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78 Cards in this Set
- Front
- Back
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MOA: sodium channels (reduces influx)
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cabamazepine
phenytoin topiramate lamotrigine valproate zonisamide oxcarbazepine felbamte rufinamide lacosamide in addition binds to CRMP-2 |
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MOA calcium channels (reduces influx)
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valproate
ethosuximide zonisamide felbamate oxcarbazepine lamotrigine topiramate pregabalin gabapentin |
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MOA: GABA transmission and channels
(GABA increases membrane hyper-polarization and seizure threshold: inhibitory) |
benzodiazepine
valproate felbamate topiramate barbiturate gabapentin pregablin tiagabine vigabatrin |
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MOA: glutamate transmission and channels (excitatory)
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lamotrigine blocks glutamate release
pregablin enhances glutamic acid decarboxylase-reducing release of glutamate felbamate blocks NMDA receptor topiramate blocks kainate receptor |
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AEDs simple and complex partial and tonic clonic
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CBZ
GBP LEV LTG PB PHT TGB TPM ZNS |
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AEDs for Lennox Gastaut
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BZ
FBM LTG TGB TPM |
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AEDs for infantile spasms
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BZ
FBM LTG TGB TPM VGB |
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AEDs for absence
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ESM
LTG PHT and CBZ should NOT be used |
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ADEs for tonic clonic
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PHT
TPM LTG ZNS |
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AEDs for Myoclonic
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BZ
FBM TPM ZNS |
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broad spectrum
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VPA
LEV (not absence) LTG (not myoclonic) |
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Drug comparison in partial seizure group (VA coop study 118)
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phenytoin, carbamazepine are more efficacious than either primadone or phenobarbital; differences due to tolerability not efficacy
efficacious=efficacy/tolerability |
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drug comparison in partial seizure group (VA Coop study 118)
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at 12 months of AED tx, only 65% of patients care continuing therapy
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drugs study in tonic clonic seizures (VA coop study 118)
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phenytoin or carbamazepine or phenobarbital are more efficacious than prima done in tonic-clonic szs, differences are due to tolerability not efficacy
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carbamazepine and valproic acid in complex partial seizures (VA coop study 264)
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carbamazepine is more efficacious than valproic acid in complex partial seizures
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VPA and CBZ in generalized tonic clonic seizures (VA coop study 264)
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VPA is more efficacious than CBZ in generalized tonic clonic seizures.
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drug study in new onset geriatric epilepsy
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randomized, double blind study in new onset geriatric epilepsy: gabapentin or lamotrigine are more efficacious than carbamazepine IM (CBZ is much less used o pts with partial seizures b/c it knocks its out,many side effects)
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ethosuximide, VPA, lamotrigine study in childhood absence epilepsy
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ETX and VPA are more efficacious than LTG in childhood absence epilepsy and ETX had the least adverse effects attentional effects
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AEDs mono therapy old and new drugs
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considering old and newer AEDs in mono therapy, the best Sz freedom rate achieved is 70-75%, with diminishing returns after the 3rd AED
25% of pts are refractory from the get-go |
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AED safety older vs. newer drugs
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less idiosyncratic drug reactions for newer drugs but they still have side effects.
CNS effects occur with most AEDs |
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Carbamazepine black box warning
(important slide) |
aplastic anemia, agranulocytosis
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VPA black box warning
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hepatotoxicity
teratogenicity pancreatitis |
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Phenytoin injection black box warning
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administer slowly not to exceed 50mg/min
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Lamotrigine black box warning
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serious rash (hospitalization and death) dosing too fast
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Felbamte black box warning
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aplastic anemia, hepatic failure
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Vigabatrin black box warning
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visual field defects/constriction, risk of vision loss with too long therapy
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gum hyperplasia with chronic tx of phenytoin
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common in younger pts with poor dental hygiene
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FDA finds evidence for ADE suicide association
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an advisory board voted against black box warning on AEDs labels
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AEDs with nonlinear pharmacokinetics concave up
(daily dose vs. serum concentration) |
PHT
ZNS? |
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AEDs with linear pharmacokinetics
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clearance remains constant as dose increases
TGB FBM TPM VGB ZNS? CBZ? OXC LEV |
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AEDs with nonlinear pharmacokinetics concave down
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clearance increases with dose: VPA, LTG?
