Term
|
Definition
the clinical manifestation of an
abnormal and excessive excitation and
synchronization of a population of cortical neurons |
|
|
Term
|
Definition
tendency toward recurrent seizures
unprovoked by any systemic or acute neurological insults |
|
|
Term
|
Definition
| sequence of events that converts a normal neuronal network into a hyperexcitable network |
|
|
Term
| What are the 3 types of partial seizure |
|
Definition
| Simple, Complex, Secondary generalized |
|
|
Term
|
Definition
Focal with minimal spread of abnormal
discharge; normal consciousness and awareness |
|
|
Term
|
Definition
| Local onset, then spreads; Impaired consciousness |
|
|
Term
| What does complex partial seizure depend on? |
|
Definition
site of origin; degree of spread:
– Presence and nature of aura
– Automatisms
– Other motor activity |
|
|
Term
| What type of complex partial seizure is most common? |
|
Definition
|
|
Term
|
Definition
| altered state of consciousness that a person enters after experiencing a seizure; lasts between 5-30 minutes or longer; characterized by drowsiness, confusion, nausea, hypertension, headache, migraine, other disorienting symptoms; emergence from this period is often accompanied by amnesia or other memory defects. It is during this period that the brain recovers from the trauma of the seizure |
|
|
Term
| Secondarily Generalized Partial Seizure |
|
Definition
| Begins focally, w/ or w/o focal neurological symptoms; Variable symmetry, intensity, and duration of tonic (stiffening) and clonic (jerking) phases; duration up to 1-2 minutes; characterized by postictal confusion, somnolence, with or without transient focal deficit |
|
|
Term
| What are the four types of generalized seizures |
|
Definition
| Absence, Myoclonic, Atonic, Tonic-clonic |
|
|
Term
| Characteristics of absence/petit mal seizure |
|
Definition
- sudden onset and abrupt cessation
- less than 10 sec (rarely > 45 sec)
- altered consciousness
- mild clonic jerking of the eyelids or extremities, postural tone changes, autonomic phenomena and automatisms
- difficult diff. diagnosis from partial seizure
- characteristic 2.5-3.5 Hz spike and wave pattern |
|
|
Term
|
Definition
| treated as from partial leading to generalized; also seen in a wide variety of seizures |
|
|
Term
|
Definition
| sudden loss of postural tone; most often in children but may be seen in adults |
|
|
Term
| Tonic-clonic/grand mal seizure |
|
Definition
1: Tonic Phase: tonic rigidity of all extremities followed in 15-30 sec by tremor (interruption of the tonus that is relaxation)
2: Clonic Phase: massive jerking of the body that slows over 60-120 sec followed by stuporous state |
|
|
Term
| What is the most common type of adult seizure |
|
Definition
| Complex Partial Seizure (40%) |
|
|
Term
| What is the most common pediatric seizure |
|
Definition
|
|
Term
| What are the 2 ways that epilepsy occur? |
|
Definition
|
|
Term
| Describe acquired epilepsy |
|
Definition
Physical insult to the brain, such as Brain tumors, stroke, CNS infections, febrile seizures, leads to changes that cause seizures to develop
Initial seizures cause anatomical events that lead to future vulnerability
Latent period before epilepsy development |
|
|
Term
| How likely can head injuries lead to seizure? |
|
Definition
|
|
Term
| How is genetics related to epilepsy? |
|
Definition
| Mutation in a gene can cause increase in brain excitabilty or abnormality |
|
|
Term
| What are 2 examples of genetic epilepsy? |
|
Definition
- Cortical dysplasia - displacement of cortical tissue
that disrupts normal circuitry
-Benign familial neonatal convulsions |
|
|
Term
| Function of antiepileptic drug |
|
Definition
- Decreases the frequency and/or severity of seizures in people with epilepsy
- Treats the symptom of seizures, not the underlying epileptic condition |
|
|
Term
| What is the goal of antiepileptic drug |
|
Definition
maximize quality of life by minimizing
seizures and adverse drug effects |
|
|
Term
Are there are “anti-epileptogenic” drugs
available? |
|
Definition
|
|
Term
Percentage that people with epilepsy can
become seizure free with drug therapy |
|
Definition
|
|
Term
Percentage that seizures can be drastically
reduced |
|
Definition
|
|
Term
| Percentage of epileptic patients where seizures are refractory to currently available AEDs |
|
Definition
|
|
Term
| What is Acute Seizure Disorder is treated with? |
|
Definition
| Lorazepam or other Benzodiazepines |
|
|
Term
What is Chronic Generalized Seizure Disorder
treated with? |
|
Definition
|
|
Term
| What are the factors to consider when choosing AED |
|
Definition
Seizure type
Epilepsy syndrome
Pharmacokinetic profile
Interactions/other medical conditions
Efficacy
Expected adverse effects
Cost |
|
|
Term
| What is an important characteristic of AED? |
|
Definition
| Good oral absorption and bioavailability |
|
|
Term
| How are AEDs metabolized? |
|
Definition
Most metabolized in liver but some excreted unchanged
in kidneys |
|
|
Term
| When is add-on therapy used with AED? |
|
Definition
| when a single drug does not completely control seizures |
|
|
Term
| How are newer AEDs different from classic AEDs? |
|
Definition
| have less CNS sedating effects than the classical AEDs |
|
|
Term
| What is the cellular mechanism of seizure excitation? |
|
Definition
Ionic—inward Na+, Ca++ currents
Neurotransmitter—glutamate, aspartate |
|
|
Term
| What is the cellular mechanism of seizure inhibition? |
|
Definition
Ionic—inward CI-, outward K+ currents
Neurotransmitter—GABA |
|
|
Term
| What are the neuronal/intrinsic factors that modify neuronal excitabilty? |
|
Definition
-Ion channel type, number, and distribution
-Biochemical modification of receptors
-Activation of second-messenger systems
-Modulation of gene expression |
|
|
Term
What are the extra-neuronal/extrinsic factors that modify neuronal excitabilty?
