AEDs Flashcards
Pregabalin:
- Mechanism of action
- Bioavailability
- Hepatic metabolism?
- Excretion
Pregabalin
- Mechanism of action: structural analog of Gaba, binds to alpha-2-deta subunit of voltage-gated calcium channel
- Bioavailability drops from 60%-33% when total daily dose increased form 900 to 3500 mg
- Not hepatically metabolized
>90% excreted unchanged in urine
Drugs to avoid in:
- Dravet Syndrome
Sodium channel agents (may worsen)
Primary side effects to consider: Phenobarbital (6)
- sedation
- rash
- hepatotoxicity
- aplastic anemia
- osteopenia
- CT d/o
Primary side effects to consider:
Phenytoin
General (6)
Dose dependent (5)
- SJS
- Blood dyscrasia
- hepatotoxicity
- gingival hyperplasia
- hirsutism
- osteopenia
Dose-dependent - Nystagmus
- Diplopia
- ataxia / incoordination
- dysarthria
- Drowsiness
Primary side effects to consider:
Primidone
Same as phenobarbital (metabolized into phenobarbital)
Primary side effects to consider:
Ethosuximide
stomach upset
abdominal pain/cramps
Primary side effects to consider: clonazepam (4)
- somnolence
- lethargy
- sexual dysfunction
- tolerance (long term)
Primary side effects to consider:
Clorazepate (tranxene)
- Somnolence
- Lethargy
Primary side effects to consider:
Carbamazepine (8)
- Sedation
- Neutropenia
- hyponatremia
- bradycardia
- SJS
- Agranulocytosis
- Hepatotoxicity
- pancreatitis
Primary side effects to consider:
Valproate (7)
- Weight gain
- tremor
- thrombocytopenia
- pancreatitis
- hepatotoxicity
- hyperammonemia
- Hair loss
Primary side effects to consider:
VIgabatrin (3)
- permanent visual field deficit (older studies say 30-40%, likely less)
- reversible subcortical edema
- somnolence
Primary side effects to consider:
Zonisamide (5)
- Cross-reacts with sulfa
- hypohydrosis
- nephrolithiasis
- metabolic acidosis
- weight loss
Primary side effects to consider:
Lamotrigine (4)
- NON-sedating
- insomnia
- SJS
- myoclonus
Primary side effects to consider: Felbamate (3 + 4)
- aplastic anemia
- liver failure
- weight loss
- Increases levels of phenytoin, valproate, phenobarbital, clobazam
Primary side effects to consider:
Gabapentin (3)
- sedation
- weight gain
- myoclonus
Primary side effects to consider:
Topiramate (5)
- weight loss
- cognitive slowing
- dysesthesia
- Glaucoma
- nephrolithiasis
Primary side effects to consider:
Tiagabine (3)
- Sedation
- cognitive slowing
- worsens some generalized seizures (myoclonic, absence)
Primary side effects to consider:
Oxcarbazepine (4)
- hyponatremia (per book only in elderly)
- Decreases OCP levels
- Sedation
- Rash
Primary side effects to consider:
Levetiracetam (2)
- Irritability
- Depression
Primary side effects to consider: pregabalin (3)
- Sedation
- swelling in lower extremities
- blurred vision
Primary side effects to consider:
Rufinamide (3)
- Loss of apetite
- aggravated seizures
- Status epilepticus
Primary side effects to consider:
Lacosamide (7)
- Dizziness / vertigo > vomiting
- Ataxia
- diplopia
- Blurred vision
- Fatigue
- Rash
Primary side effects to consider:
Esclicarbazepine (aptiom) (4)
- Nausea
- Dizziness
- Diplopia
- hyponatremia (1-2%)
Primary side effects to consider:
Clobazam (3)
- somnolence
- lethargy
- note less addictive potential than other benzo
Primary side effects to consider:
Ezogabine (potiga) (3)
- Urinary Retention
- Tremor
- bluish skin discoloration
Primary side effects to consider:
Perampanel (fycompa)
- Ataxia
