Pharmacology Of Epilepsies And Seizures Flashcards
(36 cards)
Definition of a seizure
Episode of abnormal neuronal excitation and discharge in the CNS
Definition of status epilepticus
A seizure that lasts greater than 5 min or 2 seizures within 24 hrs
medical emergency
more acute
Definition of epilepsy
Recurrent seizures
prolonged activity can result in neuron death and damage
more chronic
Surface etiology of seizures
Is disruption off the balance in inhibitory and excitatory neurons
- CAN BE EITHER, bout its usually GABA inhibition and glutamate abundance.
Pharmacology Management is to:
- decrease activity of excitatory neurons
- increase activity of inhibitory neurons
How does surround inhibition work in the normal nervous system
GABAergic neurons surrounding the activated circuit are simultaneously activated when a 1st order neuron is excited
Allows for neurons outside of the designated circuit to be inhibited, funneling the signal through the proper circuit
- many structures have many nerves attached to each other to various pathways. It’s important for GABA neurons to be able to funnel a signal through a proper pathway
**loss of surround inhibition results in seizures (since multiple pathways are activated at once)
Classifications of seizures
1) Partial seizures = focal seizures
- Simple partial = focal aware
* no loss of consciousness
- Complex partial = focal impaired
* loss of consciousness
2) Grand mal = generalized tonic-clonic
3) Petit mal = generalized absence
4) Partial seizures that progress to grand mal = focal-to-bilateral tonic-clonic
Symptoms of a simple partial (focal aware seizure)
Involuntary repetitive movements
Paresthesia
Flashing lights
*consiousness is preserved
**all symptoms are ipsilateral
Symptoms of a complex partial (focal imparied) seizure
Abnormal activity of the temporal lobe
Involuntary repetitive movements (automatisms)
*consciousness is impaired
** very classically preceded by an aura
*** is ipsilateral
Symptoms of a petit mal (generalized absence)seizure
Sudden brief interruption of consiousness
Recurrent and can occur up to 200/day
Blank stares, eyes roll upward, eyelids flutter and complete cessation fo activity for about 3-20 seconds
- looks like weird daydreaming
Involuntary Repetitive movements may/may not occur
More common in children and adolescents (can be outgrown as an adult)
Possess “sleep spindle” patterns (3-Hz spike wave discharge which mimics slow-wave sleep)
- is not proceeded by an aura
** patients have no memory of these incidents and often negatively impacts school performances
*** symptoms are ipsilateral
** best treated with T-type calcium channel blockers
Symptoms of a grand mal (generalized tonic-clonic) seizure
Brief violent muscle contractions all over the body or individual muscles
Loss of consciousness.
*Is not proceeded by a focal seizure
** almost always presents secondary to another pathology
Etiologies of focal (partial) seizures
Caused by increases in electrical activity at the cellular level which causes inappropriate depolarization
- paroxysmal depolarizing shift (PDS)
Surround inhibition keeps this PDS within a focal point/region of the brain
Can cause a “Jacksonian march” effect if the PDS is very strong and overcomes surround inhibition
- this is an aura or feeling of anxiety/dread as the seizure continues
Etiology of secondary generalized seizures (focal-to-bilateral tonic-clinic seizures)
Is a focal seizure that escalates to the point where it involves BOTH hemispheres of the brain
Causes the uncontrolled depolarization to spread throughout connecting circuits:
- U fibers in cortical regions
- corpus callosum
- thalamocortical projections
Is almost always preceded by an aura
Etiology of primary generalized seizures (grand mal/petit mal)
Generalized seizures that tend to originate in well-connected areas within the CNS
- such as thalamus
- there is NO aura or warning signs
- can however be accompanied by a preceding feeling of apprehension or jerking of one arm
Specific differences between status epilepticus and general epilepsy
Status epilepticus
- patient is currently seizing for greater than 5 minutes or has had 2 or more seizures, or has not return to baseline brain activity after a recent seizure.
- is a medical emergency and can be fatal, requires immediate acute intervention
- goal is to stop current seizure
- first line agent is chosen by efficacy and the dosage is managed in high quantity with both IV or IM
Epilepsy
- patient has recurring seizures, but not currently
- not an emergency, but can leads to status epilepticus
- goal of treatment is to prevent a breakout
- first line agency is chosen based on efficacy: ADR ratios and is managed in low doses orally.
