Seizures B&B Flashcards
what are 4 electrolyte imbalances that can cause seizures, most often in children or elderly?
- hyponatremia
- hypernatremia
- hypoMg
- hypocalcemia
what are 5 components of seizure workup and the purpose of each?
- blood work - electrolyte imbalance can trigger seizure
- EKG - cardiac syncope can mimic seizure
- EEG - look for electrical abnormalities
- brain imaging (CT or MRI) - rule out tumor or stroke
- lumbar puncture - if infection is suspected
simple partial versus complex partial seizure
simple partial – no alteration in consciousness
Complex partial – altered consciousness
What are the four types of generalized seizures?
- absence/petite mal: staring off, blank stares
- Tonic clonic/grand mal: drop to the ground, writhing
- Atonic/drop seizure: drop, flaccid/ hypotonia
- Myotonic: rhythmic muscular contractions.
epigastric “rising” sensation is an autonomic symptom of seizures that is a common aura with ______ epilepsy
common aura with medial temporal lobe epilepsy
Jacksonian seizure
seizure aura of muscle jerking (simple partial seizure affecting motor cortex)
how do patients in the post-ictal state present?
transition period after a seizure in which brain recovers
patients show confusion and lack of alertness. Common focal neurological deficits may be present, variable time (mins-hours)
Helps differentiate seizure from cardiac cause - patients are immediately aware of their surroundings after regaining consciousness from cardiac problem
what is the most common site of partial seizures?
temporal lobe
many patients have mesial temporal sclerosis (hippocampal sclerosis) - lose neurons in hippocampus
mesial temporal sclerosis
aka hippocampal sclerosis - lose neurons in hippocampus
predisposes patients to temporal lobe seizures
often bilateral but one side more affected, can diagnose by MRI (looks like lesion in hippocampus)
how does juvenile myoclonic epilepsy present?
hallmark: myoclonic jerks on awakening from sleep, often presenting as shock-like irregular movements of both arms
absence seizures develop first (5yo) —> myoclonic seizures (15yo) —> grand mal seizures
child presenting with myoclonic jerks on awakening from sleep, often shock-like irregular movements of both arms =
juvenile myoclonic epilepsy
absence seizures develop first (5yo) —> myoclonic seizures (15yo) —> grand mal seizures
what is the prognosis of childhood absence epilepsy?
recurrent absence seizures (no change in body/motor tone) lasting a few seconds, NO post-ictal confusion
good prognosis, usually remits by puberty
A child is brought to the pediatrician by their parents, who are worried their child has an attention disorder. At parent teacher conferences, the child’s teacher said the child often stares off into space at class and is not paying attention. The teacher said they do this frequently, staring off for a few seconds before returning to focus. What could this be?
childhood absence epilepsy: recurrent absence seizures (no change in body/motor tone) lasting a few seconds, NO post-ictal confusion
good prognosis, usually remits by puberty
what is the classic EEG finding of childhood absence epilepsy?
2.5-5 Hertz spike wave activity superimposed on normal background EEG
recurrent absence seizures (no change in body/motor tone) lasting a few seconds, NO post-ictal confusion, usually remits by puberty
what does the following EEG finding indicate:
2.5-5 Hertz spike wave activity superimposed on normal background EEG
childhood absence epilepsy: recurrent absence seizures (no change in body/motor tone) lasting a few seconds, NO post-ictal confusion, usually remits by puberty
what is the treatment for childhood absence epilepsy?
recurrent absence seizures (no change in body/motor tone) lasting a few seconds, NO post-ictal confusion, usually remits by puberty
rx: ethosuximide is first line: blocks thalamic T-type Ca2+ channels
what is the mechanism and clinical use of ethosuximide?
first line tx for childhood absence epilepsy: blocks thalamic T-type Ca2+ channels
how do febrile seizures present in children? what is the prognosis?
common (2-4%) in children <5yo
Child loses consciousness, shakes – children at risk for more febrile seizures. However, overall prognosis is generally good (most kids outgrow them)
Not considered epilepsy
What is the treatment for seizures due to eclampsia?
