Antiseizure Drugs Flashcards
What are the two general types of seizures?
- Focal / partial
2. Generalized
What is a simple vs complex partial seizure?
Simple - consciousness is preserved, but one symptom manifests as a result of where the focal seizure is occurring
Complex - impaired consciousness which is associated with psychologic symptoms around the time of seizure occurrence
What are the two phases of “grand mal” seizures?
Generalized tonic-clonic
Tonic - abrupt loss of consciousness with increased muscle rigidity (tone)
Clonic - Jerking of body muscles with possible lip / tongue biting and fecal / urinary incontinence
What is “petite mal”?
Absence seizures, a form of generalized seizures, which generally last 10-20 seconds and cease by age 20. Can be present with automatisms, often causing impaired consciousness
3 Hz spike and wave on EEG
What is status epilepticus?
A series of usually tonic-clonic seizures without recovery of consciousness in between, a life threatening emergency
What are the risk factors for seizures in the elderly? Adults?
Alzheimers and stroke
In adults: trauma and tumors
What is the nature of current drugs in treatment of epilepsy in terms of their effectiveness?
They are anti-seizure, non anti-epileptogenic (simply raise the threshold for triggering a seizure, but do not decrease underlying electrical activity overexcitability of brain)
Why are the broad spectrum anti-epileptics generally good at suppressing seizures?
They prolong the inactivation of voltage-gated Na+ channels, which leads to increase suppression of areas with overactivity (rate-dependent)
How do drugs against absence seizures work?
Target the T-type Calcium channel which is important in thalamic neurons, which are the origin of absence seizures
What does a broader spectrum of activity of antiepileptic medication generally mean?
It has multiple mechanisms of action
What is the mechanism of action of carbamazepine and what seizures is it good for treating? Not good?
Prolongs the at Na channel inactivation - narrow spectrum
Good for the treatment of focal and generalized tonic-clonic seizures
Exacerbates absence seizures and myoclonic seizures -> do not use
What are the two primary indications for carbamazepine?
Trigeminal neuralgia and bipolar disorder
What is one broad spectrum AED which is also effective in the treatment of depression epileptic patients and bipolar disorder maintenance?
Lamotrigine - think of the llama
What is the mechanism of action and primary adverse effect of lamotrigine?
Blockade of Na channels (peanuts next to llama) as well as Ca+2 channels (considered broad spectrum)
Adverse: ataxia / diplopia (think of crossed eyes of camel) - same as CBZ
Why might lamotrigine be used over carbamazepine?
It does not induce or inhibit CYP450s. Carbamazepine is a potent auto-inducer of CYP3A4
What are the most common and most severe toxicities of carbamazepine? what should be done to limit toxicity?
Most common: Ataxia (pancake stack falling) and diplopia (crossed headlights of car)
Most severe - Steven-Johnsons syndrome - predicted by presence of a certain HLA-B allele most often seen in Asian patients
Screen for this allele and give with divided doses
What a final broad spectrum AED which can be used against all seizures? What is its mechanism of action?
Levetiracetam (think elevator)
Mechanism of action - binds SV2A glycoprotein in synaptic vesicles, modifying neurotransmitter release
What are the common adverse effects of levetiracetam and why is it used over the others?
Other than the typical ataxia and diplopia: causes somnolence
Used over the others for its clean PK profile - secreted unchanged by the kidney or nonhepatic metabolism to inactive metabolite (does not interact with CYP450).
