NSeizures and Epilepsy: Pathophysiological and Pharmacological Perspectives
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Questions and Answers

Which of the following factors can alter the properties of neuronal networks, potentially leading to hyperexcitability, seizures, and epilepsy? (Select one)

  • Balanced excitatory and inhibitory activity in neurons
  • Damage to the brain (correct)
  • Glial cell support
  • Calcium imaging in neurons

    • Which of the following supports proper brain function by balancing excitatory and inhibitory signals?

  • Only excitatory neurons
  • Only inhibitory neurons
  • A combination of excitatory and inhibitory neurons, along with glial cells (correct)
  • Glial cells only

    • Which of the following factors is NOT commonly known to alter the properties of neuronal networks?

  • Inherited gene mutations
  • Brain damage
  • Glial cell malfunctions (correct)
  • Developmental abnormalities

    • Inherited gene mutations that alter neuronal network properties often affect genes that encode which of the following?

    <p>Ion channels</p> Signup and view all the answers

    What is a potential consequence of altered neuronal network properties in the brain?

    <p>Hyperexcitability and seizures</p> Signup and view all the answers

    Cultured cortical neurons expressing a fluorescent reporter of calcium (Ca²+) are primarily used to observe: A. Changes in neuron size B. Network firing under normal conditions C. Genetic mutations in neurons D. Glial cell activity

    <p>Network firing under normal conditions</p> Signup and view all the answers

    Which neurotransmitters are primarily associated with increased excitation in neuronal networks?

    <p>Glutamate and aspartate</p> Signup and view all the answers

    Hyperexcitability in neuronal networks can be due to which of the following ionic imbalances?

    <p>Increased inward Na+ and Ca²+ currents</p> Signup and view all the answers

    Which neurotransmitter is primarily responsible for inhibitory effects in the brain, helping to prevent hyperexcitability?

    <p>GABA</p> Signup and view all the answers

    How do several anti-convulsant drugs work to reduce hyperexcitability in the brain?

    <p>By promoting GABA function</p> Signup and view all the answers

    Mutations in genes encoding which type of channels can lead to brain hyperexcitability?

    <p>Voltage/ligand-gated ion channels</p> Signup and view all the answers

    Which of the following statements is true regarding seizure triggers and inhibitors?

    <p>GABA antagonists trigger seizures, while glutamate antagonists stop seizures.</p> Signup and view all the answers

    Which of the following best describes 'channelopathies'?

    <p>Disorders caused by mutations in genes encoding ion channels</p> Signup and view all the answers

    Which mutation in the following genes is associated with 'generalized epilepsy with febrile seizures plus'?

    <p>SCN1B</p> Signup and view all the answers

    Mutations in the genes KCNQ2 and KCNQ3 are associated with which of the following conditions?

    <p>Benign familial neonatal convulsions</p> Signup and view all the answers

    What is the primary effect of mutations in ion channel genes on neuronal networks?

    <p>Altered ion flow leading to hyperexcitability</p> Signup and view all the answers

    Which ion channel mutation is linked to febrile seizures and generalized epilepsy?

    <p>SCN1B mutation</p> Signup and view all the answers

    Benign familial neonatal convulsions are commonly associated with mutations in which type of ion channels?

    <p>Potassium (K⁺) channels</p> Signup and view all the answers

    Which of the following is a potential result of injury-induced hyperexcitability in the brain?

    <p>Increased excitatory neuron activity</p> Signup and view all the answers

    Which type of neuron is primarily responsible for amplifying signals that can lead to hyperexcitability after brain injury?

    <p>Excitatory interneurons</p> Signup and view all the answers

    What can happen to excitatory and inhibitory balance in the brain following an injury?

    <p>A shift toward excitatory dominance</p> Signup and view all the answers

    Injury-induced hyperexcitability often involves which type of synaptic activity?

    <p>Increased excitatory synaptic input</p> Signup and view all the answers

    Following a brain injury, hyperexcitability may be exacerbated by dysfunction in which of the following cells that normally support neurons?

