anticonvulsants 49/50 Flashcards
Phenobarbital (Luminal®)
anti epileptic drug: barbiturate, original, cheap, effective
tonic-clonic and partial seizures
potentiation of synaptic inhibition via GABAa receptor
Phenytoin (Dilantin®, Diphenylan®)
anti epileptic drug
monotherapy generalized tonic-clonic and partial seizures
Block of voltage gated sodium channels (promote inactive state)
zero-order kinetics
Carbamazepine (Tegretol®, Carbatrol®)
anti epileptic drug
Block of voltage gated Na+ channels (promote inactive state)
monotherapy generalized tonic-clonic and partial seizures (also used in manic-depressive patients)
self-induced metabolism, also, metabolism increased by pheonbarb/phenytoin
Ethosuximide (Zarontin®)
anti epileptic drug
mono therapy for absence seizures (altered Ca2+ channel function in thalamus)
Block of T-type calcium channels located on the postsynaptic membrane (thalamus)
Valproic acid (Depakote®, Depakene®)
anti epileptic drug
monotherapy, tx both absence and tonic-clonic seizures (ALL)
Block of voltage gated Na+ channels (promote inactive state)
AND
Block of T-type calcium channels located on the postsynaptic membrane
increases GABA synthesis
(off-label uses)
Fosphenytoin (Cerebyx®)
anti epileptic drug
water-soluble pro-drug of phenytoin used for treating status epileptics (given IV)
Gabapentin (Neurontin®)
Newer anti epileptic drug
GABA molecule bound to lipophillic hexane ring (crosses BBB)
DOES NOT actually interact with GABA receptor, but suppress neuronal activity
binds to L-type Ca channels
Adjunctive tx partial +/- genalized secondary seizures; but mostly used for neuropathic pain
**Not metabolized, excreted unchanged in urine (RFTs before tx)
SE: fatigue, ataxia
(similar drug: Pregabalin (Lyrica®))
Oxcarbazepine (Trileptal®)
Newer anti epileptic drug
Block of voltage gated Na+ channels (promote inactive state)
monotherapy/adjunctive treatment partial seizures
like carbamazepine, but does not auto induce, but still incr. metabolism of OCTs
Lamotrigine (Lamictal®)
Newer anti epileptic drug
Monotherapy and adjunctive treatment partial- and generalized tonic/clonic seizures; LGS. Considered a “broad spectrum” AED
prolong rate of recovery of voltage-gated Na+ channels from inactivation, inhibit Ca to lesser extent
Topiramate (Topomax®)
Newer anti epileptic drug
Monotherapy and adjunctive therapy for partial and tonic/clonic seizures, LGS. Considered a “broad spectrum” AED
Inhibit Na channels and AMPA-kainate receptors enhance GABA receptors
Levetiracetam (Keppra®)
Newer anti epileptic drug
Adjunctive treatment for partial- and tonic/clonic seizures in adults and myoclonic seizures in children; IV preparation for status epileptics
may prevent presynaptic glutamate release
highest safety margin
highest therapeutic index
3-D “printable” drug
simple partial seizure
single site within the cortex
preservation of consciousness, short duration 20 – 60 sec
focal motor (e.g. one side of face may twitch) Jacksonian (“marching” seizure, e.g. muscle twitching “running” up the arm) somatosensory (varied responses; smelling sulfur, crawling sensation on skin, narrowing of visual field)
complex partial seizure
single site within the cortex
gradual loss of consciousness, 30 sec – 2 min
may begin with simple seizure, hallucination, strong emotions followed by automatisms (lip smacking, hand wringing, etc)
EEG can determine ??
type of seizure
Of the ~10 electrodes placed on the head for an EEG:
if only 1-2 electrodes display synchronous activity during seizure, what type ??
all EEG electrodes will display synchronous activity during a ??
