AEDS Flashcards
What new AED is associated with aggression?
Perampanel
Does perampanel cause a dose dependent side effect of aggression?
Yes
What age is the most common for dose dependent aggression with perampanel use?
Adolescents it is about 7.8% and in adults 1.3%
What is the most common psychological side effect of perampanel?
Irritability, seen in 11.8%
What AEDs have been sown to be effective for JME?
LEV, VPA, TPM, CLB
What AED can aggravate seizures in JME?
LTG
What AEDs aggravate absence seizures?
CBZ, OXC, GBP, TGB
What are the neuropsychological effects of AEDs?
Slowing of psychomotor speed and vigilance, and this risk is increased with rapid titration, higher dose, and polytherapy.
Can AEDs effect IQ in aldolescents and adults?
No, when used in mono therapy
Can AEDs effect IQ in a fetus or young?
Yes
When does the risk for TPM for cognitive side effects increase?
Dosing above 200 mg/day
What AEDS have the lowest risk for congenital malformations?
CBZ, LTG, LEV, and OXC
Which HLA alleles are associated with highest risk for TEN and Stevens-Johnson?
HLA-B 1502 in Asians only.
What HLA allele is associated with hypersensitive syndrome and maculopapular rash?
HLA-A 3101 in a variety is ethnic groups
What drugs are mostly renal excreted?
Levetiracetam, gabapentin, and pregabalin
What is the usual metabolism types that can be induced or inhibited by other drugs?
Drugs that undergo oxidation or glucuronidation
What AEDs does not reduce the efficacy of oral contraceptive pills?
Valporic acid
What AEDs alter oral contraceptive efficacy?
PHE, CBZ, TPM, OXC induce the clearance of ethinyl estradiol and/or synthetic progestin
Congenital malformations are increased with what AEDs?
Valproic acid are dose dependent, and TPM
Is there a difference between LTG and CBZ in congenital malformations?
Registries have not shown differences between the two.
What is the study design for obtaining FDA approval for the use of AED as mono therapy?
Conversion to mono therapy superiority design.
What type of proof will the FDA accept for monotherapy?
Only proof of superiority over standard treatment.
What two AEDs can induce skin rash due to cross-reactivity?
PHE and CBZ
What is the percentage of patients who gat skin rash from AED exposure?
As high as 15%
What other AED has cross-reactivity to CBZ?
Phenobarbital, but less than PHT
How does St John’s Wort alter AED levels?
Induction of cytochrome P450 enzymes.
What compounds in herbal medications have the greatest interactions with medications?
Hypericum perforating, magnesium, calcium, iron or ginkgo
When are serum concentrations beneficial to obtain?
- Individual level where a problem achieves desired outcome.
- Aid in diagnosis of toxicity.
- Assessing adherence
- Guiding dose adjustments during situations associated with pharmacokinetic variability
5 . When a known pharmacokinetic change will happen- pregnancy - Guiding dose adjustments for AEDs with dose dependent pharmacokinetics- Dilantin
What is the most important factor in determining the clearance of Dilantin?
Variants of CYP 2C9 and 2C19 the strongest predictors of clearance
How is LTG metabolized?
Glucuronidation
During pregnancy which AED can have increased clearance by up-to 200%?
LTG
When during pregnancy does estrogen have it’s largest effect on clearance of LTG?
First trimester
When does clearance of LTG return to pre-pregnancy levels?h
Shortly after delivery
When should LTG be monitored during pregnancy?
Prior to pregnancy, shortly after conception, during each trimester, and shortly after delivery:
What drug significantlyj reduces CBZ?
Grapefruit juice
How does grapefruit juice lower CBZ levels?
Lowers absorption.
What common antibiotics that inhibit the metabolism of CBZ?
Amoxicillin and macrolides
What can be given after surgery that would elevate CBZ?
Dacron
How does vigabrin work?
Increasing GABA by GABA trans Amina’s inhibition
Does vigabatrin block type A type B GABA receptors?
No
How does Tiagabine work?
