Seizure disorders & anticonvulsant meds Flashcards
We understand a seizure as _____
abnormal electrical activity in a group of CNS neurons that can lead to involuntary movements and/or sensations.
Seizures can also be defined by the
characteristic changes on an
_____ they produce
Electroencephalogram (EEG)
Electroencephalography (EEG)
● Several sensitive electrodes are placed over the scalp. The tracing received during the EEG depicts the electrical activity occurring at the surface of the brain.
● EEG waves are generally classified according to their frequency, amplitude, shape, and the sites of the scalp at which they are recorded.
● This information about waveform frequency and shape is combined with the age of the patient, state of alertness or sleep, and scalp location to determine pathologic or diagnostic significance
EEG is the essential component in the
evaluation of _____
seizures and epilepsy
The diagnostic definition of Epilepsy:
○ Disorder characterized by recurrent
seizures due to a chronic underlying
process.
○ Two or more unprovoked seizures
T/F Just because someone has a seizure, does
not mean they now have the diagnosis of
Epilepsy
T
Common Triggers of Seizures at any age
■ Metabolic disturbances, hypoglycemia, hyperglycemia, significant renal or hepatic failure
■ Medications and abused substances
Common Triggers of Seizures in infancy/early childhood
■ Fever, trauma, CNS infection, congenital CNS abnormalities, metabolic disorders
Common Triggers of Seizures in childhood
■ Epilepsy syndromes, head trauma, CNS infection, rarely CNS tumor
Common Triggers of Seizures in adolescence and early adulthood
■ Head trauma, CNS infection, brain tumor, illicit drugs, alcohol
withdrawal
■ Less commonly, epileptic syndromes
Common Triggers of Seizures in older adults
■ Cerebrovascular disease (stroke), trauma, CNS tumor, neurodegenerative disorders (such as MS)
Generalized vs. focal onset seizures
● Generalized Onset Seizures:
○ Involves both hemispheres of the brain simultaneously
○ From widespread cellular, biochemical, or structural abnormalities
● Focal Onset Seizures:
○ Seizures restricted to discrete areas of the cerebral cortex
○ Usually associated with structural abnormalities
○ Frequently have a prodrome and/or aura
Generalized seizures
- Originate at some point within and rapidly engage bilaterally distributed networks
- Can include cortical and subcortical structures
but not necessarily the entire cortex
Focal seizures
- Originate within networks limited to one hemisphere
- May be discretely localized or more widely
distributed
General onset seizure - Tonic-Clonic (Grand Mal)
○ Abrupt loss of consciousness, no aura.
Types of Seizures - Generalized
○ Tonic Phase:
■ Initial phase of increased muscle tone (tonic
contractions) that lasts 10-20 sec
■ “Ictal cry” (common due to contraction of
larynx), impaired respirations, and cyanosis
○ Clonic Phase:
■ Spasms of muscle contraction and relaxation (clonic phase) that
usually lasts < 1 minute
○ Postictal unresponsiveness, bowel/bladder incontinence, and gradual recovery of consciousness.
○ Generally fatigued after the event.
○ Around 25% of epilepsy
Generalized Onset Seizures - Motor: Atonic
○ Sudden loss of postural muscle
tone lasting 1-2 seconds. Ranges
from quick head drop to collapse
(risk of head injury).
○ Brief impairment of
consciousness, no postictal
confusion.
○ About 1% of epilepsy cases
Generalized Onset Seizures - Motor: Myoclonic
○ Short episodes of muscle contractions lasting generally only a few seconds, brief jerking
of limbs.
○ Usually begin in childhood or early adulthood.
○ About 2-3% of epilepsy.
Generalized Onset Seizures - Nonmotor
● Sudden, brief lapses of consciousness, no loss of postural control, and no postictal confusion
● Begin in childhood or early adolescence, may be confused with “day
dreaming.”
Focal Onset Seizures with normal awareness
● Consciousness is fully preserved
during seizure.
● Motor, sensory, autonomic, or psychic
symptoms without alterations of
consciousness.
● Accounts for about 14% of epilepsy.
● We further classify based on which
symptom appears at the onset of a
seizure (motor or nonmotor)
Focal Onset Seizures with impaired awareness
● Focal seizure accompanied by altered consciousness, ranging from mild
confusion to what appears to be total LOC.
