92b/93b - Epilepsy and Anticonvulsants Flashcards
Which 1st generation AEDs are enzyme inducers?
- Phenobarbital
- Phenytoin
- Carbamazepine
Which AED is the drug of choice for abscence seizures?
Ethosuximide
What is the mechanism of the benzodiazepines?
Which seizures do they treat?
Increased frequency of Cl- channel opening
Effective for myoclonic seizures
Rescue medication for status epilepticus
Describe the general mechanisms of seizure generation
- Too much excitation
- Ionic: too much inward Na+, Ca2+
- NeuroT: Too much glutamate, aspartate
- Too little inhibition
- Ionic: too little inward Cl-, outward K+
- NeuroT: Not enough GABA
What is the mechanism of ethosuximide?
What is it used for?
Blocks T-type Ca2+ currents in the thalamus
Drug of choice for abscence seizures
What is the most concerning possible side effect of lamotrigine?
Steven-Johnson syndrome
- But broadly, lamotrigine is a good broad-spectrum AED that is safe in pregnancy
Which AED can also be used for migraine prophylaxis and neuropathic pain?
Topiramate
Describe the signs of a myoclonic seizure
Myoclonic = generalized
- Myoclonus
- Brief, shock-like jerk of a muscle or group of muscles
- Bilateral, synchronous
- vs. clonus which is repeated rhythmic jerking
- If several myoclonic jerks occur in rhythmic succession, it is a clonic seizure
- Consciousness NOT impaired
Which AEDs are safe in pregnancy?
Lamotrigine
But need frequent adjustment in dose b/c serum levels fall in the 3rd trimester
Describe the signs of a tonic seizure
Tonic = generalized
- Symmetric, tonic muscle contraction of extremities
- Tonic flexion of waist and neck
- Lasts 2-20 seconds
- EEG
- Sudden attenuation, generalized polyspike waves
- (similar to atonic)
Which kind of epilepsy is characterized by focal seizures with impaired consciousness with automatisms?
Temporal lobe epilepsy
- Automatisms = lip smacking, swallowing, fumbling, picking at clothes
What is the mechanism of Levetiracetam?
What is it used for?
What is its notable side effect?
- Mechanism
- Binds to synaptic vescicle protein SV2A to regulate neurotransmitter release
- Also reduces activity through high-voltage Ca2+ channels
- Use
- Broad spectrum - used as monotherapy or adjunctive
- Side effect
- CNS depression and irritability
What EEG changes are associated with abscence seizures?
3 Hz spike-wave discharges in every channel
Lasts for 3-10 seconds
- Abscence seizures are generalized
- Sudden onset, sudden resolution
- No post-ictal confusion
What is the mechanism of carbamazepine?
What is it used for?
Inhibits Na+ channels
Tricyclic
Used to treat epilepsy w/predominantly focal seizures
Will worsen abscence seizures
Which kind of epilepsy is characterized by seizures that originate in the hippocampus and/or amygdala?
Mesial temporal lobe epilepsy
- Focal seizures evolve into a bilateral, convulsive seizure early on
In which populations should valproate be avoided?
- Pregnant women
- High risk of neural tube defects
- Neonates
- Hepatic toxicity due to elevated liver enzymes
Which AEDs can be used for neuropathic pain?
Gabapentin
Carbamazepine
Pregabalin
Which 1st generation AED is an enzyme inhibitor?
Valproate
What is the mechanism of zonisamide?
What is it used for?
Blocks Na+ and T-type Ca2+ channels
Blocks carbonic anhydrase (-> side effect = kidney stones)
Used as add-on therapy for partial and generalized seizures
What is the mechanism of gabapentin?
What is it used for?
Interferes with GABA uptake
Add-on therapy for focal seizures
Lacks potency for seizure - used off-label for neuropathic pain
Which AED is first line for generalized epilepsies?
What is its mechanism?
Valproate
- Broad spectrum
- Mechanisms:
- Enhances GABA activity
- Inhibits Na+ current
- Activates K+, T-type Ca2+ channels
Which AED causes significant appetite increase and weight gain?
Pregabalin
What is the mechanism of topiramate?
What is it used for?
What are the major side effects?
- Mechanism
- Blocks Na+ channels
- Increases frequency of GABAA opening
- Interferes with glutamate binding
- Uses
- Broad specturm (monotherapy or adjunctive for focal or general)
- Also used for migraine prophylaxis, neuropathic pain, tremor
- Side effects
- Memory and cognitive impairment
- Appetitie suppression and weight loss
List the 5 types of generalized seizures
- Atonic
- Tonic
- Clonic
- Tonic-clonic
- Tonic-clonic or myoclonic
- Abscence
Which AED induces its own metabolism? What is the significance?