    <p>All of the above</p> Signup and view all the answers

    What is the most common pathological finding in temporal lobe epilepsy (TLE)?

    <p>Hippocampal sclerosis</p> Signup and view all the answers

    Damage to which brain region is associated with hyper-excitable networks and often leads to temporal lobe epilepsy?

    <p>Hippocampus</p> Signup and view all the answers

    Which of the following glial cell dysfunctions can contribute to neuronal hyperexcitability?

    <p>Decreased glutamate uptake</p> Signup and view all the answers

    Chronic glial dysfunction can lead to hyperexcitability through which of the following mechanisms?

    <p>Blood-brain barrier (BBB) damage</p> Signup and view all the answers

    How does decreased glutamate uptake by glial cells affect neuronal networks?

    <p>It increases hyperexcitability by raising extracellular glutamate levels</p> Signup and view all the answers

    Which of the following is a result of chronic glial dysfunction in the brain?

    <p>Excessive release of pro-inflammatory molecules</p> Signup and view all the answers

    What is the effect of decreased neuronal GABA synthesis in the context of glial dysfunction?

    <p>Increased excitatory signaling and hyperexcitability</p> Signup and view all the answers

    According to the International League Against Epilepsy (ILAE), a seizure is defined as:

    <p>A transient occurrence of signs and/or symptoms due to abnormal, excessive, or hyper-synchronous neuronal activity</p> Signup and view all the answers

    Which of the following best describes the nature of a seizure?

    <p>Transient and abnormal neuronal activity</p> Signup and view all the answers

    The term 'hyper-synchronous' in the context of a seizure refers to:

    <p>Neurons firing in a highly coordinated and simultaneous manner</p> Signup and view all the answers

    Which organization is responsible for defining the standard terms related to epilepsy and seizures?

    <p>International League Against Epilepsy (ILAE)</p> Signup and view all the answers

    Which of the following is NOT a characteristic of a seizure? A. Excessive neuronal activity B. Hyper-synchronous neuronal firing C. Permanent neurological damage D. Transient signs and/or symptoms

    <p>Permanent neurological damage</p> Signup and view all the answers

    Which classification describes a seizure that begins in one part of the brain and may spread to affect both sides?

    <p>Focal to bilateral tonic-clonic</p> Signup and view all the answers

    Which type of seizure is characterized by a brief loss of awareness without a loss of postural tone?

    <p>Absence (Nonmotor)</p> Signup and view all the answers

    In a focal onset seizure with impaired awareness, what occurs?

    <p>The patient loses consciousness</p> Signup and view all the answers

    Which of the following is NOT considered a motor seizure type?

    <p>Absence</p> Signup and view all the answers

    A seizure characterized by a sudden, brief, shock-like muscle contraction is classified as:

    <p>Myoclonic</p> Signup and view all the answers

    What is the primary characteristic of a tonic seizure?

    <p>Sustained muscle contractions without a clonic phase</p> Signup and view all the answers

    Which type of seizure is often referred to as a "drop attack" due to sudden loss of postural tone?

    <p>Atonic</p> Signup and view all the answers

    Which type of seizure involves both tonic and clonic phases, leading to convulsions and loss of consciousness?

    <p>Tonic-clonic (grand mal)</p> Signup and view all the answers

    How is a focal onset seizure where the patient remains aware described?

    <p>Simple partial seizure</p> Signup and view all the answers

    A seizure that starts without a clear focal or generalized origin is classified as:

    <p>Unknown onset</p> Signup and view all the answers

    Which type of seizure is characterized by rhythmic jerking movements without a preceding tonic phase?

    <p>Clonic</p> Signup and view all the answers

    In the classification of focal onset seizures, what does "aware" indicate?

    <p>The patient remains conscious during the seizure</p> Signup and view all the answers

    What type of seizure includes both motor and nonmotor classifications?

    <p>Focal onset seizures</p> Signup and view all the answers

    Which of the following seizure types is known for a sudden loss of muscle tone that causes the person to collapse?