magnesium sulfate (MgSO4) - only used for seizures due to eclampsia
status epilepticus
continuous seizure lasting more than 30 mins OR seizures that recur less than every 30 mins
medical emergency, can cause arrhythmias, lactic acidosis, HTN
what is the first line treatment for breaking seizures in status epilepticus? give drug class and DOC name
benzodiazepines - rapid acting, Lorazepam is DOC
Lorazepam is a _______ and is the DOC for ______
Lorazepam is a benzodiazepine and is the DOC for status epilepticus
Lorazepam (benzodiazepine) is DOC for breaking status epilepticus. If that is not working, _____ or _____ will be administered to prevent recurrent seizures. If patients are still seizing, ______ can be tried. If that doesn’t work, general anesthesia + intubate.
Lorazepam (benzodiazepine) is DOC for breaking status epilepticus. If that is not working, phenytoin (PO) or fosphenytoin (IV) will be administered to prevent recurrent seizures.
If patients are still seizing, phenobarbital can be tried. If that doesn’t work, general anesthesia + intubate.
what are the 2 categories of drugs used to prevent seizures?
-
sodium inactivators: block channels —> less neuron activity
(ex: phenytoin, carbamazepine, lamotrigine, valproic acid) -
GABA activators: inhibitory NT
(phenobarbital, tiagabine, vigabatrin, also valproic acid)
[and of course there are drugs that work by other mechanisms not in these categories]
status epilepticus is always treated with _____
absence seizures are always treated with ______
status epilepticus is always treated with benzodiazepines
absence seizures are always treated with ethosuximide
what is the most teratogenic anti-epileptic drug?
valproic acid: 1-3% chance of neural tube defects (spina bifida)
what type of anti-epileptic drug is carbamazepine, and which types of seizures is it used for?
Na+ channel inactivator - used for partial and generalized seizures, also used for bipolar disorder and trigeminal neuralgia
MANY side effects
[A very PALE (anemic) man FELL OVER (ataxia) after DRINKING too much (liver toxicity) eating too many CARBS (carbamazepine) and was awoken by his friend STEVE (Stevens-Johnsons) who gave him a big bottle of WATER (SIADH)]
what are the clinical uses of carbamazepine? (4)
Na+ channel inactivator
- partial seizures
- generalized seizures
- bipolar disorder
- trigeminal neuralgia
MANY side effects!
what are the side effects of carbamazepine (used to treat seizures, bipolar disorder, and trigeminal neuralgia)? (6)
- diplopia, ataxia
- low blood counts/ bone marrow suppression - agranulocytosis, aplastic anemia, low WBC, low platelets (must monitor CBC)
- liver toxicity (must monitor LFTs)
- SIADH
- Stevens-Johnson syndrome (rash)
- hyponatremia
[A very PALE (anemic) man FELL OVER (ataxia) after DRINKING too much (liver toxicity) eating too many CARBS (carbamazepine) and was awoken by his friend STEVE (Stevens-Johnsons) who gave him a big bottle of WATER (SIADH)]
what side effects are associated with ethosuximide? (4) What is this DOC for?
blocks thalamic T-type Ca2+ channels, DOC for childhood absence seizures
adverse effects:
1. Stevens-Johnson syndrome
2. N/V
3. sleep disruption
4. fatigue, hyperactivity
what is the MOA of phenobarbital? what are the associated adverse effects (2 symptoms, 1 contraindication, 1 drug-drug interaction)?
barbiturate: GABA activator (holds Cl- channel open), anti-epileptic
adverse effects:
1. myocardial/respiratory depression
2. CNS depression (esp. w/ alcohol!!)
3. contraindicated in porphyria (heme disorder) - causes attacks of abdominal pain
4. induces P450
which 3 anti-epileptic drugs induce CYP450?
- carbamazepine
- phenobarbital
- phenytoin
recall induction of CYP450 causes drug levels to fall
which 2 drugs that are metabolized by P450 are still used sustainably today, and must be monitored for interaction with drugs which inhibit P450?