● Often begins with an aura, and commonly includes involuntary automatisms
(chewing, smacking of the lips, display of emotion, running, etc).
○ May or may not have convulsions
● Patient is then confused following the seizure, and full recovery of conscious
takes from a few seconds to an hour.
● Accounts for about 36% of epilepsy cases.
Focal to bilateral seizure
● This is when any type of focal seizure “generalizes” to the whole brain.
Types of Seizures - Focal Onset
○ As the impulses spread and involve
both hemispheres, they produce a
generalized seizure (often
tonic-clonic).
Epilepsy Syndromes - Examples
● West Syndrome
● Dravet Syndrome
● Genetic Febrile Seizures Plus (GEFS+)
● Myoclonic Atonic Epilepsy (Mae) - Commonly known as Doose Syndrome
● Lennox-Gastaut Syndrome (LGS)
● Epileptic Encephalopathy with Continuous Waves During Sleep (CSWS)
● Childhood Absence Epilepsy (CAE)
● Juvenile Myoclonic Epilepsy (JME)
Febrile Seizures
● Seizures in young children with febrile illness.
○ The most common neurologic disorder of infants and young children
Febrile Seizures
● It presents as brief (<15 min), generalized tonic-clonic convulsions.
● While this can be very alarming for the parents of these young babies,
reassurance can generally be provided.
● Diagnostic efforts should focus on the cause of the fever, and treating that
cause
These do not usually lead to a diagnosis of epilepsy
Febrile seizures
Febrile seizure diagnosis
● At times, a Lumbar Puncture is considered if the diagnosis is unclear.
Keep the following in mind when considered a spinal tap:
○ Strongly consider an LP in children younger than 12 months,
because signs and symptoms of bacterial meningitis can be
minimal or absent in this age group, especially if unvaccinated
○ LP should be moderately considered in children 12-18 months of
age, again, because clinical signs/symptoms of bacterial meningitis
may be subtle in this group.
○ In children older than 18 months, the decision to perform an LP
depends on the clinical suspicion of meningitis.
Management of febrile seizures
● Supportive therapy or therapeutic interventions directed at the
condition that caused the fever is the focus of management.
● Several large studies on the risk vs benefits of treating with anticonvulsant medications say “no, not necessary for most.”
○ Neither long-term or intermittent anticonvulsant therapy is indicated for children who have experienced 1 or more simple
febrile seizures.
○ However, if preventing subsequent febrile seizures is essential for the health of the child, PO Diazepam is the treatment of choice
Status Epilepticus (SE)
a life-threatening neurologic disorder that is,
essentially, an acute prolonged seizure crisis.
Status Epilepticus (SE)
● Defined as…
○ Continuous seizures or repetitive, discrete seizures, with impaired
consciousness (seizures > 5 min in duration).
Status Epilepticus immediate treatment
● Stopping the seizure quickly is the immediate treatment of choice.
○ IV drugs are always used.
○ Also, make sure the patient is safe from convulsion trauma.
Status Epilepticus first line therapy
○ Diazepam (Valium): (5-10 mg IV q 5-10 min to a max total of 30 mg)
■ Given IV in incremental doses
■ Short-acting effect: Provides 30-40 min seizure-free interval
○ Lorazepam (Ativan): (4 mg IV x 1, may repeat once 10-15 min later)
■ Some clinicians prefer over diazepam, because it has longer
duration of action
Status Epilepticus second line therapy
○ Phenytoin (Dilantin) or Fosphenytoin (Cerebyx)
○ Levetiracetam (Keppra)
○ Valproic Acid (Depakene)
Status Epilepticus third-line therapy
○ Phenobarbital
Phenytoin and Fosphenytoin MOA
○ Phenytoin (which is PO) blocks voltage-gated Na+ channels.
■ Decreases synaptic release of glutamate (excitatory)
○ Fosphenytoin (which is IM/IV) is a more soluble prodrug of phenytoin.
■ Rapidly converted to phenytoin in the plasma
■ Commonly used if the patient is actively seizing or cannot take PO
medications (such as a critically ill ICU patient)
○ Both have high plasma protein binding, which means a long half-life but
strong potential for drug-drug interactions.
Phenytoin and Fosphenytoin indications
○ FDA indications: Seizure disorders.
