AED Prescription Flashcards
Typically NPs do not
prescribe AEDs for epilepsy and seizures in primary care
• Neurology initiated; primary care may monitor
• Potential use of BZDs in emergency situation
• Seizure free 0-12 months before allowed to drive*
Some AEDs can be prescribed to treat
migraine headache
• Topiramate
• Valproic Acid
Some AEDs are prescribed to treat
Mental Health conditions • Carbamazepine • Valproate • Lamotrigine • Topiramate • Gabapentin
Pharmacokinetic Factors
in the Elderly - AED
Absorption - little change
⬧ Distribution
• Decrease in lean body mass important for highly lipid-soluble drugs
• Fall in albumin leading to higher free fraction
⬧ Metabolism - decreased hepatic enzyme content and blood flow
⬧ Excretion - decreased renal clearance
Pharmacokinetic Factors
in Pediatrics - AED
⬧ Neonate - often lower per kg doses • Low protein binding • Low metabolic rate ⬧ Children - higher, more frequent doses • Faster metabolism
Pharmacokinetics in Pregnancy - AED
⬧ Increased volume of distribution ⬧ Lower serum albumin ⬧ Faster metabolism ⬧ Higher dose, but probably less than predicted by total level (measure free level) ⬧ Consider more frequent dosing ⬧ Return to pre-pregnancy conditions rapidly (within 2 weeks) after delivery
Be aware that drug interactions may occur when there is the:
- addition of a new medication when an inducer/inhibitor is present.
- addition of inducer/inhibitor to an existing medication regimen.
- removal of an inducer/inhibitor from chronic medication regimen.
AEDs and Drug Interactions
⬧ Although many AEDs can cause pharmacokinetic interactions, several agents appear to be less problematic. ⬧ AEDs that do not appear to be either inducers or inhibitors of the CYP system include: gabapentin lamotrigine pregabalin tiagabine levetiracetam zonisamide lacosamide
• Important note about oral contraceptives (OCPs):
• OCP efficacy is decreased by inducers, including: phenytoin, phenobarbital,
primidone, carbamazepine, and higher doses of topiramate and oxcarbazepine
• OCPs and pregnancy significantly decrease serum levels of lamotrigine.
Serum concentrations are useful when optimizing
AED therapy,
assessing adherence,or teasing out drug-drug interactions.
Serum concentations should be used to
They should be used to monitor pharmacodynamic and
pharmacokinetic interactions.
Serum concentrations should be done
⬧ Should be done when documenting a serum concentration when a
patient is well controlled.
Serum concentrations are also useful when
Serum concentrations are also useful when documenting positive or
negative outcomes associated with AED therapy.
Serum concentrations most often indvidual patients
Most often individual patients define their own “therapeutic range” for
AEDs.
Serum concentrations for the newAED there is no clearly
For the new AEDs there is no clearly defined “therapeutic range”.
Metabolic Changes of AEDs - Febrile
- ↑ metabolic rate and ↓ serum concentrations
* ↑ serum proteins that can bind AEDs and ↓ free levels of AED serum concentrations
Metabolic Changes of AEDs - Severe hepatic disease
- Impairs metabolism and ↑ serum levels of AEDs
- ↓ serum proteins and ↑ free levels of AED serum concentrations
- Often serum levels can be harder to predict in this situation
Metabolic Changes of AEDs - Renal
- ↓ the elimination of some AEDs
* gabapentin, pregabalin, levetiracetam
Metabolic Changes of AEDs - Chronic Renal
- ↑ protein loss and ↑ free fraction of highly protein bound AEDs
- It may be helpful to give smaller doses more frequently to ↓ adverse effects
- phenytoin, valproic acid, tiagabine, vigabatrin
Metabolic Changes of AEDs - Hemodialysis
⬧ Serum concentrations pre/post dialysis can be beneficial in this patient population
⬧ Bolus dosing of AEDs is sometimes recommended in this situation
Sedation, fatigue -
All AEDs, except unusual with LTG and FBM
− More pronounced with traditional AED
Unsteadiness, incoordination, dizziness
− Mainly traditional AEDs
− May be sign of toxicity with many AEDs
Tremor
VALPORIC ACID
Paresthesia
(topiramate, zonisamide)
Diplopia, blurred vision, visual distortion
(carbamazepine, lamotrigine)
Mental/motor slowing or impairment
(topiramate)
Mood or behavioral changes
(levetiracetam)
Changes in libido or sexual function
(carbamazepine,
phenytoin, phenobarbital)
Mild to moderate laboratory changes
- Hyponatremia: carbamazepine, oxcarbazepine
- Increases in ALT or AST
- Leukopenia
- Thrombocytopenia
Weight gain/appetite changes
- valproic acid
- gabapentin
- pregabalin
- vigabatrin
Weight loss
- topiramate
- zonisamide
- Felbamate
Hematologic damage
Marrow aplasia, agranulocytosis Early symptoms: abnormal bleeding, acute onset of fever, symptoms of anemia Laboratory monitoring probably not helpful in early detection Felbamate aplastic anemia approx. 1:5,000 treated patients Patient education
Endocrine/Metabolic Effects
Osteomalacia, osteoporosis (Vit D deficiency or other) • carbamazepine • barbiturates • phenytoin • oxcarbazepine • valproate
Teratogenesis (folate deficiency or other)
- barbiturates
- phenytoin
- carbamazepine
- valproate (neural tube defects)
- topiramate (cleft lip/cleft palate
Altered connective tissue metabolism or growth (facial
coarsening, hirsutism, gingival hyperplasia or contractures)
- phenytoin
* phenobarbital
Neurologic
- Neuropathy
- phenytoin
- carbamazepine
- Cerebellar degeneration
- phenytoin
Sexual Dysfunction (polycystic ovaries et al.)
- phenytoin
- carbamazepine
- phenobarbital
- primidone
AED Hypersensitivity Syndrome
⬧ Characterized by rash, systemic involvement
⬧ Arene oxide intermediates - aromatic ring
⬧ Lack of epoxide hydrolase
⬧ Cross-reactivity
• phenytoin
• carbamazepine
• Phenobarbital
• oxcarbazepine
⬧ Relative cross reactivity - lamotrigine
