Seizure Disorders Flashcards
What is a seizure?
- Paroxysmal disorder of the CNS that is characterized by abnormal cerebral neuronal discharges with or without loss of consiousness
What are convulsions?
- Specifc seizure type where the attack is manifested by involuntary muscle contractions
What is Epilepsy?
- Repeated seizures doe to damage, irritation, and/or chemical imbalance in the brain which leads to a sudden, excessive, synchronous electrical discharge
What are the type of Generalized seizures?
- Myoclonic
- Tonic
- Clonic
- Atonic
- Tonic Clonic
What is the one thing that really classifies a seizure?
- It has to be DISORDERED, SYNCHRONOUS, RHYTHMIC firing of the brain
What are the different types of seizures?
- Focal [Simple and complex] and Generalized
What is a focal seizure?
- Focal: Originates in one part of the brain [temporal lobe] then eventually moves to the other parts [Focal to Generalized]
- Due to lesion
- Either have awareness [simple] or not [complex]
What is a generalized seizure?
- Generalized: Occurs in both sides of the brain
- “Primary”
- Genetic?
What are the genetic tests that are used for epilepsy?
- GABRA1, GABRB2, GABRB3, GABRG2
- SCN1A, SCN1B, SCN2A, SCN8A
What is the pathways for the propagation of focal and generalized seizures?
- Focal: Starts at one spot then moves to others
- Focal to Generalized
- Primary Generalized Seizures: Connections between the thalamus and the cortex
What is the purpose for the EEG within seizures?
- Electrodes are place on the top of the head being able to show the activity of the surface of the brain
What is a simple focal seizure?
- An AWARE type [know they had one]
- NO loss of consciousness
- May experience aura
What is a complex focal seizure?
- An IMPAIRED AWARENESS type
- LOSS of consciousness
- MOST common
- Aura is COMMON
- Postictal state due to impaired awareness
What is the Postictal State in seizures?
- The patient wont be able to remember what happened to them after the seizure.
- SE: Confusion, disorientation, anterograde amnesia
What is a Absence Generalized Seizure?
- Basically “Blanking Out” and coming back immediately
- NO convulsions, aura, or postictal period
What is a Generalized Tonic-Clonic
- Grand Mal
- Most dramatic of all seizures
- First Phase: Tonic - begins suddenly with diaphragm contractions [No aura]; tremor that corresponds to relaxation
- Second Phase: Clonic - Begins as relaxation becomes more prolonged; violent jerking
What is Status Epilepticus?
- A repetitive seizure activity in which the patient does not regain consciousness or its a single seizure lasting >30 minutes
- GOAL is the bring seizure under control within 60 minutes
What are a couple of important concepts to note about Epilepsies?
- One seizure =/= Epilepsy [>3 seizures]
- Drugs can be withdrawn when patient has been seizure free for 2-5 years [stopping suddenly will make the seizure worse]
What is a Paroxysmal Depolarizing Shift [PDS]?
- Large Depolarizations that trigger a burst of action potentials
- Depolarization: activation of AMPA and NMDA by glutamate and voltage gated ion Ca channels; increasing cations
What happens after the Depolarization within PDS?
- Hyperpolarization: Activation of GABA receptors by the influx of Cl- ions along with voltage and calcium-dependent K channels; decreasing K+
What are somethings that can aggravate or increase the risk of seizures?
- Alcohol, Theophylline, CNS stimulants, Bupropion, Oral Contraceptives, Withdrawl from depressants
What is the MOA for the anticonvulsant drugs?
- To stabilize and reduce neuronal excitability; reduce the E/I imbalence
- Decrease in Na Influx; Reduction in Ca influx; Enhance GABA inhibition; antagonism of excitatory transmitters
What are the targets that affect the excitatory [glutamatergic] synapse?
- Presynaptic Targets: Na & Ca Channels
- Postsynaptic Targets: NMDA & AMPA Receptors
What are the targets that affect the inhibitory [GABAergic] synapse?
- Presynaptic Targets: GABA Transporter [GAT-1] & GABA Transaminase [GABA-T]
- Postsynaptic Targets: GABAa & GABAb Receptors
What is the function of Phenytoin in seizures?
- MOA: blocks the Na gated voltage, to stop the rapid influx of Na resulting in the depolarization [not isoform: blocks Na channels in other parts of the body]
What are the side effects and/or drug interactions of Phenytoin?
- SE: Arrhythmia [not isoform], visual, ataxia, GI Symptoms, skin rash
- DI: Displaced from plamsa proteins & induces CYP450
What is the function of Carbamazepine in seizures?
- MOA: blocks the Na voltage gated channels; stopping the rapid influx of Na that resulting in the depolarization
What are some of the side effect and/or drug interactions for Cabamazepine?
- SE: blurred vision, GI issues, SJS, DRESS
- DI: Induces CYP450
What is the function of Lacosamide in seizures?