    <p>Atonic</p> Signup and view all the answers

    Which classification of seizure involves both sides of the brain from the start?

    <p>Generalized onset</p> Signup and view all the answers

    What distinguishes a generalized absence seizure from other types of seizures?

    <p>Brief loss of awareness without loss of posture</p> Signup and view all the answers

    In focal onset seizures with motor onset, which of the following is commonly observed?

    <p>Jerking or twitching movements in one area of the body</p> Signup and view all the answers

    What type of seizure is commonly associated with a "blank stare" and a lack of awareness of surroundings?

    <p>Absence (petit mal)</p> Signup and view all the answers

    Which of the following best describes an atonic seizure?

    <p>Complete loss of muscle tone, causing collapse</p> Signup and view all the answers

    Which feature is characteristic of a tonic seizure?

    <p>Sustained muscle contraction with extension and arching of the back</p> Signup and view all the answers

    Which of the following describes clonic activity during a seizure?

    <p>Rhythmic contracting and relaxing of muscles</p> Signup and view all the answers

    Which clinical feature often occurs immediately following a seizure (post-ictal state)?

    <p>Disorientation and confusion</p> Signup and view all the answers

    Which of the following may be a sign that a seizure has spread to the motor cortex?

    <p>Convulsions</p> Signup and view all the answers

    Which of these is a common clinical feature of a seizure involving disordered thought processes?

    <p>Déjà vu</p> Signup and view all the answers

    Which of the following might be observed as a sequential behavior during seizure spread?

    <p>Progression from fingers to wrist to elbow</p> Signup and view all the answers

    Which feature is most likely to occur as a result of a tonic-clonic seizure?

    <p>Eye-rolling and eyelid flickering</p> Signup and view all the answers

    Which of the following symptoms is commonly associated with the post-ictal phase of a seizure?

    <p>Urinary incontinence</p> Signup and view all the answers

    What is a common feature of tonic-clonic convulsions?

    <p>Convulsions involving both tonic and clonic phases</p> Signup and view all the answers

    During a seizure, what behavior might suggest activation of the motor cortex?

    <p>Sequential spread of convulsive movements</p> Signup and view all the answers

    Staring spells, also known as absence seizures, are primarily associated with abnormal electrical activity in which part of the brain?

    <p>Frontal lobes</p> Signup and view all the answers

    Déjà vu, a sensation of having experienced the present situation before, is commonly associated with seizures originating from which brain area?

    <p>Temporal lobe</p> Signup and view all the answers

    Loss of consciousness during a seizure is most commonly due to what phenomenon?

    <p>Spread of abnormal electrical activity throughout the brain</p> Signup and view all the answers

    Convulsions resulting from seizure activity occur when the electrical activity spreads to which area of the brain?

    <p>Motor cortex</p> Signup and view all the answers

    Urinary incontinence and tongue biting are commonly associated with which type of seizure?

    <p>Generalized tonic-clonic seizures</p> Signup and view all the answers

    Eye-rolling during a seizure is typically seen in which type of seizure activity?

    <p>Generalized seizures</p> Signup and view all the answers

    Eyelid flickering can occur in various types of seizures and indicates abnormal activity in which regions?

    <p>Areas controlling eye movements</p> Signup and view all the answers

    The sensation of déjà vu during a seizure suggests involvement of which specific brain process?

    <p>Memory processing</p> Signup and view all the answers

    Which of the following clinical features is often seen during the postictal state following a seizure?

    <p>Confusion and disorientation</p> Signup and view all the answers

    What is the primary mechanism leading to convulsions during a generalized tonic-clonic seizure?

    <p>Widespread activation of the motor cortex</p> Signup and view all the answers

    What defines status epilepticus?

    <p>A series of seizures without recovery lasting more than 5 minutes</p> Signup and view all the answers

    What is the primary reason for treating status epilepticus as a medical emergency?

    <p>It can lead to significant morbidity and mortality</p> Signup and view all the answers

    What is a potential consequence of prolonged seizure activity in status epilepticus?

