Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
73 Cards in this Set
- Front
- Back
|
Simple partial seizures |
Consciousness preserved Convulsive jerking, paresthesias, psychic symptoms, autonomic dysfunction |
|
|
Complex partial seizures |
Impaired consciousness Preceded or accompanied by psychologic symptoms |
|
|
Tonic-clonic seizures |
Tonic phase < 1 min (abrupt LOC, muscle rigidity and respiration arrest) Clonic phase 2-3 mins (jerking of body mm, fecal/urinary incontinence, lip biting) Grand mal |
|
|
Absence seizures generalized |
Impaired consciousness sometimes with automatisms, loss of postural tone, enuresis Childhood --> Cease by age 20 Petit mal |
|
|
Status epilepticus |
series of seizures (tonic-clonic usually) without recovery of consciousness between attacks Life-threatening |
|
|
Secondary generalized seizure (action in brain) |
Starts as single locus (tonic) that acts on thalamus and causes spread throughout cortex (clonic) |
|
|
Child risk factors for epilepsy |
fever mental retardation cerebral palsy genetics |
|
|
Adult risk factors for epilepsy |
trauma tumors |
|
|
Elderly risk factors for epilepsy |
AD stroke |
|
|
Fraction of drug-R seizures |
1/3 uncontrolled |
|
|
Earliest seizure therapies |
Bromide, phenobarbital, phenytoin, valproate |
|
|
1st gen anti-seizure drugs effective against |
generalized tonic-clonic and partial seizures generalized absence seizures |
|
|
1st gen TC/partial seizure drugs MOA |
prolong inactivation of voltage sensitive Na channels (decrease activity and excitation) some potentiate GABA |
|
|
1st gen absence seizure drug MOA |
block T-type Ca channels in thalamic neurons |
|
|
drugs targeting neuropathic pain |
also work for seizures - new therapies |
|
|
formulation of most drugs |
extended release |
|
|
Barbiturates and BZs |
Potentiate opening of GABAA to stop AP in cortex |
|
|
Gabapentin MOA |
close Ca channel on axon to inhibit AP in cortex |
|
|
Phenytoin, carbamazepine, lamotrigine MOA |
Inactive voltage gated Na channel on axon for longer (prolong closure to decrease ability to excite) in cortex near locus |
|
|
Ethosuximide or valproic acid MOA |
Block T type Ca channel in thalamus |
|
|
DOCs for partial and T/C seizures |
Carbamazepine Lamotrigine Levetiracetam Valproic acid DOC due to use as monotherapy and tolerability |
|
|
Alternative drugs for partial and T/C seizures |
Phenobarbital Phenytoin Gabapentin Topiramate |
|
|
Carbamazepine |
Dampens excitability by prolonging Na channel inactivation Partial and general TC seizures |
|
|
Alternative use for carbamazepine |
Trigeminal neuralgia Bipolar disorder |
|
|
Carbamazepine metabolism |
CYP3A4 which it significantly induces (along with other hepatic enzymes) |
|
|
Carbamazepine dosing |
May have to increase dose over time because it enhances its own metabolism by inducing CYPs |
|
|
Exacerbation due to carbamazepine |
absence and myoclonic seizures |
|
|
Toxicity due to partial and general TC drugs |
Diplopia, ataxia, headache, somnolence |
|
|
Carbamazepine ADEs |
Strong induction of CYPs Stevens-Johnson Syndrome |
|
|
Risk of Stevens Johnson Syndrome for carbamazepine |
Asians with HLA-B*1502 allele |
|
|
Lamotrigine uses |
Partial TC General TC Lennox Gastaut |
|
|
Other uses for lamotrigine |
Bipolar disorder Depression in epileptic patients |
|
|
MOA for lamotrigine |
Use-dependent block of Na channel Inhibits voltage gated Ca channels to further hyperpolarize cell |
|
|
Lamotrigine metabolism |
By CYP Does not induce or inhibit CYPs! |
|
|
Levetiracetam uses |
Partial TC Generalized TC Myoclonic Lennox-Gastaut |
|
|
MOA for levetiracetam |
Binds SV2A protein on vesicles to modify and inhibit NT release |
|
|
Pharm profile for levetiracetam |
Very clean: little metabolism (most secreted unchanged by kidney) to inactive metabolite no inhibition or induction of CYPs |
|
|
Valproic acid uses |
All seizure types (partial TC, general TC, myotonic, atonic, combination) |
