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Epilepsy
| Question | Answer |
|---|---|
| Epilepsy | Disorder of brain function characterized by recurrent (2+) unprovoked seizures with no immediately identifiable cause |
| Seizure | Transient alteration of behavior due to disordered, synchronous, and rhythmic firing of neurons associated w/ disturbance or loss of consciousness, change in motor movements and/or altered state of consciousness |
| Acute, Reversible conditions that can cause seizures | -Traumatic brain injury -Fever -Illness (meningitis or encephalitis) -Drug intoxication (CNS stimulants) -Drug withdrawal (CNS depressents) |
| Two international seizure classifications | -Focal (Partial) - Generalized |
| Types of generalized seizures | -Absence -Myoclonic -Tonic-Clonic -Tonic -Clonic -Atonic |
| Types of focal seizures | -Without dyscognitive features -With dyscognitive features |
| Type of seizure that can evolve into bilateral convulsive seizure | Focal seizure with dyscognitive features |
| Localized focal (partial) seizure | Localized, only one part of the brain is affected |
| Asymmetric focal (partial) seizure | motor manifestation |
| Motor symptoms of focal (partial) seizures | Involvement of motor cortex that changes muscle activity (tonic and clonic). Abnormal movements may be restricted to one body part. |
| Tonic | sustained, constant contraction |
| Clonic | jerking movements |
| Non-motor symptoms of focal (partial) seizure | -Hallucinations or illusions involving the senses -Autonomic (heart rate, respiration, sweating, piloerection) -Psychic (originates in limbic system- fear, anxiety, depression, dissociative phenomena, deja vu |
| Focal without dyscognition | -Loss of consciousness -Lasts <60 seconds -No postictal symptoms -1 hemisphere |
| Focal with dyscognition | -Impaired consciousness characterized by confused, "purposeless" behavior -Lasts 1-3 minutes -Postictal confusion -25% become secondarily generalized -1 hemisphere |
| Secondarily generalized seizure | A focal seizure that may progress to generalized seizure |
| Generalized seizure | -Involves both hemispheres -Can be non-genetic or genetic -Multi-factorial (multiple genes are involved) -Non-Mendelian (skips generations) -Can be motor or non-motor |
| Tonic-clonic (grand mal) seizures | -Generalized seizure -Bilateral muscle rigidity (tonic) -Synchronous clonic movements of head and limbs (clonic) -Last 2-5 minute -Postictal drowsiness (hrs) |
| Atonic seizure | -Generalized seizure -Sudden and total loss of muscle tone resulting in head nod and/or collapse (drop attack) |
| Tonic seizure | -Generalized seizure -Sudden bilateral stiffening of limbs, most often during sleep -Less than 20 seconds |
| Myoclonic seizure | -Generalized seizure -Sudden, brief jerk of muscles of head, neck, shoulders, and limbs |
| Absence (petite mal) seizure | -Generalized seizure -Staring and general unresponsivenss -Blinking or chewing -Ends abruptly -Lasts 10-45 seconds -No postictal confusion |
| Atypical absence seizure | -Generalized seizure -Less unresponsiveness -Slower onset and cessation -similar to absence |
| Epilepsy syndromes cluster of characteristics | -Seizure types -EEG pattern -Age -Family history -Neurologic status |
| Status Epilepticus | -Seizures without recovery of consciousness between episodes -Medical emergency |
| Action Potential Steps | -Phase 0- Na+ (in) -Phase 1- K+, Cl- (out) -Phase 2- Ca2+ (in), K+ (out) -Phase 3- K+ (out) -Phase 4- Resting potential |
| Epileptiform | Seizures that are characterized by abnormal, synchronous, and rhythmic firing of neurons |
| Areas of the brain that are more prone to seizures | Cortex and hippocampus |
| Neurons that are more prone to cause seizures | pyramidal neurons |
| General considerations of antiepileptic drugs | -Na+ channel blockers -Ca2+ channel blockers -Enhance GABA synaptic neurotransmission -Antagonism of excitatory neurotransmitters |
| Adverse effects of antiepileptic drugs | -CNS depression -Headache -GI -Congitivit/behavioral effects -idosynchratic -teratogenesis |
| Valproic Acid/Divalproex Sodium MOA | -Na+ channel blocker -Ca2+ channel blocker |
| Valproic Acid/Divalproex Sodium Indications | - Effective against all seizure types -Controls both general tonic-clonic and absences in "mixed" seizures |
| Valproic Acid/Divalproex Sodium Adverse effects | -Sedation -Ataxia -Tremor -GI (n/v, heartburn, anorexia) -Weight Gain -Hepatotoxicity |
| Carbamazepine MOA | -Na+ channel blockers -Ca2+ channel blockers |
| Carbamazepine Indications | First line therapy in local seizures and generalized tonic-clonic |
| Carbamazepine Adverse Effects | -CNS -Anticholinergic effects (constipation and dry mouth) -N/V -Skin rash -Transient leukopenia, thrombocytopenia, aplastic anemia -Water retention -Metabolism 10, 11 epoxide -Autoinducer |