    <p>Neuronal death by excitotoxicity</p> Signup and view all the answers

    Why do normal seizure self-termination mechanisms fail during status epilepticus?

    <p>There is a prolonged imbalance between excitatory and inhibitory activity</p> Signup and view all the answers

    Which of the following is a common treatment approach for status epilepticus? A. Initiating a ketogenic diet B. Immediate administration of anticonvulsants C. Monitoring without intervention D. Surgical intervention

    <p>Immediate administration of anticonvulsants</p> Signup and view all the answers

    What are the long-term risks associated with untreated status epilepticus?

    <p>Development of chronic epilepsy and cognitive deficits</p> Signup and view all the answers

    What is a significant factor that contributes to mortality in patients experiencing status epilepticus?

    <p>Recurrent seizures without treatment</p> Signup and view all the answers

    Which of the following statements about the treatment of status epilepticus is true?

    <p>It is crucial to initiate treatment immediately to prevent brain damage</p> Signup and view all the answers

    Which of the following statements is true regarding brief, isolated seizures?

    <p>They may negatively impact brain function.</p> Signup and view all the answers

    Severe, intractable epilepsy is associated with which of the following changes in the brain?

    <p>Increased neuronal death and gliosis</p> Signup and view all the answers

    What does Gower's hypothesis suggest regarding seizures and their effects?

    <p>Frequent seizures may lead to more seizures.</p> Signup and view all the answers

    What is SUDEP?

    <p>Sudden unexpected death in epilepsy</p> Signup and view all the answers

    Altered gene expression in severe epilepsy can result in which of the following?

    <p>Cellular changes associated with seizure activity</p> Signup and view all the answers

    Which of the following changes is associated with the remodeling of synapses in severe epilepsy?

    <p>Altered connectivity and function of neurons</p> Signup and view all the answers

    The effects of epileptic seizures on the brain can be described as:

    <p>Specific to the patient, seizure type, and epilepsy type</p> Signup and view all the answers

    What does an electroencephalogram (EEG) record?

    <p>Weak electrical activity generated by the brain</p> Signup and view all the answers

    How are currents recorded in an EEG primarily generated?

    <p>By the collective activity of neurons passing through the extracellular space</p> Signup and view all the answers

    What is a primary advantage of EEG in terms of temporal resolution?

    <p>It has good temporal resolution, allowing detection of rapid changes in brain activity.</p> Signup and view all the answers

    Which of the following describes the spatial resolution of EEG?

    <p>Poor spatial resolution</p> Signup and view all the answers

    What physiological basis generates the extracellular dipole detected in EEG?

    <p>EPSPs from similarly oriented pyramidal cells in the cortex</p> Signup and view all the answers

    In which layer of the cortex do pyramidal cells that contribute to the EEG signal primarily reside?

    <p>Layer 5</p> Signup and view all the answers

    What is the primary limitation of EEG concerning spatial resolution?

    <p>It is limited in pinpointing the exact location of brain activity due to the spread of electrical signals through the scalp.</p> Signup and view all the answers

    What type of electrical field does an EEG primarily detect?

    <p>Electrical fields generated by similarly oriented pyramidal cells in the cortex</p> Signup and view all the answers

    In the 10-20 system of EEG electrode placement, which numbering indicates electrodes on the left side of the head?

    <p>Odd-numbered leads</p> Signup and view all the answers

    What is the primary diagnostic value of EEG?

    <p>Analyzing the frequency and amplitude of brain waves</p> Signup and view all the answers

    During seizures, EEG typically shows which of the following characteristics?

    <p>Repetitive generalized or focal spikes and sharp waves</p> Signup and view all the answers

    A seizure that begins in a specific area of the brain and may affect consciousness is classified as which type?

    <p>Focal Onset</p> Signup and view all the answers

    What is the minimum frequency that characterizes seizure activity during the ictal phase in an EEG?

    <p>3 Hz</p> Signup and view all the answers

    Which of the following statements about generalized onset seizures is TRUE?