- statins - combo with P450 inhibitor causes rhabdomyolysis
- warfarin
ex of P450 inhibitors: isoniazid, erythromycin, cimetidine, cyclosporin, azole antifungals, grapefruit juice, ritonavir (HIV)
[many P450 drugs are rarely used anymore - theophylline, cisapride, terfenadine, etc]
which of the following is NOT a P450 inhibitor?
a. isoniazid
b. erythromycin
c. phenobarbital
d. azole antifungals
e. grapefruit juice
f. ritonavir (HIV)
c. phenobarbital
many anti-epileptic drugs are P450 inducers - cause there to be more metabolism of drugs
other inducers include: chronic EtOH, rifampin, carbamazepine, phenytoin
for which type of seizures is phenytoin very useful?
Na+ channel inactivator, very useful for tonic-clonic seizures
what adverse effects are associated with phenytoin (Na+ channel inactivator, treats tonic-clonic seizures)? (7)
- gingival hyperplasia
- rash
- folic acid depletion
- decreased bone density
- long term: nystagmus, diplopia, ataxia
- teratogenic
- hirsutism, facial coarsening
[PENNY (phenytoin) was a very WEAK (decreased bone density) girl trying to lift a heavy weight so hard that she got RED IN THE FACE (rash), BORE HER TEETH (gingival hyperplasia), and CROSSED HER EYES (diplopia)]
describe the special metabolism of phenytoin (anti-epileptic)
dose-dependent hepatic metabolism - at low dose, there is a small increase in blood levels (first-order kinetics); at high dose, enzymes are saturated and there is a rapid increase in blood levels —> dose increments of equal size produce disproportional rise in steady-state plasma concentration (zero-order kinetics)
phenytoin induces but is also metabolized by P450! must monitor drug levels (oral contraceptives, warfarin, carbamazepine - caution with combination therapy!)
describe the MOA (3) and clinical use of valproic acid (2)
MOA:
1. Na+ channel inactivator
2. GABA activator
3. inhibits T-type Ca2+ channels
clinical uses: anti-epileptic + mood stabilizer (bipolar, acute mania)
adverse effects: TERATOGENIC (spina bifida!), N/V, hepatotoxic, tremor, weight gain
what kind of drug is levetiracetum, and what is its brand name?
aka Keppra: VERY effective anti-epileptic drug
exact mechanism unknown, useful for many types of seizures, drug titrated to clinical effect, well tolerated
Lamotrigine
Na+ channel inactivator, broad-spectrum anti-seizure
caution: can cause Stevens-Johnson syndrome
MOA and clinical use of Gabapentin
aka Neurontin
affects calcium channels (NOT GABA! they were wrong oh well)
used for seizures and neuropathies
can cause sedation and ataxia
MOA, clinical use (2), and adverse effects (4) of topiramate
MOA: Na+ channel inactivator AND GABA activator
clinical use: seizures AND migraines
adverse effects: sedation, weight loss, kidney stones (weak carbonic anhydrase inhibitor)
clinical uses of primidone (2)?
mechanism unclear, but metabolized to phenobarbital
- seizures
- essential tremor
what are the 3 stages/degrees of focal onset seizures?
- focal aware
- focal with impaired awareness
- focal onset to bilateral tonic-clonic
what are the 4 phases of generalized seizures?
- aura - peculiar sensation, dizziness, strange smell, numbness
- tonic phase - rigid muscle contraction, open eyes with dilated pupils (30-60s)
- clonic phase - rhythmic, jerking contraction and relaxation of all muscles (generalized convulsion), frothing at mouth, tongue biting, incontinence (several minutes)
- post-ictal state - drowsiness, confusion, or coma due to neural depression (several hours)
contrast presentation of childhood absence epilepsy with juvenile myoclonic epilepsy
childhood absence epilepsy: ages 4-10, staring spells and arrested activity lasting ~10 seconds, EEG shows 2.5-3 Hz spike and wave discharges, tx = ethosuximide
juvenile myoclonic epilepsy: ages 12-18, myoclonus when awakening, exacerbated by sleep deprivation and alcohol, EEG shows 4-6 Hz irregular spike-waves and poly-spike waves (PSW)
Benign Rolandic Epilepsy
aka childhood epilepsy with centrotemporal spikes
ages 4-15, infrequent seizures occurring during sleep
present with sensorimotor phenomena of face —> hyper-salivation, jaw contraction, speech arrest, etc
most kids outgrow it
what is the triad of West Syndrome?