partial seizure
generalized seizure
if all EEG electrodes display synchronous activity during a seizure
generalized seizure
generalized seizure
simultaneously in both hemispheres of brain (40% of all seizures)
absence (generalized)
sudden loss of consciousness, less than 30 sec
staring and blinking (3/sec)
body may remain active
ADHD, impaired learning
tonic-clonic (grand mal, gen)
sudden loss of consciousness, 1.5 to 2.5 min
20 sec of muscle rigidity followed by 1 – 2 min of rhythmic muscle contractions (clonic)
injury when falling during tonic stage, loss of bowel control
Phenobarbital (Luminal®) SEs
sedation, irritability/hyperactivity (kiddos), rash
*metabolized by CYP2C9, induction of CYP3A4–> inc. metabolism of OCTs and teratogenic
anticonvulsant drug MOA
reduce neuronal activity
drugs that enhance inhibitory effects of GABA
Barbs (Phenobarbital and primidone) and benzos (clonazepam, diazepam) increase GABA effects at GABAa
tiagabine: inhibit the re-uptake of GABA
vigabatrin: irreversible inhibitor of the GABA-degrading enzyme GABA transaminase
monotherapy will sufficiently control seizures for
70% of epileptic pts
original seizure tx
bromides
barb less effective than phenobarbital
SEs??
primidone
dizziness, nausea, nystagmus, ataxia (dec. firing)
Phenytoin SEs
gingival hyperplasia
SJS: only in first few months of tx
interact with warfarin and OCTs and may cause birth defects
Carbamazepine SEs
Acute: stupor, coma, hyperirritability convulsions
Chronic: drowsiness, vertigo, ataxia, blurred vision. Induces CYP3A4 resulting in increased drug metabolism (e.g. oral contraceptives)
benzos can be used for ??
adjunctive treatment only of absence seizures and juvenile myoclonic seizures
newer AEDs
lack serious side effects (less SJS)
do not induce liver enzymes (fewer drug-drug interactions)
less efficacious
mostly approved for adjunctive treatment (combo tx)
Lennox-Gustaut syndrome
Childhood-onset epilepsy
Severe cognitive dysfunction
Multiple seizure types including atonic or “drop” seizures (cause of injury)
Resistant to drug therapy (tx with Felbamate)
Mortality rates 3 – 7%
ketogenic diet
partial seizure tx
(or secondarily
generalized)
carbamazepine
phenytoin
alternative: lamotrigine (broad-spec)
valproic acid
generalized: absence seizure tx
Ethosuximide
Valproic acid*
alternative: Clonazepam
generalized: tonic-clonic tx
Carbamazepine
Phenytoin
Valproic acid*
alternatives:
Lamotrigine*
Topiramate*
Status Epilepticus
a series of seizures (any type) where full recovery from one seizure does not occur before onset of next seizure
20% mortality rate
Status Epilepticus tx
lorazepam IV
IV fosphenytoin (Cerebyx®) (water soluble prodrug of phenytoin-which would irritate veins)
levetiracetam (alternative to fosphenytoin)
phenobarbital and valproic acid (Depacon®)
long term use of AEDs may cause
osteoporosis:
altered vitamin D metabolism in the liver–>lower bone density
AEDs: OCT interactions
safe for preggos??
specifically ??
most common offending drug ??
3X higher failure rate of the contraceptive
NO, 2 – 3 fold increase in birth defects
neural tube formation abnormalities resulting in facial and cranial deformities
phenytoin (all AEDs may cause similar birth defects)
To reduce the likelihood of neural tube birth defects the patient should be given ???
folate (0.4 mg/day) throughout pregnancy
vitamin K (10 mg/day) during last month of gestation to help reduce newborn blood coagulation problems/Vit K deficiencies
treating epilepsy with ??? is controversial
generic drugs, use brand names
teratogenic AED
valproic acid
for pregnant/soon to be pregnant pts…
do not discontinue tx (do not want break thru seizures)
but reduce to mono therapy and monitor drug plasma levels/seizure activity, lowest dose possible is desired
ethosuximide SEs
Nausea, vomiting, anorexia
CNS drowsiness, lethargy, euphoria
SJS, aplastic anemia
Valproic acid SEs
GI nausea, anorexia
CNS sedation, ataxia, tremor
Increase in hepatic blood enzymes (40%)
Hepatic toxicity in patients
Lamotrigine SEs
dizziness, ataxia, blurred vision, nausea
Rash and SJS when used in addition to other AEDs
Topiramate SEs
Ataxia, fatigue, somnolence, weight loss
Reduces plasma levels of estradiol and oral contraceptives
Levetiracetam SEs
somnolence, dizziness, asthenia , no drug-drug interactions