- MOA: enhance the blockage of the Na voltage gated channels
What are some of the side effects of Lacosamide?
- SE: Skin Rashes, PR interval prolongation, vision problems
What is the function of the Barbiturates [Phenobarbital and Primidone] in seizures?
- MOA: will bind to the GABAa receptor, allowing more Cl- into he neuron causing hyper-polarization in decreased excitability of the neuron
What is important to note about Phenobarbital?
- The drug of choice for infants that are up to 2 months
What are some of the side effects and/or drug interactions for the Barbiturates in seizures?
- SE: Sedation, abuse
- DI: induces CYP450
What is the function of the Benzodiazepines [Diazepiam & Clonazepam] in seizures?
- MOA: will bind to the GABAa receptor allowing more Cl- into the neuron resulting in hyper-polarization and decreases excitability of the neuron
What are some afor the side effects for the Benzodiazepines?
- SE: Sedation, abuse [not for chronic treatment]
What is important to note about Diazepam for seizures?
- Very useful for the Tonic-Clonic status epilepticus; often use as rectal gel
What is important to note about Clonazepam for seizures?
- Very useful for acute treatment of epilepsy and ABSENCE seizures
What is the function of Gabapentin and Pregabalin in seizures?
- MOA: Increase the GABA release which will decrease the presynaptic Ca2+ influx = a reduction in gluatmate [decreasing the excitatory response]
What is the side effects of Gabapentin and Pregabalin?
- Sedation, ataxia, behavioral changes
What is the function of Vigabatrin?
- MOA: Irreversible inhibitor of GABA Transminase [GABA-T]; decreases the breakdown of GABA
What are the side effects for Vigabatrin?
- Sedation, Depression, Visual problems
What is the function of Tigabine?
- MOA: Inhibits the GABA transporter [GAT-1]; will block the movement of GABA and increase its reuptake
What are the side effects of Tigabine?
- Sedation, Ataxia, nervousness, depression
What is the purpose of GABA within the brain?
- It is an inhibitory neurotransmitter that prevents the neurons from firing to rapidly; so a decrease in GABA could result in the neurons firing rapidly = degradation
What does the NMDA receptor do with in the brain?
- It will bind Glutamate resulting in an influx of Na and Ca and a efflux of K
What does the AMPA receptor do within the brain?
- It will bind Glutamate resulting in a trigger of Na and an efflux of K [same for kainate receptors]
What is the function of Felbamate in seizures?
- It is a NMDA receptor antagonist; decreasing the excessive amount of Ca that resulting in the neuronal damage
- 3rd line
What are some of the side effects that are associated with Felbamate?
- severe hepatits [why its 3rd line]
What is the function of Topiramate in seizures?
- AMPA and Kainate Receptor Antagonist; decreasing the glutamate and decreasing the neuronal damage
What are some of the side effects of Topiramate?
- Confusion, cognitive dysfunction, sedation, vision loss [patient feel worse than before]
What is the function of Ethosuximide in seizures?
- Used in ABSENCE seizure that block the T-Type Ca2+ channels in the thalamic neuron; reducing the excitability of the neuron
What is the Thalamocortical signaling mostly associated with?
- Generalized seizures
What are the side effect for Ethosuximide?
- GI issues, sedation
What is the function of Lamotrigine in seizures?
- It is used as a primary or add on therapy for focal or generalized seizures [even absence] which blocks the Na and Ca voltage gated channels
What are some of the side effect for Lamotrigine?
- Sedation, Ataxia, SJS or DRESS [because it blocks Ca channel in the skin?]
What is the function of Valproate in seizures?
- Used in focal and generalized seizures [even absence] by inhibiting Na and Ca channel and increasing GABA levels
What are some fo the side effect and/or drug interactions with Valproate?
- SE: GI issues, Hpyerammonemia, Hepatotoxicity [fatal?]
- DI: displaces phenytoin from plasma, inhibits the metabolism of Phenytoin, Carbamazepine, Phenobarbital, lamotrigine
What is the function of Levetiracetam in seizures?
- used in focal and generalized seizures that binds to the synaotic vesicular protein [SV2A] and thus will interfere with the synaptic vesicle release and neurotransmission; may also interfere with Ca entry
What drugs affect what targets within the EXCITATORY [glutamatergic] Synapse?
Presynaptic Targets:
- Na Channels: Phenytoin, Carbamazepine, Lasoamide, Lamotrigine, Valproate
- Ca Channels: Ethozuximide, Lamotrigine, Levetiracetam, Valproate
Postsynaptic:
- NMDA Receptors: Felbamate
- AMPA Receptors: Topiramate
What drugs affect what targets within the INHIBITORY [GABAergic] Synapse?