■ Considered first-line choice for Focal Onset Seizures and Generalized
Motor seizures
■ Considered second-line in Status Epilepticus
Phenytoin and Fosphenytoin BBW
○ Can cause cardiovascular collapse with rapid IV infusion. Go slowly!
Phenytoin and Fosphenytoin side effects and adverse effects
○ May Worsen absence, myoclonic, and atypical seizures!
○ Nystagmus: Occurs early, no dose reduction indicated
○ Cerebellar Ataxia, Diplopia: With higher doses, dose adjustment required
○ Sedation, Tremor: At considerably higher doses, dose adjustment required
○ Teratogenicity
Phenytoin and Fosphenytoin and pregnancy
contraindicated
Carbamazepine & Oxcarbazepine
○ Block voltage-gated Na+ channels - Decreases synaptic release of glutamate (excitatory), thereby preventing overactivity.
Carbamazepine & Oxcarbazepine indications
○ First line drugs for Focal Onset Seizures and Generalized Motor Seizures
■ Should be considered first line therapy for non-elderly patients who
are not in an emergency situation
○ Trigeminal Neuralgia - First line therapy
○ Bipolar Disorder - Off-label use
Carbamazepine & Oxcarbazepine contraindications
○ Generalized non motor seizures (Absence) - Can worsen them
Carbamazepine & Oxcarbazepine BBWs
● Serious, sometimes fatal
dermatologic reactions (SJS/TEN)
can occur, especially in patients
with HLA-B1502 Allele (almost
exclusively seen in Asians).
● 5-8 times greater risk of
developing Aplastic Anemia or
Agranulocytosis while on this
medication
Carbamazepine & Oxcarbazepine and pregnancy
Contraindicated
Valproic Acid (Depakene) MOA
○ Blocks voltage-gated Na+ channels - Decreases synaptic release of
glutamate (excitatory), and also blocks neuronal calcium channels.
○ Increases GABA concentrations (unknown mechanism)
○ Like Phenytoin, highly bound to plasma proteins
Valproic Acid (Depakene) indications
○ Generalized Motor Seizures - A First-line drug
○ Generalized non motor seizures (Absence) - A First-line drug in adults,
second line in children
○ Focal Onset Seizures - Second-line drug
○ Bipolar Disorder
Valproic Acid (Depakene) BBWs
○ Serious or fatal hepatotoxicity can occur, usually in first 6 months of Tx
○ Increased risk of hepatotoxicity in rare Mitochondrial diseases
○ Can cause major congenital malformations - High risk to fetus
○ Life-threatening pancreatitis with or without hemorrhage can occur
Ethosuximide (Zarontin) MOA
○ Blocks voltage-gated Na+ and Ca2+ channels, which decreases the
synaptic release of excitatory glutamate.
Ethosuximide (Zarontin) indications
○ Absence Seizures: A first drug of choice in children
○ Also used in adults – But Valproic Acid is often first choice in adults
Ethosuximide (Zarontin) and pregnancy
○ Benefits likely outweigh risks
during pregnancy, although there
is likely some risk.
Phenobarbital MOA
○ As a barbiturate, enhances inhibitory action
of γ-aminobutyric acid (GABA) by binding to
and increasing activity of the GABA receptor.
■ Increased GABA activation = Increased
inhibition
Phenobarbital indications
○ Focal Onset Seizures - A 2nd line medication
○ Generalized Onset Motor Seizures - A 2nd line medication
○ Status Epilepticus - A 3rd line medication
○ Occasionally used to cause sedation
Phenobarbital side effects and adverse effects
○ CNS Depression: Graded, dose dependent (dangerous)
○ Paradoxical irritability and hyperactivity in children (like Benadryl)
○ Ataxia, Cognitive Impairment: Agitation and confusion worse in elderly
○ Dependence, Abuse: Dangerous abrupt withdrawal, must taper
○ Induction of Liver Enzymes and DDIs
Gabapentin (Neurontin) MOA
○ GABA analog - Alters GABA metabolism or its release.
○ Pharmacokinetics and Pharmacodynamics: Not metabolized by liver and does
not induce liver enzymes (generally well tolerated by elderly)
Gabapentin (Neurontin) indications
○ Focal Onset Seizures: Adjunct therapy, does not work well as monotherapy
○ Post-Herpetic Neuralgia
○ Neuropathic Pain
○ Peripheral Neuropathies, Fibromyalgia
Gabapentin (Neurontin) contraindications
○ Avoid abrupt withdrawal, need to taper off slowly, over about 2-3 weeks.