absorption decreases with dose GBP |
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Phenytoin bioavailability after switching among brands
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small changes in the extent go phenytoin bioavailability after switching among brands, can impact total serum phenytoin concentration
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substantial changes in actual steady state total serum phenytoin concentration can occur, when comparing PHT formulations with small bioavailability differences
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narrow therapeutic index and nonlinear PHT kinetics magnify the effect that small changes in extent of PHT bioavailability has on steady state serum
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Effects of older AEDs on newer AEDs
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hepatic microsomal enzyme inducers (accelerates metabolism) include
PHT CBZ Pb Phenobarb (Mysoline) |
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Effects of newer on older AEDs
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Effects of newer on older AEDs are slight
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Effects of older AEDs on other drugs post stroke
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phenytoin and warfarin is a stinker
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Extended release AED formulations: what is the goal?
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improve medication compliance
minimize peak-to trough AED concentrations decrease peak related AEs regimen simplification and improve QOL increase efficacy by permitting an increased total daily mg dose of the AED (increase AUC drug exposure) assuming increasing efficacy is related to increasing AUC |
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CBZ IR to ER conversion: impact on CNS toxicity
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its with partial onset seizure undergoing CBZ IR for 1 year then switch to ER
CNS toxicity reduced to 25% with ER |
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Comparative absorption profiles for 5 distinct VPA/Divalproex formulations
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ER has lower peak and mean VPA concentration decreases more slowly
Depakene syrup starts steep and decreases rapidly depakene capsule, depakote sprinkes and depakote DR increase slowly, reach max, then decrease slowly but have different profiles |
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HIgher plasma VPA vs. low VPA
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Higher plasma VPA produces a greater reduction in median seizure (CPS and SGTC)frequency vs. low VPA
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XR curve (concentration vs. time)
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Once daily, extended release AEDs permit smoother, flatter curves
allows more drug per total body kg if more drug is better |
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ER, EC divalproex
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considering all total daily mg doses of divalproex, ER is most suitable for QD dosing
EC delayed release is dosed once daily high roller coaster levels can occur. lag time then concentration goes up and down rapidly in concentration vs. time curve |
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Intractability
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claim that the AED doesn't work
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Factors to consider in the definition of intractability
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was the pt diagnosis confirmed?
was the pt given an adequate AED dose? How many AEDs have been tried? (have optimal serum AED concentration been achieved?, have pharmacokinetic factors been ruled out?, what if the patient is sz free only at the supratherapeutic dose?) How many seizures per unit of time? (is 1 breakthrough sz intractability?) |
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Pearls for the community and hospital l pharmacists
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look for concomitantly used drugs that may be causing szs; DDIs are not contraindications to therapy- VPA+LTG used intentionally despite risk of SJS
be aware of the p'kinetic effects of the withdrawal of EI AEDs IM and ER formulations are nor freely interchangeable be aware of suicidality data associated with AEDs: urge ur pt to continue AED adherence Pharmacists may want to double check with prescribing MD regarding generic vs branded AED Recognize that many its are receiving AEDs for diagnoses other than szs/epilepsy-bipolar disorder, headache, weightless, various pain disorders |
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seizure and epilepsy
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both have abnormal, excessive neuronal electrical discharges
usually brief: 10-120s self limited clinical manifestations depend on part of brain involved and neuronal firing pattern |
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seizure- situational
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occurs x1 or x2?
