seizure drugs Flashcards
What types of seizures are narrow spectrum seizure drugs good for? Broad spectrum?
narrow spectrum are effective against partial seizures, including secondarily generalized seizures
broad spectrum are effective against both partial and generalized seizures
What are the narrow spectrum seizure drugs? Broad spectrum?
narrow: carbamazepine, phenytoin, phenobarbital, gabapentin, tiagabine
broad: valproate, topiramate, lamotrigine, clonazepam
What is the only indication for ethosuximide? What is the only indication for lorazepam?
ethosuximide - absence seizures
lorazepam - status epilepticus
What anti-epileptic drugs predominantly act by inhibiting voltage gated Na+ channels by stabilizing the inactivated state of the channel?
phenytoin, carbamazepine, valproate, topiramate, lamotrigine
What anti-epileptic drugs predominantly act by enhancing GABA-A receptors activity? By increasing synaptic levels of GABA?
Positive allosteric effect on GABA receptor: the benzodiazepines, phenobarbital, topiramate
Increasing synaptic levels of GABA: tiagabine, gabapentin (maybe)
What channels are defective in absence seizures? What are the AEDs used against absence seizures?
T-type Ca2+ channels that allow excessive current through them lead to absence seizures.
Effective drugs against absence seizures are: ethosuximide, valproate, clonazepam
What AED’s mechanism of action is to inhibit the N/P type Ca2+ channels that mediate neurotransmitter release?
lamotrigine
What AED’s mechanism of action is to modulate AMPA glutamate receptors?
topiramate
What AED’s mechanism of action is to inhibit carbonic anhydrase?
topiramate
What AED’s mechanism of action is to enhance conductance of K+ channels?
valproate
What are the initial treatment options for status epilepticus? What should you give if the patient the seizure is refractory to initial treatments?
Initial: benzodiazapenes (lorazepam and diazepam) and fosphenytoin/phenytoin
If refractory: add phenobarbital or valproate
If seizures not controlled after 1 hour, induce general anesthesia
In pharmacokinetic theory, what is induction? What is competition?
induction - when drug A increases the gene expression of an enzyme (usually a P450) that breaks down drug B so that drug B is eliminated faster
competition - when drug A and B are broken down by the same enzyme but drug A has a higher affinity so that the rate of elimination for drug B is slowed
What enzyme are almost all AED inducers of? What are the implications of this?
All of the older AEDs, phenytoin, carbamazepine, phenobarbital, (and the newer AEDs to a lesser extent) induce cytochrome P450 3A4 and many other P450s.
Since half of all drugs are metabolized by 3A4, drug interactions with AEDs are very common and need to be considered if treating with an AED
What happens to the metabolism of valproate and lamotrigine when they are given together?
Valproate competes with lamotrigine for a phase II enzyme, resulting in increased levels of lamotrigine because the body cannot eliminate it
What AEDs are most likely to cause birth defects/teratogen?
phenytoin, carbamazepine, phenobarbital, valproate
What AEDs are most likely to cause hypersensitivity reaction like Stevens-Johnson syndrome?
phenytoin, carbamazepine, phenobarbital, ethosoximide, lamotrigine
What AEDs are most likely to cause cognitive slowing?
phenytoin, carbamazepine, phenobarbital, valproate, topiramate
What AEDs are most likely to increase seizure activity or induce seizures?
phenytoin, tiagabine
What kind of kinetics does phenytoin exhibit?
Somewhere in-between zero order and first order kinetics. This means that increasing the dose will result in a disproportionally large increase in plasma concentration
The kinetics of phenytoin vary widely from person to person
Which AED is an inhibitor of CYP450s?
valproate
What are the adverse effects of ALL AEDs?
suicidal thoughts and behaviors
What are the adverse effects of phenytoin?
nystagmus and ataxia
megaloblastic anemia
hyperplastic gums
coarsening of facial features
What are the adverse effects of phenobarbital?
megaloblastic anemia
may produce paradoxical excitatory effect in children
potential for abuse
What are the adverse effects of valproate?
initially nausea, vomiting and anorexia but weight gain after chronic use tremor alopecia thrombocytopenia hepatotoxicity
What are the adverse effects of carbamazepine and ethosuximide?
dizziness, diplopia
N/V
leukopenia and agranulocytosis
What are the adverse effects of lamotrigine?
hypersensitivity reactions (e.g. Stevens-Johnson syndrome)
diplopia
Relatively free of adverse effects!
What are the adverse effects of gabapentin?
weight gain
Which AED has a completely renal elimination?
gabapentin
What are the adverse effects of benzodiazapenes?
weight gain
What AEDs are used for bipolar disorder?
valproate, carbamazepine and lamotrigine
What AEDs are used for neuropathic pain?
carbamazepine - trigeminal neuralgia
gabapentin - post-herpetic neuralgia
What AEDs are used for migraine prophylaxis?
topiramate, valproate
What AEDs are used for alcoholism?
topiramate