Presynaptic Targets:
- GABA Transporter: Tiagabine
- GABA Transaminase: Vigabatrin
Postsynaptic Targets:
- GABAa Receptors: Phenobarbital, Benzodiazepines
* Gabapentin and Pregabalin
What are some of the known seizure causes?
- Withdrawal, toxicity, Medical conditions, Stroke, Lowering seizure threshold
What are some of the medications that lower the seizure threshold?
- Bupropion, Clonazapine
- OTHERS: Varenicline, Carbapenems, Lithium, Tramadol
What are some of the quailty of life monitoring that we should focus on in seizures?
- Frequency, Functional Status, Social Functioning, Emotional Status, Cognition, Number of doses of drug per day, $$$$
Is/should life long treatment for serizure be necessary?
- NO: medication removeal after 2-5 years?
Seizure Recurrence - < 2 years seizure free, Onset after 12yo, 2-6 years before control, number of seizures before control, abnormal EEG…
What is Status Epilepticus in seizures?
- Continuous seizure activity lasting 5 minutes or more OR two or more discrete seizures with incomplete recovery between seizures
- Treatment: Benzo; IV Lorazapem or IM Midazolam
What are the steps in treating Status Emilepticus in seizures?
- Stablization Phase [0-5mins]: Time to seizure, Start ECG, Check Meds [to see if anything causes it]
- Initial Treatment Phase [5-20mins]: IV Lorazepam or IM Midazolam
- Second Treatment Phase [20-40mins]: IV Fospheytoin, IV Valproic Acid, IV Levetiractam
What is the phenytoin/fosphenytoin loading dose for seizures?
- Phenytoin: 20mg/kg IV up to 50mg/min IV
[can cause hypotension] - Fosphenytoin: 20mg PE/kg IV up to 150mg/min IV [Prodrug with better tolerance]
What is important to note about the Oral Phenytoin dosing within Seizures?
- MUST obtain both a phenytoin serum concentration and serum albumin concentration in the same blood draw
- Serum range: 10-20 mcg/ml
What is the Valproate loading dose for seizures?
- 15-30 mg/kg; subsequent doses = 1/2 LD up to 60mg/kg/day
- Loading Calc: Vd [0.2-0.3] x Serum Concentration [80mcg/mL] x kg
What is the seizure classifcations?
- Partial [Focal] & Generalized
What are the subclasses within Focal Seziures?
- Simple: are AWARE and conscious
- Complex: is NOT AWARE and looses consciousness
What are medications affect what CYP enzymes in seizures?
- 1A2 INDUCERS: Carbamazepine, Phenobarbital, Phenytoin,
- 2C9 INDUCERS: Carbamazepine, Phenobarbital, Phenytoin
- 3A4 INDUCERS: Carbamazepine, Lamotrigine, Oxcarbaepine, Phenobarbital, Phenytoin, Topiramate
- UGT INHIBITORS: Valproate
Why should we adjust the dosing of Lamotrigine and what/when should we change it to in seizures?
- Can cause SJS and/or DRESS
- WITHOUT UGT: 25 mg x14 d -> 50mg x14d -> 100mg x7d -> 200mg
- WITH UGT INHIBITOR [Valproate]: Same as WITHOT UGT but every other day
- WITH UGT INDUCER [Carbamazepine & Phenytoin]: Same as WITHOUT UGT but doubled
What patients are more associated with developing DRESS syndrome within seizures?
- If taking Cabamazepine, Cenboamate, Lamotrigine, Phenobarbital, Phenytoin, Valproate, Zoinsamide
- HLA-A*3101 Allele
What medications should not be used in pregnancy in seizures?
- Carbamazepine, Clonazepem, Fosphenytoin, Phenobarbital, Phenytoin, Primiodone, Topiramate = Teratogentic
- Valproate = Decrease in IQ
- SHOULD be given Folic Acid
What is VERY important to note about using any contraceptive with antiseizure medications?
- Will decrease the effectiveness of the contraceptive; MUST counsel
- Really only effects the Estrogen compounds
- COULD use progestin only
What are some of the Cardiovascular adverse effect associated with seizure medications?
- Arrhythmias [Lamotrigine, Phentyoin/Fosphenytoin]
- QTc Shortening [Rufinamide & Cenobamate]
- PR Interval Changes [Lasocsamide & Pregabalin]
- Heart Block [Lacosamide]
- Valvular Heart Disease [Fenfluramine]
What are some of the electrolyte abnormalities caused my seizure medications?
- Hyponatremia: Carbamzepine, Oxcerbazepine, Eslicarbazeipine
- Decrease Ca = Ostroprosis: Phenytoin
- Decrease bicarb = Heat Stroke: Topiramate
What are some of the Psychiatric Side effects for Antisezure medications?
- Levetiracetam: Mood issues in children
- Perampanel: Serious Neruopsychiatric event
- Valproate: Hyperammonemia
- Topiramate: cognitive disfunction is dosed to fast