    <p>They involve widespread activation across both hemispheres.</p> Signup and view all the answers

    What is the duration that defines the ictal phase of a seizure when analyzing EEG activity?

    <p>Greater than 10 seconds</p> Signup and view all the answers

    What is the primary diagnostic value of EEG in seizure detection?

    <p>Analyzing the frequency and amplitude of brain waves</p> Signup and view all the answers

    In a generalized onset seizure, where does the epileptiform EEG activity begin?

    <p>Simultaneously in both hemispheres</p> Signup and view all the answers

    Which characteristic is TRUE regarding generalized onset seizures?

    <p>They begin without a clear focal point.</p> Signup and view all the answers

    What defines a focal onset seizure?

    <p>It originates in one or more specific brain regions (foci).</p> Signup and view all the answers

    Which of the following statements is correct regarding the spread of focal onset seizures?

    <p>They can spread to involve the entire brain, leading to generalized seizures.</p> Signup and view all the answers

    Focal to bilateral tonic-clonic seizures refer to which of the following?

    <p>A seizure that starts focally and then spreads to both hemispheres, resulting in tonic-clonic activity.</p> Signup and view all the answers

    What is the primary neurophysiological tool used for the diagnosis of epilepsy?

    <p>EEG (Electroencephalogram)</p> Signup and view all the answers

    When is the assessment of epilepsy typically performed using EEG?

    <p>During interictal activity (between seizures)</p> Signup and view all the answers

    Which of the following is NOT considered a transient abnormality or discharge in EEG?

    <p>Background activity abnormalities</p> Signup and view all the answers

    What type of abnormality might be observed in background activity during an EEG of a patient with epilepsy?

    <p>Slowing not consistent with the behavioral state</p> Signup and view all the answers

    In an EEG of a patient with idiopathic (primary generalized) epilepsy, what might be seen on a relatively normal background?

    <p>A burst of generalized epileptiform activity</p> Signup and view all the answers

    Which statement is true regarding the odd and even-numbered leads in EEG electrode placement?

    <p>Odd-numbered leads indicate left side placements, and even-numbered leads indicate right side placements.</p> Signup and view all the answers

    What is the purpose of video analysis in the context of epilepsy?

    <p>To visually record and analyze seizure activity</p> Signup and view all the answers

    Which imaging technique is primarily used to identify structural abnormalities in the brain?

    <p>Computed Tomography (CT)</p> Signup and view all the answers

    What does Magnetic Resonance Imaging (MRI) primarily help identify?

    <p>Structural abnormalities such as scar tissue or tumors</p> Signup and view all the answers

    What does functional MRI (fMRI) measure in the brain?

    <p>Blood flow to active brain regions (BOLD)</p> Signup and view all the answers

    What type of markers does Positron Emission Tomography (PET) inject to assess neural function?

    <p>Labelling markers like O2 and 2-deoxyglucose (2DG)</p> Signup and view all the answers

    Which of the following investigations is used to identify both structural and functional abnormalities in the brain?

    <p>fMRI</p> Signup and view all the answers

    What is the primary goal of brain imaging in the context of epilepsy?

    <p>To identify structural and functional abnormalities</p> Signup and view all the answers

    What is a key characteristic of psychogenic non-epileptic seizures (PNES)?

    <p>They are typically triggered by psychological stress or trauma.</p> Signup and view all the answers

    Which of the following is NOT a feature that may help differentiate PNES from epileptic seizures?

    <p>Postictal confusion lasting several hours</p> Signup and view all the answers

    During an EEG monitoring, what is typically observed in a patient experiencing a psychogenic non-epileptic seizure?

    <p>Normal EEG activity during the episode</p> Signup and view all the answers

    What can be a useful method to help differentiate between true seizures and PNES?

    <p>Video monitoring of the episodes to observe behavior</p> Signup and view all the answers

    Which of the following statements about non-epileptic attack disorder (NEAD) is true?