Carbamazepine
Need to start at low doses and titrate up (will be inefective if the dose isn’t increased!)
What is the mechanism of pregabalin?
What is it used for?
What is its major side effect?
- Mechanism
- Inhibits voltage-gated Ca2+ channels
- Also reduces the release of some neurotransmitters
- Uses
- Neuropathic pain
- Peripheral neuropathy
- Fibromyalgia
- Anxiety
- Side effect
- Appetite increase and weight gain
Which AEDs can be used to treat migraine?
Valproate
Topiramate
Zonisamide
Which AED is likely to cause prominent hyponatremia?
Oxcarbazepine
What is the difference between a focal and generalized seizure?
Where the seizure starts
- Focal
- Seizure starts from one side
- May progress to affect both sides of the brain, resulting in motor activity on both sides of the body (a secondarily generalized seizure)
- Generalized
- Seizure start from both sides
Which AEDs can be used to treat bipolar disorder?
Lamotrigine
Valproate
Carbamazepine
What is the major difference between a focal seizure wtih impairment of consciousness and an abscence seizure?
No post-ictal confusion with abscence seizure
What defines epilepsy?
Recurrent (2+) seizures that are not provoked by systemic or acute neurological insults
- This excludes seizures due to metabolic disorders or alcohol or sedative drug withdrawal or
What is the mechanism of phenytoin?
What is it used for?
Inhibits rapid firing of Na+ channels
Phenytoin is the most widely used AED
Used extensively to treat status epilepticus
Which kind of epilepsy is characterized by seizures preceded by aura?
Temporal lobe epilepsy
- Aura may involve epigastric sensation, deja vu, emotional feeling, perceptual distorion, autonomic
Which AED does not have complete absorption >4mg?
Gabapentin
Describe the signs of an atonic seizure
Atonic = generalized
- Sudden loss of postural tone
- Severe = fall
- Mild = head or jaw draw
- Consciousness usually impaired
- EEG
- Sudden diffuse atenuation, generalized polyspike waves
- Similar to tonic
Which AED is likely to cause a drop in IQ during therapy, memory deficits, appetite suppression, and weight loss?
Topiramate
What is the mechanism of oxcarbazepine?
What is it used for?
Blocks Na+ channels
(its basically better carbamazepine; less risk of toxic metabolite buildup)
Used for monotherapy in focal (aka partial) seizures
Note: tends to cause prominent hyponatremia
Describe the signs of a tonic-clonic seizure
Tonic-clonic = generalized
- Loss of consciousness
- Post-ictal confusion, lethargy
- Tonic phase
- Stiffening + fall
- Ictal cry
- Clonic phase
- Rhythmic extremity jerking
- Drooling, foaming at the mouth, biting tongue
- Bladder and bowel incontinence
- Agitation
Describe the signs of an abscence seizure
Abscence = generalized
- Sudden onset
- Eye blinks
- Brief automatic mouth or hand movments
- Changes in muscle tone
- No post-ictal confusion
Which AED is associated with aplastic anemia and hepatic failure?
Felbamate
Which AED is most likely to cause CNS depression and irritability?
Levetiracetam
What is the mechanism of phenobarbital?
Increases duration of GABAA Cl- channel opening
Side effect: may cause CNS depression when combined with alcohol or benzos
What is the mechanism of lamotrigine?
What is it used for?
Inhibits Na+ channels and glutamate release
- Broad spectrum
- Monotherapy or or adjunctive for generalized and focal seizures
- Safe in pregnancy!!
- But serum levels fall in 3rd trimester, needs adjustment
Feared side effect = Steven-Johnson syndrome
Which kind of seizure is associated wtih generalized 3 Hz spike-wave discharges on EEG?
Abscence
Describe the seizures commonly associated with temporal lobe epilepsy
- Preceded by aura
- Often a weird taste in the mouth
-
Focal seizures with impaired consciousness with automatisms
- Lip smacking, swallowing, fumbling, picking at clothes
Often cannot be medically controlled; opt for anteromesial temporal lobectomy
Which two “clinically relevant” drugs may exacerbate epileptic seizures?
Tramadol (an analgesic)
Venlafaxine (an SNRI antidepressant)