- Severe mood issues (hostility, homicidal ideation, aggression)
ASM’s to Consider:
Focal onset, +/- secondary generalization
- Main (5)
- Less preferred (4)
Main:
- Lamotrigine
- levetiracetam
- oxcarbazepine
- lacosamide
- topiramate
Less likely as 1st agent:
- Carbamazepine
- Valproate
- Esclicarobazapine
- phenytoin
ASM’s to Consider:
Primary GTC (5)
- Valproate
- Levetiracetam
- Lamotrigine
- Topiramate
- zonisamide
ASM’s to Consider:
Absence (3)
Drugs to avoid: (5)
Consider
- Ethosuximide
- Valproate
- (less preferred) lamotrigine
AVOID
- phenytoin
- carbamazepine
- gabapentin
- tiagabine
- vigabatrin
ASM’s to Consider:
Generalized myoclonic (3)
Drugs to avoid (6)
Consider
- levetiracetam
- valproate
- clonazepam
Avoid
- phenytoin
- carbamazepine
- gabapentin
- tiagabine
- vigabatrin
- pregabalin
ASM’s to Consider
SeLECTS (2)
- LEV
- OXC
ASM’s to Consider:
young women (3)
Avoid (1 + 2 others)
Consider
- levetiracetam
- lamotrigine
- lacosamide
Avoid
- Valproate (teratogen)
- Carbamazepine
- Phenytoin
ASM’s to Consider:
Depressed patient (1)
Avoid (3)
Consider
- Lamotrigine
Avoid
- pheyntoin
- phenonbarbital
- primidone
ASM’s to consider:
Emotionally labile person (5)
Avoid (1)
Consider (due to mood stabilizing effect)
- Valproate
- carbamazepine
- lamotrigine
- oxcarbazepine
- topiramate
Avoid
- Levetiracetam
ASM’s to Consider:
Hepatic disease (3)
Avoid (3)
Consider:
- Levetiracetam
- lamotrigine
- pregabalin
Avoid
- valproate
- phenytoin
- carbamazepine
ASM’s to Consider:
obesity (2)
avoid (3)
Consider (due to weight loss)
- Topiramate
- Zonisamide
Avoid
- Valproate
- Gabapentin
- Pregabalin
ASM’s to Consider:
Chronic pain (4)
- Gabapentin
- pregabalin
- carbamazepine
- pregabalin
ASM’s to Consider:
on many other meds (3)
Avoid (1)
Consider
- Levetiracetam
- pregabalin
- gabapentin
Avoid
Enzyme inducers
ASM’s to Consider:
Han Chinese or Taiwanese
Carbamazepine
oxcarbazepine
Note: can use if you check HLA-B 1502)
Patient on ASM develops rash, what cross-reactivities do you need to consider (4)
Carbamazepine <>Oxcarbazepine
Carbamazepine <>Phenytoin
Carbamazepine <>Phenobarbital
Phenytoin <>Zonisamide
Enzyme Inducing ASMs:
strong (5)
Weak (1)
Strong
- Phenobarbital
- primidone
- phenytoin
- carbamazepine
- Oxcarbazepine (doses >900 mg)
Weak
- Lamotrigine (weak)
Enzyme inhibiting ASM
Strong (1)
Weak (1)
Strong: Valproate
Weak: Topiramate
Phenobarbital lowers concentrations of which ASM (3 main + 1), and what 3 other non-asm drugs
- valproate
- ethosuximide
- lamotrigine
- may reduce carbamazepine, but increase carbamazepine epoxide
Also reduces effectiveness of - warfarin
- steroids
- OCP
Patient with epilepsy and Dupuytren’s Contracture.
- What medicine could they be on that could cause this?
- What other connective tissue conditions is this med also associated with?
Phenobarbital
Also associated with
- platar fibromatosis
- frozen shoulder
Pregnancy risk: Phenobarbital
Category
Risks (2)
Category:
- D
Risks:
- cardiac malformations
- reduced cognitive abilities (in male offspring)
Pharmacokinetics: phenytoin
oral bioavailability: adults
oral bioavailability: Neonates
Factors that reduce oral bioavailability (3)
Oral Bioavailability: adults - 90%
oral bioavailability: neonates - much lower
Also reduced with
- Nasogastric feedings
- calcium
- antacids
Patient in ICU for breakthrough seizures treated with fosphenytoin has toxicity at an unexpectedly low dose. What medication could they be on and why did this happen?