|
|
Alternative uses for valproic acid |
Bipolar disorder Migraine |
|
|
MOA of valproic acid |
Broad spectrum- many MOAs Block Na channels Augment GABA Histone deacetylase inhibition (increase gene expression) |
|
|
Valproic acid highly efficacious against... |
Absence seizures |
|
|
DDIs with valproic acid |
weak CYP inhibitor |
|
|
Avoid using valproic acid for: |
Pregnant/nursing women Young children |
|
|
Reason why valproic acid is not always DOC |
Rare but serious idiosyncratic hepatotoxicity Must constantly monitor liver function and avoid in young kids |
|
|
Valproate ADEs |
Few, mostly well tolerated GI effects Rarely idiosyncratic hepatotoxicity |
|
|
Phenobarbital action |
potentiate GABA DOC in infants (rapid and safe and cheap) |
|
|
Phenytoin action |
blocks Na channels dose-dep elimination by liver: requires precise plasma levels and dose monitoring to avoid zero order kinetics |
|
|
Gabapentin action |
blocks voltage gated Ca channel neuropathic pain and various other off label uses that may not have good efficacy |
|
|
Topiramate action |
Multiple MOAs - inhibits carbonic anhydrase THE hot drug for off label uses like migraine and BPD |
|
|
Topiramate ADEs |
decreased memory |
|
|
DOCs for absence seizures (block T-type Ca channels) |
Ethosuximide Valproic acid |
|
|
Alternative drugs for absence seizures |
Clonazepam Lamotrigine Levetiracetam |
|
|
Ethosuximide used only for |
Absence seizures Acts on T type Ca channel on soma |
|
|
Ethosuximide ADEs |
Very few - well absorbed, complete metabolism, dose and plasma levels well-correlated, low toxicity Dose-related GI distress |
|
|
Clonazepam use |
absence seizures |
|
|
Limits for clonazepam |
BZ ADEs: sedation, development of tolerance, withdrawal |
|
|
Status epilepticus treatment |
IV diazepam/lorazepam followed by IV fosphenytoin IM midazolam |
|
|
Antiseizure drug therapy risks |
Teratogenic and drug withdrawal |
|
|
Valproate as teratogen |
Causes spina bifidia and IQ effects |
|
|
Overall teratogen risk with antiseizure drugs |
2x increased risk of congenital malformations when on drugs (but not if off drug during pregnancy) add folate to decrease some cognitive effects |
|
|
Remission for epileptics |
Most achieve remission >5 years while on meds and 75% can be withdrawn gradually |
|
|
Withdrawal most common with |
BZs and barbiturates |
|
|
Ketogenic diet and epilepsy |
high fat diet to mimic fasting and force brain to use ketones instead of glucose **treatment refractory seizures in children with Lennox Gastaut Syndrome |
|
|
Vagus nerve stimulation for epilepsy |
drug refractory complex partial/general seizures unknown MOA but good response |
|
|
Responsive neurostimulator device for epilepsy |
implanted in brain near foci (bypasses vagus) to decrease drug refractory complex partial/general seizures |
|
|
Anterior temporal lobectomy |
Harmful and refractory PARTIAL seizures in adults seizure free for 5 years |
|
|
Corpus callosotomy |
Lennox Gastaut in children |
|
|
Hemispherectomy |
For severe childhood forms |
|
|
Future drugs for epilepsy |
Target SV2A binding, AMPA receptor antagonists, K channel activation Want to prevent epileptogenesis (stop locus from becoming seizure focus) |
|
|
Principles for managing epilepsy |
Ascertain cause Use DOC for seizure type Ensure adequate trial of a SINGLE drug (do not add more, only monotherapy - low TI and toxicity possible0 Monitor plasma levels |
|
|
Treatment failure |
Try monotherapy with another firstline drug - avoid polypharmacy If all drugs fail, consider surgery or vagal nerve stimulation |
|
|
When to do epilepsy surgery? |
ASAP after failure of 2 first line drugs (do not wait 10 years) |
|
|
Reason you may see seizures again while treating with carbamazepine |
Carbamazepine is a strong inducer of its own metabolizer CYP, so need to adjust dose to maintain appropriate therapeutic level in blood DON'T add second drug |
