Antiepileptic Drugs Flashcards
(30 cards)
What is the goal of antiepileptic therapy?
To reduce the frequency and intensity of seizures; they are most effective at treating epileptic seizures.
What are the other indications of antiepileptic drugs?
Neuropathic pain; mood stabilization; migraine headache.
What is a seizure?
An excess of neuronal excitation (depolarization); the outcome depends on the location and focus of the activity.
How do AEDs impede the transmission of neuronal impulses?
(1) Sodium-channel blockade; (2) calcium-channel blockade; (3) glutamate (excitatory) antagonism; (4) GABA (inhibitory) enhancement.
How are AEDs typically used?
They are often used in combination to treat a specific type of seizure disorder; drugs used in combination are always chsen from different classes.
Describe the absorption of AEDs:
They undergo complete absorption; absorption is slowed by the presence of food in the stomach; absorption usually takes several hours (important when ordering labs).
Which drug is an exception in terms of absorption?
Gabapentin – it is absorbed via an amino acid transporter; high-protein meals will limit the absorption of Gabapentin.
Describe the auto-induction property of carbamazepine:
Carbemazepine is an auto-inducer (it stimulates its own metabolism); auto-induction dissipates in 3-4 weeks.
How is lamotrigine metabolized?
Phase II (glucuronidation).
How is valproic acid metabolized?
Through a combination of phase I and phase II.
What are the principle phase I enzymes involved with AEDs?
CYP2C19, 2C19, and 3A4; this is the source of many drug interactions, and the narrow therapeutic index of these drugs.
How do you characterize the phase I interactions of the older AEDs?
They tend to be CYP-450 inducers; this increases metabolism through the system, and decreases blood levels of other drugs.
How do you characterize the phase I interactions of phenytoin and carbamazepine?
They are broad-spectrum inducers; must monitor closely for DDIs.
How do you characterize the phase I interactions of newer AEDs (oxcarbazepine/topiramate)?
Thy tend to be a bit cleaner, but still induce the 3A4 system at higher doses.
How do you characterize the metabolic interactions of valproic acid?
It inhibits phase II metabolism, and is a 2C19 inhibitor.
Describe the therapeutic index of AEDs:
Older AEDs have a narrow TI (phenytoin/carbamazepine); the newer AEDs have a much wider TI; but data is less established for newer drugs.
When are AED serum concentrations useful, and when should labs be drawn?
They are useful fr optimizing therapy, monitoring adherence, or looking for possible DDIs; labs should be drawn after 4-5 half-lives have elapsed.
What is the caveat with newer AEDs?
Many of them are lousy AEDs in monotherapy.
How is AED metabolism altered in geriatrics?
Decreased albumin (higher free-drug); decreased hepatic enzymes; decreased renal clearance.
How is AED metabolism altered in children?
Metabolism is faster; may require higher, more frequent dosing.
Describe the use of AEDs during pregnancy:
Most are teratogenic; if they are used it will require higher, more frequent dosing.
How is AED metabolism altered in febrile illness?
Metabolism increases; AED serum levels are decreased.
How is AED metabolism altered in chronic renal disease?
Altered protein binding to albumin results in higher free drug; the patient will appear toxic at therapeutic levels (seen most often with valproic acid).
What is a concern when using AEDs with OCP therapy?
AEDs are 3A4 inducers, they decrease the efficacy of OCPs – this is especially concerning because AEDs are teratogenic.