○ Caution in severe renal impairment, ETOH abuse, drug abuse history.
Gabapentin (Neurontin) side effects
○ Dizziness (most common side effect)
○ Sedation or drowsiness (also very common)
○ Fatigue or somnolence (common)
○ Ataxia or Tremor
○ Anaphylaxis and/or Angioedema
Pregabalin (Lyrica) MOA
○ GABA analog closely related to gabapentin, and also blocks
voltage-gated Ca2+ channels.
■ Decreases synaptic release of excitatory glutamate
○ Not metabolized by the liver and does not induce liver enzymes,
generally well tolerated by elderly
Pregabalin (Lyrica) indications
○ Focal Onset Seizures: Adjunct therapy, does not work well as
monotherapy
○ Also like Gabapentin, can work well for Fibromyalgia, Post-Herpetic
Neuralgia, Neuropathic Pain, and Peripheral Neuropathy
Lamotrigine (Lamictal) indications
○ Focal Onset Seizures: Usually adjunct therapy, but can be successful as
monotherapy.
○ Generalized Motor and Nonmotor Seizures: Usually adjunct therapy, but
can be successful as monotherapy.
○ Bipolar Disorder: Maintenance therapy, which is more effective at
preventing depression than mania. Not for acute mania
Lamotrigine (Lamictal) side effects and adverse effects
○ Severe rash, including Stevens-Johnson Syndrome
■ This is a Black Box Warning!
○ Dizziness (very common)
○ Diplopia (common)
○ Headache (common)
○ Ataxia, blurred vision, rhinitis, somnolence (less common)
Levetiracetam & Brivaracetam MOA
○ Possible GABA analogs, may bind benzodiazepine receptor.
■ Increased GABA activation = Increased inhibition
Levetiracetam & Brivaracetam indications
○ Focal Onset Seizures: Adjunct therapy, but can work well as monotherapy
○ Generalized Onset Seizures: Adjunct, but can work well as monotherapy
○ IV form can be used for status epilepticus
○ Commonly used because it is not metabolized by and does not affect
the liver, and does not need to be monitored (no need to check serum levels for the most part)
Levetiracetam & Brivaracetam side effects
○ Headache (most common)
○ Infections
○ Asthenia
○ Somnolence/Drowsiness
○ Nasopharyngitis or cough
○ Truly, minimal adverse reactions and
generally well-tolerated
Topiramate (Topamax) MOA
○ Blocks voltage-gated Na+ channels - Decreases synaptic release of
excitatory glutamate.
○ Also seems to act as a GABA analog - Enhances its inhibitory activity
Topiramate (Topamax) indications
○ Focal Onset Seizures: Adjunct therapy, but sometimes used as monotherapy
○ Generalized Onset Motor Seizures: Adjunct therapy, but sometimes used as monotherapy
○ Migraine Prophylaxis
○ Off-label use for PTSD-related nightmares, and weight loss
Topiramate (Topamax) side effects
○ Decrease in serum bicarbonate (causes metabolic acidosis) (7-67%)
○ Drowsiness (common) - Nicknamed “Dopamax” for a reason
○ Dizziness (common)
○ Ataxia
○ Nervousness
○ Paresthesias
○ Psychomotor slowing (“Dopamax”)
Zonisamide (Zonegran) MOA
○ Blocks voltage-gated neuronal sodium and calcium channels, which
decreases the synaptic release of excitatory glutamate.
Zonisamide (Zonegran) indications
○ Focal Onset Seizures: Adjunct therapy in patients greater than 16 years old
Zonisamide (Zonegran) side effects
○ Lots and lots of possible drug interactions- Be sure to always check.
○ Dizziness, Sedation, Ataxia, Tremor are the most common.
○ Potential for Stevens-Johnson syndrome and toxic epidermal necrolysis.
○ Metabolic acidosis is possible
Lacosamide (Vimpat) indications
- Can be given IV or oral
○ Focal Onset Seizures: Monotherapy or adjunctive therapy
○ Generalized Onset Motor Seizures: Adjunctive therapy
