyperpolarization, Carbonic anydrase inhibitor
Pharmacokinetics of topiramate
excreted unchanged in urine
Therapeutic use of topiramate
monotherapy for partial and generalized tonic-clonic seizures, adjunct for lennox-gastaut syndrome
migrane prophylaxis
Adverse effects of topiramate
well-tolerated
renal calculi from CA inhibition
cognitive impairment
MOA of vigabatrin
irriversible inhibitor of GABA transaminase
Therapeutic use of vigabatrin
restricted use for refractory complex partial seizures
monotherapy for infantile spasms
Adverse effects of vigabatrin
boxed warning for progressive and permanent bilateral vision loss