    <p>Patients may have a history of psychiatric disorders.</p> Signup and view all the answers

    Which of the following symptoms is more commonly associated with psychogenic non-epileptic seizures than with epileptic seizures?

    <p>Fluctuating levels of consciousness during the episode</p> Signup and view all the answers

    What is the primary approach to managing patients with psychogenic non-epileptic seizures?

    <p>Psychological therapy and support</p> Signup and view all the answers

    What is the most appropriate initial test for a newly diagnosed epilepsy patient?

    <p>EEG to assess for epileptiform activity</p> Signup and view all the answers

    What is the recommended guidance for the patient regarding driving after experiencing seizures?

    <p>She should refrain from driving until she has been seizure-free for at least 6 months.</p> Signup and view all the answers

    Which seizure type is characterized by sudden episodes of muscle stiffness, followed by jerking movements?

    <p>Complex partial seizure</p> Signup and view all the answers

    In an elderly patient with memory issues and confusion, what is the most likely underlying cause of his seizures?

    <p>Subdural hematoma</p> Signup and view all the answers

    What is the most likely diagnosis for a child who exhibits right arm jerking followed by a loss of consciousness?

    <p>Focal onset seizure</p> Signup and view all the answers

    What type of seizure is characterized by sudden muscle weakness causing falls, without loss of consciousness?

    <p>Atonic seizure</p> Signup and view all the answers

    For a patient whose epilepsy has worsened despite proper medication adherence, what is the best management step?

    <p>Increase the dose of her current antiepileptic medication</p> Signup and view all the answers

    What investigation is most appropriate to confirm the diagnosis of a patient exhibiting episodes of staring and unresponsiveness?

    <p>Electroencephalogram (EEG)</p> Signup and view all the answers

    What is the most likely trigger for a seizure experienced by an 18-year-old who felt lightheaded and fatigued before the episode?

    <p>Dehydration</p> Signup and view all the answers

    What type of seizure is characterized by rhythmic jerking movements with no preceding tonic phase?

    <p>Myoclonic seizure</p> Signup and view all the answers

    What does the patient likely experience after a generalized tonic-clonic seizure?

    <p>Prolonged confusion and disorientation</p> Signup and view all the answers

    What distinguishes absence seizures from other types of seizures?

    <p>Brief loss of awareness without confusion</p> Signup and view all the answers

    In the case of prolonged seizures in an individual with epilepsy, what is the most urgent management step?

    <p>Administer intravenous benzodiazepines</p> Signup and view all the answers

    During a seizure characterized by shaking and falling, what main aspect indicates a diagnosis of epilepsy in the child?

    <p>Loss of consciousness during episodes</p> Signup and view all the answers

    What type of seizure is most likely if a patient experiences muscle jerks and a feeling of being partially aware?

    <p>Focal onset impaired awareness seizure</p> Signup and view all the answers

    What should be considered when a previously stable patient with epilepsy experiences a prolonged seizure?

    <p>Possible underlying illness or stress</p> Signup and view all the answers

    What is a significant difference between myoclonic seizures and generalized tonic-clonic seizures?

    <p>Myoclonic seizures present as brief muscle jerks</p> Signup and view all the answers

    What is the characteristic feature of episodes described in absence seizures?

    <p>Loss of awareness without significant movement</p> Signup and view all the answers

    What is the primary consideration for starting antiseizure medication after a first unprovoked seizure?

    <p>The presence of underlying causes, such as a tumor</p> Signup and view all the answers

    What percentage does antiseizure medication reduce the risk of subsequent seizures after a first unprovoked seizure?

    <p>35%</p> Signup and view all the answers

    How does the quality of life associated with immediate antiseizure medication compare to deferred treatment?

    <p>There is no difference in quality of life between the two approaches</p> Signup and view all the answers

    Which of the following is NOT considered a high-risk factor for seizure recurrence after a first unprovoked seizure?

    <p>Previous history of migraines</p> Signup and view all the answers

    What is the sufficient criterion for diagnosing epilepsy?