|
|
Definition
-Changes in extracellular ion concentration
-Remodeling of synapse location or configuration by afferent input
-Modulation of transmitter metabolism or uptake by glial cells |
|
|
Term
| What are the mechanisms of generating hyperexcitable network |
|
Definition
| Excitatory axonal “sprouting”
Loss of inhibitory neurons
-Loss of excitatory neurons “driving” inhibitory neurons |
|
|
Term
| How can AED increase inhibitory neurotransmitter system |
|
Definition
|
|
Term
| How can AED decrease excitatory neurotransmitter system |
|
Definition
|
|
Term
| How can AED block voltage-gated inward positive currents |
|
Definition
|
|
Term
| How can AED Increase outward positive current |
|
Definition
|
|
Term
| How can AED be pleiotropic |
|
Definition
| Act via multiple mechanism |
|
|
Term
| What is brain's majoy excitatory NT |
|
Definition
|
|
Term
| WHat are the 2 groups of glutamate receptor |
|
Definition
Ionotropic—fast synaptic transmission
Metabotropic—slow synaptic transmission |
|
|
Term
| What are the inotropic receptors? |
|
Definition
| NMDA, AMPA, kainate, Gated Ca++, Gated Na+ channels |
|
|
Term
| What are the metabotropic receptors? |
|
Definition
| Quisqualate, Regulation of second messengers (cAMP and Inositol), Modulation of synaptic activity |
|
|
Term
| What are the modulators of glutamate receptors |
|
Definition
| Glycine, polyamine sites, Zinc, redox site |
|
|
Term
| What AED target NMDA/ionotropic receptors |
|
Definition
| ketamine, phencyclidine, dizocilpine, felbamate |
|
|
Term
| What is the effect of Ketamine, phencyclidine, dizocilpine? |
|
Definition
-block NMDA channel
-have anticonvulsant properties
-have dissociative and/or hallucinogenic properties
-open channel blockers |
|
|
Term
| What is the effect of Felbamate? |
|
Definition
| antagonizes strychnine-insensitive glycine site on NMDA complex |
|
|
Term
| What AED antagonize AMPA/ionotropic receptor |
|
Definition
|
|
Term
| What is the major inhibitory NT in CNS |
|
Definition
|
|
Term
| What are the two types of GABA rec. |
|
Definition
|
|
Term
| What is the function of GABAA receptor? |
|
Definition
| post-synaptic, specific recognition sites, linked to Cl channel |
|
|
Term
What is the function of GABAB receptor?