Blocking presynaptic reuptake of GABA
What is the mechanism of action of LEV?
Binding of synaptic vesicle protein SV2A
What are the signs of CBZ toxicity?
Ataxia, lethargy, dizziness, and nystagmus
What antibiotic class reduce clearance of CBZ by blocking metabolism?
Macrolides
What are the major side effects of eslicarbazepine?
Dizziness, somnolence, and headaches
What are minor side effects of eslicarbazepine?
Hyponatrmia and dermatologist
Does eslicarbazepine alter birth control pills?
Yes, lowers the levels
What is the major side effect of ezogabine?
Urinary retention
What is the mechanism of action of CBZ, PHE, LAC?
Modulation of the sodium channel
Hyponatremia is more likely in patients treated with CBZ or OXC?
OXC was found in 12% versus 3% for CBZ
What is the predictive finding hyponatremia with OXC?
The first measurement of sodium was found to be predictive
Which medications have class Level A evidence as initial therapy in CAE?
Valproic acid and ethosuximide
What AEDs have class Level A evidence for initial monotherapy for focal onset seizures?
LEV, ZNS, VPA, and CBZ
What is propofol infusion syndrome?
Severe metabolic acidosis, renal failure, cardiovascular collapse
What makes a patient particularly susceptible?
On the Ketogenic diet
What evidence exists for effectiveness for cannibidiol?
Anecdotal evidence
What is Type A adverse effects?
Common effects (>10%) that are related to known mechanism of action and dependent on dose or serum concentration.
What is the most common adverse reaction from drug treatment of status?
Hypotension
After hypotension, what is the next most common adverse reaction from drug treatment of status
Hypoventilation
What is required by the FDA for approval of generic AED?
Single dose study in volunteers
What AED is most likely to produce seizure suppression in super-refractory status?
Pentobarbital
What drug associated with treatment of super-refractatory status has the most systemic adverse effects?
Pentobarbital
How common is weight gain with VPA?
10% - 70%
What are the most common metabolic side effects of VPA?
Insulin resistance and hyperlipidemia
How frequent are congenital malformations in VPA exposure?
10%
What AEDs are poorly absorbed rectally?
Gabapentin, oxcarbazepine, lorazepam, and phenytoin
What AEDs are absorbed well when given rectally?
Topiramate, clonazepam, and levetiracetam
What is the most effective and best tolerated for treatment of CAE?
Ethosuximide
What cation chloride co-transporters are most important in adult neurons?
KCC2 which is responsible for low intracellular chloride concentrations. Then activation of GABA(A) receptors allows the entry of chloride and hyperpolarization and inhibition
In the infant what cation chloride transporter is dominant?
NKCC1 and this elevates the intracellular chloride levels. Thus when GABA(A) is activated it causes an outward movement of chloride leading to neuronal depolarization and excitation
In a patient already on VPA, what happens when CBZ is added?
Free VPA levels increase due to competition for protein binding sites
What drugs increase free VPA levels?
CBZ, phenytoin, and salicylate
Is there any clinical trial evidence for second line therapy for convulsive status?
No
Does Perampanel have a black box warning for behavioral reactions?
Yes, for hostility, aggression, but seems to beside related
What is the mechanism of action is eslicarbazepine?
Enhances slow inactivation of sodium channels. It might also inactivate calcium currents.
In pregnant women what AED is thought to be superior to LTG and TPM and similar to CBZ and VPA?
LEV
What factors are associated with VGB and visual effects?
Visual effects increased with duration of exposure and higher cumulative dosage
Which AEDs are associated with fewest cognitive side effects?
LTG, LEV LAC, GPB, VGB
What are the signs of lamotrigine toxicity?
Double vision, dizziness and ataxia
What AEDS do not interact with oral contraceptives?
GBP, LEV, ZNS
What non-intravenous medication has the best evidence for treating seizures lasting at least 5 minutes?
Intramuscular midazolam
What AEDs have been associated with spina bifida?
VPA and CBZ
What AEDs have no relevant metabolic drug-drug interactions?
GBP, LEV, Pregabalin