- infantile spasms
- delay in development
- hypsarrhythmia on EEG
how do infantile spams present? how are they treated?
3-12 months old, idiopathic
spasms occur in clusters of briefly sustained movements of axial musculature (most commonly flexors), commonly upon awakening (sleep-wake transition), EEG shows chaotic high-amplitude and multi-focal spikes
tx: ACTH or prednisone
Sandifer Syndrome
occurs in early childhood with intermittent spells of stiffening associated with feedings - pediatric manifestation of gastro-esophageal reflux
seen in neuro-developmentally normal children, normal EEG
treat with anti-reflux medications
what are stereotypies?
Nonpurposeful, intermittent, and repetitive movements or
behaviors, usually seen in neurologically impaired children
Head shaking, head nodding, rocking movements, jumping,
tongue thrusting, chewing, hyperventilation, hand shaking and
tonic postures, etc
generally improve over time
what does EEG of syncope vs seizures show?
syncope - high voltage delta flattening of EEG
seizures - spike waves on EEG
what is a more soluble form of phenytoin (Dilantin) which can be administered IV?
phenytoin = Na+ channel inhibitor, anti-seizure drug
fosphenytoin: prodrug of phenytoin, designed for parenteral use
for which types of seizures is phenytoin (Dilantin) contraindicated? (2)
may exacerbate
1. myoclonic seizures
2. absence seizures
how does phenytoin (Dilantin) travel through the body?
Na+ channel inhibitor, anti-seizure
90% bound to plasma protein, but only free phenytoin can penetrate BBB
therefore, hypoalbuminemia can impact plasma levels (increased proportion of active drug)
what are the contraindications (3) of carbamazepine (Tegretol, Carbatrol)?
Na+ channel inhibitor, anti-seizure
- exacerbates absence or myoclonic seizures
- blood disorders
- liver disorders
describe the pharmacokinetics of carbamazepine (Tegretol, Carbatrol) - what is the clinical significance of this?
75% protein-bound, t1/2 falls significantly over first few weeks of therapy due to induction of hepatic enzymes (CYP) that metabolize itself - ”autoinduction”
patients who respond well to initial therapy may be mistakenly considered refractory if auto-induction phenomena is not taken into account
which patients are at most risk of developing carbamazepine-induced Stevens-Johnson syndrome? What is the specific allele that causes the predisposition?
carbamazepine = anti-seizure Na+ channel inhibitor
incidence of Stevens-Johnson highest in Asian patients due to HLA allele B1502
patients with Asian ancestry should be screened for HLA B1502 before initiating tx w/ carbamazepine
name 2 newer derivatives of carbamazepine (Tegretol, Carbatrol) with fewer adverse effects and NO auto-induction of CYP enzymes
- OXcarbazepine
- ESLIcarbazepine
what are the indications of valproic acid/ valproate (Depakote)?
broad spectrum anti-seizure drug
- focal and generalized seizures
- absence, myoclonic, and atonic seizures
- photosensitive epilepsy, juvenile myoclonic epilepsy
ok so like everything got it
describe the pharmacokinetics of valproate (depakote) - looking for 3 points here
90% protein bound and can displace other drugs from albumin
crosses the placenta —> highly teratogenic! (spina bifida!)
hepatic elimination and inhibits hepatic enzymes - caution with combination therapy of other anti-seizure drugs! (INCREASES plasma concentration)
what are the adverse effects of valproate (Depakote)? (6)
- N/V, tremor, sedation, ataxia - transient symptoms
- alopecia
- weight gain
- thrombocytopenia
- hepatotoxicity - monitor LFTs
- teratogenic NEURAL TUBE DEFECTS - esp. spina bifida
what are 2 other clinical uses of valproate besides seizures?