|
|
Definition
| presynaptic autoreceptors, mediated by K+ currents |
|
|
Term
|
Definition
Benzodiazepines (diazapam, clonazapam)
Barbiturates (phenobarbital, primidone)
Gabapentin
Tiagabine
Vigabatrin |
|
|
Term
| What are two of the types of Benzodiazepines? |
|
Definition
|
|
Term
| How do Benzodiazepines act on GABA rec? |
|
Definition
Increase frequency of GABA-mediated chloride
channel openings |
|
|
Term
| What are two of the types of barbiturates? |
|
Definition
|
|
Term
| How do Barbiturates act on GABA rec? |
|
Definition
-Prolong GABA-mediated chloride channel openings
-Some blockade of voltage-dependent sodium channels |
|
|
Term
| How do Gabapentin act on GABA rec |
|
Definition
May modulate amino acid transport into brain
May interfere with GABA re-uptake |
|
|
Term
How do Tiagabine act on GABA rec
|
|
Definition
| Interferes with GABA re-uptake |
|
|
Term
How do Vigabatrin act on GABA rec
|
|
Definition
| elevates GABA levels by irreversibly inhibiting its main catabolic enzyme, GABAtransaminase |
|
|
Term
| How do Na channels affect seizure |
|
Definition
Neurons fire at high frequencies during seizures
Action potential generation is dependent on Na+
channels |
|
|
Term
| How do AED affect Na channels |
|
Definition
| Use-dependent or time-dependent Na+ channel blockers reduce high frequency firing without affecting physiological firing |
|
|
Term
| What are the AED that target Na channels |
|
Definition
| Phenytoin, Carbamazepine, Oxcarbazepine, Zonisamide |
|
|
Term
| How do Phenytoin, Carbamazepine affect Na channels |
|
Definition
Block voltage-dependent sodium channels at high firing
frequencies—use dependent |
|
|
Term
How do Oxcarbazepine affect Na channels
|
|
Definition
– Blocks voltage-dependent sodium channels at high firing frequencies
– Also effects K+ channels |
|
|
Term
How do Zonisamide affect Na channels
|
|
Definition
Blocks voltage-dependent sodium channels and T-type
calcium channels |
|
|
Term
| How is abscence seizure caused? |
|
Definition
| oscillations between thalamus and cortex that are generated in thalamus by T-type (transient) Ca2+ currents |
|
|
Term
| What AED is good for blocking T-type Ca currents |
|
Definition
Ethosuximide
Note: Effectively treat Abscence seizure |
|
|
Term
| How does K channels affect seizure |
|
Definition
K+ channels have important inhibitory control over neuronal firing in CNS by repolarizing membrane to end action potentials
|
|
|
Term
| What AED act on K channels |
|
Definition
|
|
Term
| How do AED that act on K channels function |
|
Definition
| K+ channel agonists would decrease hyperexcitability in brain |
|
|
Term
| What are the pleiotropic AEDs? |
|
Definition
Felbamate
Lamotrigine
Topiramate
Valproate |
|
|
Term
| What is the action of Felbamate |
|
Definition
– Blocks voltage-dependent sodium channels at high firing frequencies
– May modulate NMDA receptor via strychnine-insensitive glycine receptor |
|
|
Term
What is the action of Lamotrigine
|
|
Definition
– Blocks voltage-dependent sodium channels at high firing frequencies
– May interfere with pathologic glutamate release
– Inhibit Ca++ channels? |
|
|
Term
What is the action of Topiramate
|
|
Definition
– Blocks voltage-dependent sodium channels at high firing frequencies
– Increases frequency at which GABA opens Cl- channels (different site than benzodiazepines)
– Antagonizes glutamate action at AMPA/kainate receptor subtype? |
|
|
Term
| What is the action of Valproate |
|
Definition
– May enhance GABA transmission in specific circuits
– Blocks voltage-dependent sodium channels
– May also augment K+ channels
– T-type Ca2+ currents? |
|
|
Term
What enzyme is most involved with drug
metabolism? |
|
Definition
|
|
Term
|
Definition
Inhibits Na+ channels—use dependent
Recommended AED during pregnacy |
|
|
Term
| What is the action of Carbamazapine |
|
Definition
First line drug for partial seizures
Inhibits Na+ channels—use dependent |
|
|
Term
| What is the action of Phenobarbital |
|
Definition
-Partial seizures, effective in neonates
-Second-line drug in adults due to more severe CNS
sedation
-Allosteric modulator of GABAA receptor (increase open
time) |
|
|
Term
| What is the first line drugs for secondary generalization |
|
Definition
carbamazepine and phenytoin (equally effective)
Valproate, phenobarbital, and primidone are also
usually effective |
|
|
Term
| Which drugs are used for partial onset seizure w/o generalization? |
|
Definition
| Phenytoin and carbamazepine |
|
|
Term
| What is the first-line of drug for tonic-clonic, myoclonic, and abscence seizures |
|
Definition
|
|
Term
| What is Status Epilepticus |
|
Definition
| More than 30 minutes of continuous seizure activity; Two or more sequential seizures spanning this period without full recovery between seizures |
|
|
Term
| What are the treatments for Status Epilepticus |
|
Definition
Diazepam, lorazapam IV (fast, short acting)
– Followed by phenytoin, fosphenytoin, or phenobarbital
(longer acting) when control is established |
|
|
Term
| Which AEDs are used for neuropathic pain |
|
Definition
| Gabapentin, carbamazepine |
|
|
Term
Which AEDs are used for bipolar disorder
|
|
Definition
| Lamotrogine, carbamazepine |
|
|
Term
Which AEDs are used for migraine
|
|
Definition
| Leviteracitam, valproate, topirimate, gaba-pentin |
|
|