is circumstantial as part of an acute illness or temporary cause: head trauma, febrile illness, drugs/toxins, substance/etOH withdrawal, sleep deprivation, electrolyte disorders, hypoglycemia, lightning strike NOT expected to recur when cause resolves |
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epilepsy
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occurs x1, continuously such as status epileptics
occurs x1, briefly and has +EEG or +CT/MRI lesion occurs x2 separated in time recurrent seizures over time usually spontaneous cause may be known or unknown |
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classes of meds that can provoke or worsen seizures
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antidepressants
antipsychotics anti-epileptics local and general anesthetics ethanol antimicrobials antineoplastics bronchodilators sympathomimetics analgesics others |
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Overall incidence of convulsive disorders: the bimodal distribution with increased frequency at extremes of age
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age vs. incidence curve
increases incidence before 10 and after 65 |
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international classification of seizures
Partial onset |
szs begin in a focal area of brain as defined clinically or by EEG
patient may be aware of onset (aura) |
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International classification of seizures
Generalized onset |
szs appear to begin in brain everywhere at once, bilateral EEG discharges
immediate loss of conciousness |
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simple partial seizure
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no loss of consciousness
focal, unilateral electrical discharge motor, somatosensory, psychic, visual, or autonomic features depending on brain location no postictal confusion |
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complex partial seizure
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altered consciousness
temporal/limbic electrical discharge 80% blank stare, unresponsiveness autometisms: picking, lip smacking... duration 30-120s postictal confusion |
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partial seizure with secondary generalization
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begins as simple partial or complex partial
electrical discharge generalizes to both hemispheres terminates as tonic-clonic convulsion |
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Absence seizure
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immediate loss of consciousness
blank stare, 5-20s usually no loss of body tone 3/sec hertz generalized spike-wave on EEG no postical confusion |
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generalized tonic clonic seizure
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immediate loss of consciousness unless begins as a partial
15sec hz spike tonus: flexion, extension, cry clonus: rhythmic, jerking, bilateral frequently both clonic and tonic duration 60-120s postictal confusion and exhaustion very common |
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Myoclonic seizure
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sudden, brief, shock-like jerk
head and upper body, bilateral generalized polyphasic spike wave dropping objects might occur ex: juvenile myoclonic epilepsy but can occur in adults |
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Seizure cause mortality and morbidity
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injuries of all sorts-very common
sudden death-uncommon anxiety and dread-when will it happen? social restrictions: driving, work, school, interpersonal secondary psychological problems: depression, dependency |
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seizure 1st aid
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protection from injury- 1st do no harm
1. do not restrain pt 2. do not interfere with movements 3. do not force objects btw pt's teeth 4. protect head from injury 5. protect airway from secretions-pt will NOT swallow their tongue, bite it yes psychological support obtain medical assistance if seizures recur if sz lasts about 5 mins call 911 if sz lasts 1 min, no response then back sz call 911 |
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taking a seizure history
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determine what kind of seizure:
. what do seizures look like? . what happens 1st? note eyes and aura . does pt know? aura . how long do they last? . right sided, left sided or generalized? . time to recovery and characteristics . does pt remember? have they had continuos szs causing a trip to hospital? . do they keep a sz diary? look at it Determine what kind of epilepsy |
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Taking an AED history
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Determine what AEDs are used
. currently? can they name or describe? . how does pt take them? . how adherent? . are szs controlled? . what AEs are they experiencing if any? .AEDs taken in the past? when and why d/c? AEs or inefficacy . what do they willing to tolerate in terms of efficacy vs. side effects? . any new non-AEDs meds, OTCs, herbals recently? |
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various tx modalities for epilepsy
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factor avoidance- avoid alcohol/drug of abuse, lack of sleep, strict dieting, certain light conditions
Meds- 100% of its surgery, from partial resection to hemispherectomy- 10% are candidates ketogenic diet: useful but difficult to enact, in absence szs complementary/herbal supplements with antiseisure properties Electrical stimulation vagal nerve or anterior thalamus, palliative if AEDs or surgery is inadequate |
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Overall principles of tx of epilepsy
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seizure freedom (at least reduce frequency as much as possible, since szs beget szs, and szs can create brain lesions)
no adverse effects improve QOL convenient dosing regimens minimize cost |
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Older AEDs
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bromides
phenobarbital phenytoin ethosuximide carbamazepine valproic acid divalproex |
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Generic
Felbamate |
Brand
felbatol |
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gabapentin
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neurontin
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lamotrigine
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lamictal
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topiramate
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topamax
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tiagabine
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gabitril
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zonisamide
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zonegran
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oxcarbamazepine
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trileptal
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leveracetam
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keppra
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lacosamide
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vimpat
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rufinamide
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banzel
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vigabatrin
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sabril
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retigabin
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potiga
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eslicarbazepine
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stedesa
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