Valproate - competes for protein binding sites, which leads to higher Free levels of phenytoin
ASM metabolization,Carbamazepine:
- Non-ASMs that can affect concentrations (4)
- Metabolite affected by what 4 ASM
Affects concentration d/t CYP3A4
- Macrolide antibiotics (other than azithromycin)
- Fluoxetine
- Propoxyphene
- Grapefruit juice
Metabolite (epoxide) affected by
- valproate
- felbamate
- oxcarbazepine
- zonisamide
ASM metabolization, Carbamazepine:
- Important factor about dosing
-What 4 drugs do you need to be especially notable for and why?
Dosing:
- Auto-inducer (takes 2-4 weeks to reach steady state)
Strong inducer of cytochrome P450, increases clearance of:
- OCPs
- Warfarin
- Valproate
- lamotrigine
Oxcarbazpine:
- Bioavailability
- half-life (main drug)
- half-life (active metabolite)
- Big reasons why it replaced carbamazepine (2)
- bioavaibility- 90%
- half-life (main drug) 1-3.7h
- half-life (metabolite) 8-10 h
Replaced carbamazepine due to - Not affected by 3A4 inhibitors (fluoxetine, erythromycin, grapefruit juice)
- No auto-induction
What condition is Felbamate approved by the FDA to treat specifically?
Lennox-Gastaut Syndrome
Patient with Absence seizures presents with fever, arthralgia, malar rash?
- What two should you get?
- What two organs can also be involved
- What other two ASMs can cause this
Lupus-like syndrome (Ethosuximide, Phenytoin, Carbamazepine)
Labs:
- Elevated ANA
- Elevated anti DS DNA antibodies
Other organ systems
- Pleural effusion
- Myocarditis
Why does topirimate cause kidney stones?
inhibits carbonic anydrase
- Increased urinary citrate
- Alkalinized urine
risk factors for aplastic anemia when starting felbamate (6)
- female sex
- caucasian race
- Adult age
- history of cyotopenia
- allergy / toxiticy to other ASM
- diagnosis / serological evidence of an autoimmune disorder
Mechanism of action: felbamate
binds to NR2B subunit of NMDA receptor (selective inhibition)
factors that increase risk of VPA-induced hyperammonemia (6)
- urea cycle defects
- carnitine deficiency
- protein rich diets
- hypercatabolic states
- phenobarbital
- topiramate
Why does levocarnitine help with VPA-induced hyperammonemia?
- Carnitine required for beta-oxidation
- VPA depletes carnitine
- this shifts to OMEGA-oxidation > toxic metabolites > ammonia
Which other AED, when taken with VPA, can increase risk of valproate-induced encephalopathy?
Why?
- Topiramate
- synergistic action on Ornithine metabolism > hyperammonemia
medication known to case spike-wave-stupor
Tiagabine (either for seizures or insomnia)
Side effects of AcTH
- Leading causes of death (2)
- Other symptoms (4)
- MRI findings (onset, peak, resolution)
Leading causes of death:
- cardiomyopathy
- infection
others:
- hypertension
- proteinuria
- bleeding
- neuropsych (agitation, apathy, insomnia)
MRI:
- onset: within first week
-maximum 4 weeks
- resolves 1-4 weeks following completion of treatment
mechanism of action: Esogabine
potassium channel opener
Name two differences between visual changes that happen with Vigabatrin versus Esogabine
1: cause
- Ezogabine: due to pigmentary abnormalities
- Vigabatrin: damage to the nerve
2: Reversibility
- Ezogabine: reversible
- Vigabatrin: Irreversible
HLA alleles and what they’re associated with:
HLA-B1502 (2)
HLA-A3101 (2)
HLA-B1502: CBZ-induced Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
HLA-A3101: CBZ_induced Hypersensitivity syndrome (HSS) and Maculopapular exanthema (MPE)
Felbamate drug interaction:
What enzyme?
What ASMs can increase (2)
What ASMs can decrease (1)
Enzyme: CYP2C19
Increases:
- phenytoin
- valproate (but due to metabolism by beta-oxidation)
Decreases:
- carbamazepine (and epoxide)
