Flashcards in Antiseizure Drugs Deck (46):
What are the two general types of seizures?
1. Focal / partial
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?
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).
What drug is broad spectrum against all seizures and was accidentally discovered? Its mechanism of action?
Solvent dipropylacetic acid -> Valproic acid
Holds Na channels in the inactivated state, also augments GABA (Think of GABA CABA from sketchy -> at the festiVAL)
How does valproic acid modify gene expression?
It inhibits histone deacetylation
Why do we think valproate might be good against calcium channels?
Effective against absence seizures as well (tends to be reliant on T-type Ca+2 channels)
What are the main side effects of concern of valproic acid?
Mostly GI side effects - emperor vomiting in sketchy
Has been known to cause severe hepatotoxicity, especially in children -> requires liver function monitoring
What anticonvulsants should definitely not be used in pregnancy? What should be done if you need to continue them?
Valproic acid and carbamazepine - both cause neural tube defects
If continuation is needed: Give folate + lowest effective dose
What alternative sedative primarily maintains usage only in infants?
Phenobarbital - a barbiturate
What is a very old nonsedative AED which is rarely given in the US now but is still one of the most widely used drugs in the world?
Phenytoin (think of classic "tow" truck from sketchy)
What is the mechanism of action of phenytoin and how is it eliminated?
Think of chip bags with clips on the ground -> Na + channel blockade. Elimination is by liver and zero-order at high concentrations
What drug is primarily used for neuropathic pain and postherpetic neuralgia, and its mechanism of action?
Gabapentin - grab a pint!
Binds to voltage gated Ca+2 channel -> calciyumm ice cream truck
What are some of the other on-label and offlabel uses of gabapentin?
Onlabel - migraine, restless leg syndrome, refractory cough
Offlabel - CNS disorders, such as anxiety
What is one broad spectrum anticonvulsant most commonly used for offlabel treatment of refractory migraine and bipolar disorder? How does it work?
Topiramate! - Toupee -rimate from sketchy
Works by inactivation of Na+ , agonism to GABA-A allosteric site, and inhibition of carbonic anhydrase
What is the first line drug against absence seizures, and its mechanism?
Ethosuximide - think of Ethos from sketchy
Inhibits T-type Ca+2 channel (closed bottle of calciyumm next to this T-type Thermos)
What is the primary side effect of ethosuximide? When would you want to use the second line drug and what is it?
Dose-related GI stress
Second line drug: Valproic acid -> used when they may also have generalized seizures of different types, or focal seizures (ethosuximide only good for absence)
What benzodiazepine is good against absence seizures, and why is it not used?
Clonazepam, not used because of sedation, tolerance, and withdrawal
What other AEDs can be used against absence seizures?
Lamotrigine and levetiracetam
What is the standard treatment of status epilepticus? What should you watch for?
IV diazepam or lorazepam to stop the seizures, followed by IV phenytoin or phenobarbital
-> Watch for too much CNS depression
What benzo might be good to give in an ambulence for status epilepticus and why?
IM midazolam -> IM injection easier to give than IV lorazepam
What is the definition of seizure remission, and what percent can be withdrawn? What are the favorable factors for this?
>5 years seizure free, 75% can be sucessfully tapered and withdrawn
Favorable factors: low dose single medication users, with normal EEG
What antiseizure drugs are most difficult to get off of?
Benzodiazepines and barbiturates
What is Lennox-Gastaut syndrome and what is the best treatment?
Multiple seizures of different types, coupled with some mental disability.
Best treatment is ketogenic diet -> high fat, low carb, medium protein.
Secondary treatments include lamotrigine, levetiracetam, and valproate
How does a ketogenic diet work and what is it good for?
Leads to ketones being used as the primary source of brain fuel, rather than glucose.
Good for all seizure types, as starvation state (strict adherence required) will result in generalized less excitability of brain, and fewer seizures.
When is vagus nerve stimulation used and how does it work?
Works in drug-refractory seizure syndromes, with good response in most subjects. Mechanism is unclear, also works in depression and anxiety
What is RNS and how does it work?
Response neurostimulator device - electrical stimulation in brain foci for drug-refractory seizures -> works about as well as vagal stimulation
What is the most aggressive partial seizure treatment of adults which leaves most people seizure free for 5+ years?
Anterior temporal lobectomy
What can be done to prevent spread of seizures in Lennox-Gastaut syndrome?
What is the treatment for Rasmussen (encephalitis-type) or Sturge-Weber (port-wine vascularity spots) syndromes which cause severe epilepsy?
What are future pharmacologic targets for epilepsy therapy?
1. AMPA receptor antagonism
2. K+ channel activation