anti-epileptics Flashcards
mechanisms of anti-epileptics (5)
inactivate Na channels
inactivate Ca channels
reduce synaptic vesicle fusion
modulate glutamate receptors
modulate gaba receptors
pathophysiology of epilepsy
too much excitation or too little inhibition
are there increased or decreased levels of glutamate during seizures
increased
what is the ionotropic receptor type for GABA?
GABAA
what is the metabotropic receptor type for GABA
GABAB
targets of anti-epileptic drugs
glutamate- decrease activity at receptors
increase activity of GABA at receptors
Increase release of GABA
Inhibit breakdown of GABA
first line for treating status epilepticus
benzodiazepines: diazepam (valium), lorazepam (ativan)
first line of drug for absence seizures
ethosuximide
valproic acid
mechanism of benzodiazepines
increase affinity of GABA for the GABAA receptor
where are benzodiazepines metabolized
liver
side effects of benzodiazepines
sedative
withdrawal symptoms due to tolerance
mechanism of vigabatrin
inhibit GABA-T to reduce GABA breakdown
indication for vigabatrin (sabril)
complex partial seizures that are refractory to several others AEDs
infantile spasms
drug interaction of vigabatrin
reduces plasma concentration of primidone
side effects of vigabatrin
concentric visual field deficit (can be irreversible)
drowsiness
dizzinesss
weight gain
what is carbamazepine indicated for
focal seizures and GTCSs
mechanism of carbamazepine
block tetanic firing
increases Na channel inactivation, reduces transmitter release
potentiates GABA response
what is carbamazepine used for other than seizures
bipolar disorder
carbamazepine toxicities
ataxia, diplopia, nystagmus, dizziness
tolerance to side effects
aplastic anemia
rash- Stevens Johnson Syndrome, Toxic Epidermal Necrolysis
what drugs should never be used with carbamazepine
drugs that inhibit hepatic metabolism- increases toxicity
mechanism of phenytoin (dilantin)
blocks tetanic firing
increases Na channel inactivation
releases neurotransmitter release
indication for phenytoin
focal seizures and GTCSs
status epilepticus
notable phamacokinetic aspect of phenytoin
oral absorption peak time variable from patient to patient, difficult to get dosing within therapeutic range
functions at 1st order kinetic at low doses and zero order kinetics at high doses
side effects of phenytoin
cardiac arrhythmias
dizziness
nystagmus
headaches
rash
gingival hyperplasia and hirsutism
mechanism of primidone (mysoline)
similiar to phenytoin- increase Na channel inactivation
notable mention- phenobarbital is a metabolite (enhances GABAA receptor activity) but this is not thought to be part of the mechanism of action
what disorder is treated with primidone
focal dyscognitive seizures (not used much now in favor of carbamazepine and phenytoin)
primidone pharmacokinetics
slow, complete absorption
half life 8-12 hours
induces hepatic enzymes
primidone toxicities
drowsiness
nystagmus and ataxia only at excessive doses
in what diagnoses would you prescribe topiramate
partial seizures and GTCSs
anti-migraine/migraine prophylaxis
mechanism of action of topiramate
increase Na channel inactivation
inhibits kainate/AMPA receptors
Enhances GABA
side effects of topiramate (topamax)
somnolence
fatigue
weight loss
nervousness
congnitive impairment
indication for use of lamotrigine (lamictal)
partial seizures
GTCSs
mechanism of action of lamotrigine
increase Na channel inactivation
inhibit release of amino acids by acting on voltage gated Ca channels
(decrease Na and decrease Ca)
side effects of lamotrigine
rash- usually only in children
indication for zonisamide
broad spectrum
absence, myoclonic, infantile spasms
mechanism of zonisamide
Na channel (decrease Na)
acts on T-type voltage gated Ca channels (decrease Ca)
side effects of zonisamide
drowsiness, cognitive impairment, skin rashes
no interaction with other AEDs
indication for gabapentin
adjunct therapy: focal seizures
chronic pain management
mechanism of gabapentin
decreases Ca- binds to voltage gated Ca channels, decreases glutamate release
(does not interact with GABAA as designed)
(inhibits GABA-T but not at physiologic concentrations)
drug interaction of gabapentin
very few!
cimetidine and aluminum/magnesium antacids
which drugs are the most effective anti-epileptics (think mechanism of action)
drugs that block transmitter release
(drugs that affect Ca channels, Na channels, or vesicle fusion blocking)
indication for levetiracetam
partial seizures and GTCSs
mechanism of action of levetiracetam (keppra)
targets synaptic vesicle protein 2A (SV2A) protein ligand
inhibit calcium dependednt amino acid transmitters by interfering with vesicle fusion
side effects of levetriacetam
dizziness
somnolence
weakness
dermatologic conditions
behavioral changes in psych patients
drugs that enhance GABA transmission
vigabatrin
benzodiazepines
barbiturates
drugs that cause Na channel inactivation (6)
phenytoin
carbamazepine
lamotrigine
primidone
topiramate
zonisamide
what type of drugs should you choose for absence seizures
ones that affect Ca channels
they are associated with T-type Ca channels
Drugs that affect T-type Ca channels
valproate
ethosuximide
indication for ethosuximide
absence seizures and myoclonic seizures
mechanism of ethosuximide
inhibits T-type Ca channel activity in thalamic neurons
pharmacokinetics of ethosuximide (zarontin)
not protein bound
metabolized by microsomal enzymes
side effects of ethosuximide
gastric distress- pain, nausea, vomiting
indication of valproic acid (depakote)
absence, generalized, and complex partial seizures
mechanism of valproic acid
decrease Na and Ca
increase GABA
similar to phenytoin- blocks tetanic firing by increasing Na inactivation, reduce transmitter release
reduce T-type Ca channel activity
inhibits breakdown of GABA
pharmacokinetics of valproic acid
90% protein bound
well absorbed
half life 9-18 hours
side effects of valproic acid
nausea, vomiting, GI distress
sedation
hepatotoxicity
what should you give during pregnancy
lowest effective dose of a monotherapy
drug withdrawal dangerous for fetus
what drugs should you consider in simple/complex PARTIAL seizures?
conventional: carbamazepine or phenytoin
recently developed: gabapentin, topiramate, lamotrigine, levetiracetam
drugs to consider for generalized tonic-clonic
conventional agents: carbamzepine, phenytoin and valproic acid
recently developed: gabapentin, topiramate, lamotrigine, lacosamide
what drugs to consider for absence seizures
conventional agents- ethosuximide and valproic acid
recently developed- lamotrigine
what drugs to consider for myoclonic seizures
conventional: valproic acid or clonazepam
recently developed: levetiracetam
what drugs to consider for status epilepticus
lorazepam, diazepam, fosphenytoin, phenytoin, or phenobarbital