broad spectrum anti-seizure + migraine prophylaxis and bipolar disorder
what are the mechanisms of action of lamotrigine (Lamictal)? (3)
broad spectrum anti-seizure
- Na+ channel inhibition - prolongs inactive state
- inhibits synaptic release of glutamate
- inhibits voltage-gated Ca2+ channels
what are the adverse effects of ethosuximide (Zarontin)? (3)
DOC for absence seizures (inhibit thalamic T-type Ca2+ channels)
- GI distress (N/V, pain)
- urticaria, possible Stevens-Johnson syndrome
- leukopenia, thrombocytopenia, pancytopenia, aplastic anemia
what is the mechanism of benzodiazepines and barbiturates?
enhance GABA(A) receptor-mediated inhibition of action potentials by enhancing influx of Cl-
benzodiazepines - increase frequency of receptor opening
barbiturates - prolong receptor opening
what is the MOA and clinical use of phenobarbital (Luminal)?
binds GABA(A) receptor, prolonging chloride influx
indicated for all seizure types, especially those difficult to control (status epilepticus)
relatively low toxicity and low cost
describe the pharmacokinetics of phenobarbital (Luminal)
indicated for all seizure types, esp. difficult to control (status epilepticus) - binds GABA(A) receptor to prolong chloride influx
metabolized by hepatic enzymes (CYP), also induces hepatic enzymes (CYP and UGT isozymes) —> drugs metabolized by these (oral contraceptives) will be more rapidly degraded
_____ is a prodrug that is metabolized to phenobarbital in the body
primidone is a prodrug that is metabolized to phenobarbital in the body
what is the mechanism of action of diazepam (Valium), lorazepam (Ativan), clonazepam (Klonopin), and clobazam (Onfi)?
what are the adverse effects?
benzodiazepines: bind to GABA(A) receptor and increase frequency of chloride channel opening
adverse effects: sedation, dependence, CNS depression (risk of cardio-respiratory depression), behavioral disturbances
limited by sedation, tolerance, and dependence
treat seizures, anxiety disorders, insomnia, NMJ disorders
diazepam (Valium) and lorazepam (Ativan) are first line for…
what kind of drugs are these?
benzodiazepines: bind to GABA(A) receptor and increase frequency of chloride channel opening
first line for status epilepticus
name 2 drugs which are first line for status epilepticus
diazepam (Valium) and lorazepam
benzodiazepines: bind to GABA(A) receptor and increase frequency of chloride channel opening
what is the MOA and clinical use of tiagabine (Gabitril)?
GABA analog which inhibits GAT-1 GABA transporter —> reduces reuptake of GABA
used as adjunct therapy for focal seizures, off-label use for bipolar disorder, anxiety, neuropathic pain
what is the MOA and clinical use of vigabatrin (Sabril)? which adverse effect should be monitored?
GABA analog which inhibits breakdown of GABA by targeting GABA transaminase
used as adjunct therapy for refractory complex focal seizures and monotherapy for infantile spasms
watch for renal toxicity!
what is the MOA and clinal use of gabapentin (Neurontin) and pregabalin (Lyrica)?
designed to be GABA analogs BUT ACTUALLY INHIBIT VOLTAGE-GATED CA2+ CHANNELS containing alpha2delta1 subunit
used as adjunct therapy for focal and secondarily generalized seizures, also prescribed for neuropathic pain (fibromyalgia)
what is the MOA and clinical use of levetiracetam (Keppra)?
binds synaptic vesicle protein 2A (SVP2A) protein and inhibits NT release
treats focal seizures (monotherapy), Lennox-Gastaut syndrome, primary generalized tonic-clonic seizures
renal clearance - contraindication with renal dysfunction
what is the MOA and clinical use of perampanel (Fycompa)?
non-competitive antagonist of glutamate - binds AMPA receptor
new drug, adjunct therapy for adults with focal seizures and generalized tonic-clonic seizures
black box warning of serious psychiatric/behavioral adverse reactions — reserve for use after failure of other drugs
what is the treatment protocol for status epilepticus?
- treat initially with benzodiazepine — lorazepam or diazepam via IV preferential
- followed fosphenytoin or phenobarbital
this treatment is done for any seizure lasting >5 minutes