General principles of epilepsy treatment
Must take into consider patient factors
- age/gender
- pregnancy or wants to be pregnant
- comorbidites
- insurance
- adherence
- current meds they are on
Goal is to use just 1 drug
- only use 2 if you absolutely must (refractory seizures)
many drugs have narrow therapeutic indices and are given daily orally
** must ALWAYS titrations dose when beginning a new anti seizure drug and the blood levels of the drugs need to monitor consistently
Intractable epilepsies
Epilepsies that even with pharmacokinetic therapy, still get epilepsies
- “ untraceable seizures”
In children with these epilepsies, often see progressive brain damage
Finite treatment can be surgical resection of the affected brain region, however this is very traumatic life altering and needs to really be justified.
Generalized ADRs in all epileptic drugs
Dose dependent:
- nausea/vomiting
- dizziness/vertigo feeling
- headaches
- CNS depression
Non-adherence specific:
- rashes
- hyponatremia
Just occur sometimes:
- ocular dysfunction
- ataxia
- fatigue
- weakness
almost all are teratogenic
What must you do when switching drugs for epilepsy treatment
First drugs is always chosen based on type of seizure, patient characteristics and ADRs
- this drug is titrated to find proper dose
If the first line doesnt work:
- ALWAYS titrations the new drug while the 1st drug is being tapered slowly
- if second line fails, can use rational combinations or surgery if needed*
Carbamazepine
MOA: blocks sodium channels in epileptiform presynaptic neuron terminals
NOT a BENZO
Indications:
- focal seizures
- focal-to-bilateral tonic clinic seizures
Contraindications
- aggregates absence and myoclonic seizures
ADRs: most are dose dependent
- GI discomfort
- blurred vision
- hyponatremia
- rash
- Stevens-Johnson’s (asians and HLA-B*1502 allele patients have to worry about this more)
*strong inducer of CYP450 enzymes so must monitor when combining with drugs
Lacosamide
MOA: blocks sodium channels ion epileptiform presynaptic neurons
Indications:
- focal seizures ( only age 17+)
- focal-to-bilateral tonic-clinic seizures (requires high dose)
Contraindicated:
- patients who have phenylketonuria
Only given oral or IV
ADRs: Pretty low tolerable - nausea/vomiting - diplopia - headache
Phenytoin and fosphenytoin
Hydantoins
MOA: blocks sodium channels in epileptiform presynaptic neurons
Indications:
- focal seizures
- focal-to-bilateral tonic-clonic seizures
- *used in status epilepticus (high doses)
Contraindications:
- absence seizures
- pregnancy (develops fetal hydantoin)
Is IV/IM form only and is pretty painful to inject
- very relevant for displacement in blood concentrations
- must monitor closely for patients with hyperbillirubinemia, hypoproteinuria, warfarin and Valproic acid*
** changes kinetics based on doseage
- first-order = low concentrations
- zero-order = high concentrations
(Because of this, must be very careful in upper dose amount DONT BE TOO QUICK)
ADRs:
- nystagmus
- diplopia
- ataxia
- long term use only*
- gingival hyperplasia
- hirsustism (increase in body hair growth)
- peripheral neuropathy
- osteomalacia (lowers metabolism of Vit. D)
- agranulocytosis w/ fever and rash
Lamotrigine
MOA: blocks sodium channels in epileptiform presynaptic neurons
Indications:
- focal seizures
- absence seizures
very good choice for pregnant patients
ADRs:
- rash
- nausea/vomiting
Oxcarbazepine
MOA: blocks sodium channels in epileptiform presynaptic neuron terminals
NOT a BENZO
Indications:
- focal seizures
- focal-to-bilateral tonic clinic seizures
- especially useful if non-response to carbamazepine (since its prodrug)
Contraindications
- aggregates absence and myoclonic seizures
ADRs: most are dose dependent
- GI discomfort
- blurred vision
- hyponatremia
- rash (cross reactive with carbamazepine)
- Stevens-Johnson’s (asians and HLA-B*1502 allele patients have to worry about this more)
- CNS effects in elderly
- drug tends to do worse overall in elderly populations
Gabapentin and pregabalin
MOA: blocks high-voltage Ca2+ channels by binding to a2d subunit
DOESN’T AFFECT GABA CONCENTRATIONS
Indications:
- focal seizures
- neuralgias
- diabetic neuropathy
- anxiety
Contraindications:
- absence and myoclonic seizures
very good in elderly patients if levetiracetam fails
ADRs:
- somnolence
- dizziness
- ataxia
- headache
- permanent weight gain and peripheral edema
- Tremor