| Phenytoin MOA | -Na+ channel blocker |
| Phenytoin Indications | First line therapy in focal onset seizures and general tonic-clonic seizures |
| Phenytoin Adverse Effects | -Somnolence -Blurred vision -Vestibular effects -Less CNS depression than others -Lethargy and fatigue -Skin rash -Gingival hyperplasia -Vitamin D deficiency -Hirsutism |
| Fosphenytoin | -Prodrug of phenytoin -More soluble and less irritating -IV or IM -Good for status epilepticus |
| Ethosuximidie MOA | Ca2+ channel blocker |
| Ethosuximide Therapeutic Indicaitons | First line therapy in absence seizures |
| Zonisamide MOA | -Na+ channel blocker -Ca2+ channel blocker |
| Zonisamide Therapeutic Indications | -Adjunct therapy for focal seizure in adults -Broad-spectrum AED |
| Zonisamide Adverse Effects | -Solmonlence -Dizziness -Headache -Agitation -Irritability -Nausea -Anorexia -Hypersensitivity (structural similarity to sulfonamides) -Nephrolithiasis (kidney stones) |
| Benzodiazepines MOA | Increase frequency of GABA channel opening |
| Benzodiazepines Therapeutic Indications | -Chlorazepate and Clonazepam: first or second line therapy in myoclonic and atonic seizures, some use in absence seizures -Diazepam and Lorazepam: approved in status epilepticus |
| Benzodiazepines Adverse Effects | -Sedation -Tolerance -Behavioral disturbances in children (hyperactivity, aggression, irritability) |
| Phenobarbital MOA | Increase the duration (not frequency) of GABA channel opening |
| Phenobarbital Therapeutic Indications | -Second line therapy for focal seizures and general tonic-clonic seizures -Drug of choice for neonatal seizures -May be given IV for status epilepticus |
| Phenobarbital Adverse Effects | -Sedation and drowsiness -Fatigue -Behavioral problems in children -Physical dependence -Long 1/2 life (3-4 weeks to achieve steady state) |
| Gabapentin MOA | -Increase GABA synthesis -Increase levels of glutamate -Na+ channel blocker |
| Gabapentin Adverse Effects | -Fatigue -Somnolence -Dizziness -Ataxia -Aggressive behavior in children |
| Pregabalin | -Structural analog of Gabapentin -Adjunct therapy for focal seizures and neuropathic pain -Increase GABA synthesis |
| Tiagabine MOA | GABA reuptake inhibitor (GAT-1 transporter) |
| Vigabatrin MOA | Irreversible inhibitor of GABA transaminase |
| Vigabatrin Therapeutic Indications | -First-line therapy for infantile spasms -Second-line therapy for refractory focal seziures (with dyscognition) |
| Vigabatrin Adverse Effects | -Somnolence -Fatigue -Light-headedness -Depressed mood -Potentially irreversible visual field defect (9-11 months of therapy) |
| Lamotrigine MOA | -Na+ channel blocker -Inhibits glutamate release |
| Lamotrigine Therapeutic Indicaitons | -Adjunctive and monotherapy for focal seizures in adults -Second line monotherapy for generalized seizures (tonic-clonic, absence, myoclonic, and atonic) |
| Felbamate MOA | -NMDA receptor antagonist -Na+ channel blocker |
| Felbamate Therapeutic Indications | -Reserved for patients who do not respond to other AEDs -Approved for focal seizures and treating atonic seizures in patients with Lennox-Gastaut syndrome |
| Felbamate Adverse Effects | -Aplastic anemia -Hepatitis -Dizziness -Fatigue -Insomnia -Headache -Nausea -Anorexia -Weight loss |
| Topiramate MOA | -Kainate/AMPA receptor antagonist -Inhibits glutamate |
| Topiramate Therapeutic Indications | -Adjunct therapy for focal seizure in adults -Broad-spectrum AED |
| Topiramate Adverse Effects | -Ataxia -Memory and attention deficits -Confusion -Difficulty in "word-finding" -Anorexia and weight loss -Nephrolithiasis (kidney stones) |
| Rufinamide MOA | -Na+ channel blocker |
| Rufinamide Therapeutic Indications | Adjunct therapy for seizures assocaited with Lennox-Gaustaut syndrom in patients >4 yrs |
| Rufinamide Adverse Effects | -Sedation -Nausea -Headache -Doesn't alter metabolism of other AEDs |
| Ezogabine MOA | -K+ channel activator -Decreases activation threshold |
| Ezogabine Therapeutic Indications | Adjunct for focal onset seizures |
| Ezogabine Adverse Effects | -Drowsiness -Dizziness -Blurred vision -Confusion -Urinary retention |
| Cannabidiol Adverse Effects | -Drowsiness -Fatigue -Poor quality of sleep -Anorexia -Diarrhea -Transaminase elevation (especially with valproic acid) |
| Meds to treat Focal seizures | -Valproic Acid -Carbamazepine -Phenytoin -Zonisamide -Phenobarbital -Lamotrigine -Ezogabine |
| Meds to treat Generalized seizures | -Valproic Acid -Zonisamide (?) -Lamotrigine |
| Meds to treat myclonic seizures | -Chlorazepate -Clonazepam |
| Meds to treat tonic-clonic seizures | -Carbamazepine -Phenytoin -Phenobarbital |
| Meds to treat atonic seizures | -Chlorazepate -Clonazepam |
| Meds to treat status epilepticus seizures | -Fosphenytoin -Diazepam -Lorazepam -Phenobarbital |
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