    <p>Two unprovoked seizures occurring more than 24 hours apart</p> Signup and view all the answers

    What is the cumulative risk percentage of experiencing another seizure within 10 years after one unprovoked seizure, with structural lesions present?

    <p>26%</p> Signup and view all the answers

    When is antiseizure medication therapy typically suggested after a first unprovoked seizure?

    <p>When there is evidence of high risk for recurrent seizures</p> Signup and view all the answers

    Which factor is most likely to influence the decision to initiate antiseizure medication in a patient after a first unprovoked seizure?

    <p>The presence of relevant structural causes</p> Signup and view all the answers

    Which of the following antiseizure medications primarily acts on voltage-dependent sodium channels?

    <p>Lamotrigine</p> Signup and view all the answers

    What is the primary mechanism of action of ethosuximide?

    <p>Inhibition of T-type calcium channels</p> Signup and view all the answers

    Which class of medications is known to enhance GABAergic activity?

    <p>Benzodiazepines</p> Signup and view all the answers

    Perampanel primarily targets which type of receptor?

    <p>Glutamate receptors</p> Signup and view all the answers

    Brivaracetam and levetiracetam share a common mechanism of action. What is it?

    <p>Modulation of synaptic vesicle protein SV2A</p> Signup and view all the answers

    Which of the following medications can target multiple mechanisms of action?

    <p>Levetiracetam</p> Signup and view all the answers

    Carbamazepine primarily functions by blocking which type of channels?

    <p>Voltage-dependent sodium channels</p> Signup and view all the answers

    Phenobarbital enhances the effect of which neurotransmitter?

    <p>GABA</p> Signup and view all the answers

    How many members are there in the voltage-gated sodium channel (Nav) gene family?

    <p>Nine</p> Signup and view all the answers

    Which voltage-gated sodium channel subtypes are specifically involved in epilepsy?

    <p>Nav1.2, Nav1.3, Nav1.6</p> Signup and view all the answers

    What is the primary action of lamotrigine on voltage-gated sodium channels?

    <p>Binds to the fast inactivated state, slowing recovery</p> Signup and view all the answers

    Which of the following drugs is known to inhibit Nav1.2 channels?

    <p>Lamotrigine</p> Signup and view all the answers

    What is the consequence of blocking voltage-gated sodium channels during a seizure?

    <p>Reduced influx of Na+</p> Signup and view all the answers

    Which sodium channel subtype does rufinamide have some activity on?

    <p>Nav1.1 and Nav1.6</p> Signup and view all the answers

    What structural component of voltage-gated sodium channels contributes to their function?

    <p>A single alpha-subunit with four domains</p> Signup and view all the answers

    What happens to the sodium channels during a seizure in relation to lamotrigine?

    <p>Their blockade occurs during seizure activity</p> Signup and view all the answers

    What is the principal way antiseizure medications, such as Lamotrigine and Phenytoin, act on voltage-gated sodium channels?

    <p>They bind to Nav1.2 channels in their fast-inactivated state.</p> Signup and view all the answers

    Which Nav channel is NOT implicated in epilepsy?

    <p>Nav1.5</p> Signup and view all the answers

    How does Rufinamide contribute to its antiseizure effects?

    <p>By acting on Nav1.1 and Nav1.6 channels.</p> Signup and view all the answers

    What physiological effect results from the modulation of voltage-gated sodium channels in the context of epilepsy management?

    <p>Reduction of seizure propagation.</p> Signup and view all the answers

    Which statement regarding the structure of voltage-gated sodium channels is correct?

    <p>The alpha-subunit features four domains, each containing six transmembrane segments.</p> Signup and view all the answers

    What is the primary mechanism of action of Lamotrigine in controlling seizures?

    <p>Blocking sodium influx during seizure activity</p> Signup and view all the answers

    Which voltage-gated sodium channel is primarily associated with the antiseizure effects of Rufinamide?

    <p>Nav1.1</p> Signup and view all the answers

    Which of the following channels is implicated in epilepsy?

    <p>Nav1.2</p> Signup and view all the answers

    How do Phenytoin and Carbamazepine primarily exert their effects during seizures?

