anticonvulsant drugs Flashcards
epilepsy
occurrence of at least 2 unprovoked seizures separated by 24 hours
partial/focal seizures
localized onset, ascertained either by observation or EEG 3 subcategories: -simple partial -complex partial -secondarily generalized seizure
simple partial seizure
minimal spread of abnormal discharge
normal consciousness
perserved awareness
complex partial seizure
localized onset, but discharge becomes widespread, almost always involves limbic system
pt may have automatisims, memory loss, aberrant behavior
secondarily generalized seizure
partial seizure immediately precedes a generalized tonic-clonic seizure
generalized seizures
those w/o evidence of localized onset clinical manifestation indicate involvement of both brain hemispheres 4 subcategories: -generalized tonic-clonic/grand mal -absence/ petit mal -myoclonic jerking -atonic
generalized tonic-clonic/grand mal
sudden sharp tonic contraction followed by rigidity and clonic mvmts
pt may cry/moan, lose sphincter control, bite tongue, cyanotic
after seizure pt may have altered consciousness, drowsiness, or confusion
absence/petit mal
sudden onset and abrupt cessation, altered consciousness, blank stare
young kids-adolescence
myoclonic jerking
brief, shock-like mm contraction’
occur in wide variety of seizures
atonic seizures
sudden loss of postural tone, head drop, fall to floor, slumping
many pts wear helmet
generalization of Rx seizure Tx
suppress do not cure
should try different monotherapies before combining drugs
compliance is VERY important
generics may not be a good idea
MOA of AEDs in general
- affect ion Ch kinetics (delay NaCh recovery)
- augmenting inhibitory neurotransmission
- modulating excitatory neurotransmission
PK of AEDs in general
cleared chiefly by hepatic metabolism
many are potent CYP inducers
general ADRs of AEDs
common neurotoxic effects- sedation, dizziness, blurred or double vision, difficulty concentrating, and ataxia
phenytoin MOA
- blocks sustained high frequency firing of APs d/t preferential binding and prolongation of inactivated NaCh
- decrease synaptic release of glutamate and enhances release of GABA
phenytoin PK
cannot be given IM- fosphenytoin can be injected highly protein bound elimination dose-dependent CYP meta narrow therapeutic index
phenytoin uses
partial seizures
generalized tonic-clonic seizures
phenytoin ADRs
gingival hyperplasia, hirsutism
in early use can present w/rash, fever, hepatits, and lymphadenopathy,
rarely causes dermatits and stevents-johnson syndrome
phenytoin long term ADRs
worsening facial features
mild peripheral neuropathy
vit D meta abnormalities -> osteomalacia
phenytoin cardiac ADRs
hypotension, bradycardia, cardiac arrythmia, CV collapse, venous irritation, pin, thrombophlebitis
Phenytoin DDIs
related to protein binding- sulfonamides
related to meta- warfarin (increased INR), OBC (increased risk of prego)
carbamazepine and oxcarbazepine MOA
NaCh -> inhibit high frequency repetitive firing
also acts presynaptically to decrease release of glutamate
carbamazepine and oxcarbazepine PK
hepatic meta
potent CYP inducer (including its own meta)
carbamazepine and oxcarbazepine uses
partial seizures, generalized tonic-clonic seizures, trigeminal neuralgia, mania in bipolar disorder
carbamazepine and oxcarbazepine ADRs
hyponatremia and water intoxication blood dyscrasias (fatal aplastic anemia and agranulocytosis, leukopenia)- monitor mild rash to stevens-johnson syndrome
carbamazepine and oxcarbazepine DDIs
increases meta of primidone, phenytoin, OBC, valpronic acid
valpronic acid may decrease clearance
gabapentin and pregabalin MOA
analogs of GABA, but do not act directly on GABAR
bind N-type CaCh -> decrease Ca entry -> decrease release of glutamate
gabapentin uses
partial seizures
generalized tonic-clonic seizures
neuropathic pain
post-herpetic neuralgia
gabapentin and pregabalin ADRs
HA, tremor
pregabalin- controlled substance b/c may induce euphoria
lamotrugine MOA
suppresses sustained rapid firing of neurons and produces volatage and use-dependent inactivation of NaChs
inhibits V-CaChS
lamotrugine uses
adjunct when >2yrs old for partial seizures and generalized seizures
monotherapy in adults for partial seizures, adjucnt for primary genrealized tonic-clonic
also used for bipolar disorder
lamotrugine ADRs
nausea
somnolence
rash
rare stevens-johnson syndrome
lamotrugine DDIs
may increase concentration with concurrent use of OBC as well as decrease OBC efficacy
levetiracetam MOA
binds selectively to synaptic vesicular protein modifies synaptic release of glutamate and GABA
levetiracetam uses
adjunct
partial seizures in adults and kids
primary generalized tonic-clonic seizures
myoclonic seizures of juvenile myoclonic epilepsy
levetiracetam ADRs
less common more serious mood and behavioral changes
ethosuximide MOA
reduces the low T-type CaCH threshold (thalamic pace maker)
ethosuximide uses
absence seizures
ethosuximide ADRs
gastric distress
ethosuximide DDIs
valproic acid may inhibit meta or ethosuximide
valproic acid MOA
blocks sustained high frequency firing of neurons
action against partial seizures d/t effect on Na current via bockde of NMDARs
valproic acid PK
fully ionized at body pH
highly protein bound
valproic acid uses
absence seizures myoclonic seizures generalized tonic-clonic seizures partial seizures status epilepticus bipolar migraine prophylaxis
valproic acid ADRs
GI, heartburn
fine tremor
weight gain, increased appetite, hair loss
hepatotoxic, thrombocytopenia *monitor
first line for partial seizures, including seondarily gerneralized
carbamazepine
lamotrigine
oxcarbazepine
levetiracetam
first line for primary generalized tonic-clonic
valproate
lamotrigine
levetiracetam
first line for
absence seizures
ethosuximide
valproate
atypical absence, myocloinic, atonic
valproate
lamotrigine
levetiracetam
which drugs enhance NaCh inactivation?
carbamazepine phenytoin topiramate lamotrigine valproate zonisamide
which drugs enhance GABA synaptic transmission
vigabatrin and valproate (both decrease GABA breakdown in neuron)
tiagabine (inhibit GABA transport out of cleft)
benzodiazepines and barbituates (bind GABARs)
which drugs reduce Ca current?
valproate
ethosuzimide
Stevens-johnson syndrome
asians w/HLA-B1502
topiramate MOA
NaCh
GABARs
CaChs
can also act on glutamate/NMDARs
topiramate uses
partial, generalized tonic-clonic, infantile spasms, absence seizures, migranes
topiramate ADRs
paresthesias
nervousness
weight loss
diazepam MOA
enhance GABA mediated Cl influx
diazepam MOA
extremely lipophillic
diazepam uses
status epliepticus
myoclonic
partial
generalized tonic-clonic
phenobarbital MOA
enahances GABA mediates current and decrease glutamate release
phenobarbital P
hepatic enzyme inducer
phenobarbitol uses
partial seizues
generalized tonic-clonic
what drugs mess with OBC effectiveness
carbamazepine oxcarbamazepine phenobarbital phenytoin primidone ruginamide
which drugs are teratogenic
phenytoin
valproate
topiramate