    <p>By prolonging the inactivated state of sodium channels</p> Signup and view all the answers

    What role do voltage-gated sodium channels play in the nervous system?

    <p>They are critical for neuronal excitability and signal propagation</p> Signup and view all the answers

    Which of the following medications specifically inhibits T-type calcium channels?

    <p>Ethosuximide</p> Signup and view all the answers

    What type of voltage-gated calcium channels are categorized as HVA?

    <p>Both B and C</p> Signup and view all the answers

    Gabapentin and Pregabalin primarily bind to which subunit of voltage-gated calcium channels?

    <p>α2δ</p> Signup and view all the answers

    Which of the following is NOT a high voltage-activated (HVA) calcium channel?

    <p>Cav3.2</p> Signup and view all the answers

    What is the role of voltage-gated calcium channels in the nervous system?

    <p>They facilitate neurotransmitter release.</p> Signup and view all the answers

    Which type of calcium channel is specifically identified as low voltage-activated?

    <p>Cav3.1</p> Signup and view all the answers

    Which calcium channel is recognized as the N-type involved in neuronal calcium signaling?

    <p>Cav2.2</p> Signup and view all the answers

    What is the primary effect of gabapentinoids on calcium channels?

    <p>Their effect on calcium influx is unclear.</p> Signup and view all the answers

    Which drug is specifically known to inhibit T-type calcium channels?

    <p>Ethosuximide</p> Signup and view all the answers

    What category do the voltage-gated calcium channels Cav3.1 to Cav3.3 fall into?

    <p>Low Voltage-Activated (LVA)</p> Signup and view all the answers

    Which condition is primarily characterized by chronic nerve pain and can be effectively treated with pregabalin?

    <p>Diabetic Peripheral Neuropathy</p> Signup and view all the answers

    Which mechanism is NOT part of pregabalin's action in pain relief?

    <p>Enhancing the release of substance P</p> Signup and view all the answers

    What is the primary target of pregabalin in modulating pain?

    <p>Voltage-gated calcium channels</p> Signup and view all the answers

    Which side effect is commonly associated with the use of pregabalin?

    <p>Increased appetite</p> Signup and view all the answers

    Which neurotransmitter release is directly inhibited by pregabalin during its action?

    <p>Glutamate</p> Signup and view all the answers

    In which type of pain is pregabalin particularly effective?

    <p>Chronic neuropathic pain</p> Signup and view all the answers

    What type of calcium channel does pregabalin primarily target to exert its effects?

    <p>T-type</p> Signup and view all the answers

    Which mechanism does pregabalin NOT utilize for pain management?

    <p>Enhancement of opioid receptor activity</p> Signup and view all the answers

    Which pain condition is primarily treated with pregabalin?

    <p>Migraine Pain</p> Signup and view all the answers

    What is the primary mechanism of action of pregabalin in managing neuropathic pain?

    <p>Binding to the α2δ subunit of voltage-gated calcium channels</p> Signup and view all the answers

    Which pain type is NOT commonly treated with pregabalin?

    <p>Osteoporosis Pain</p> Signup and view all the answers

    What role do NMDA receptors play that relates to pregabalin's action in pain perception?

    <p>They are involved in synaptic plasticity and chronic pain development.</p> Signup and view all the answers

    Which component interacts with pregabalin to modulate excitatory neurotransmitter release?

    <p>Calcium channel subunit α-neurexins</p> Signup and view all the answers

    What is the function of GABA-A receptors related to pregabalin's mechanism?

    <p>They enhance inhibitory neurotransmission in the CNS.</p> Signup and view all the answers

    Which type of calcium channel is primarily targeted by ethosuximide?

    <p>T-type (Transient)</p> Signup and view all the answers

    What is the significance of thrombospondins in pain management?

    <p>They are involved in the formation and maintenance of synaptic connections.</p> Signup and view all the answers

    What type of ion channel is the GABAA receptor?

    <p>Chloride ion channel</p> Signup and view all the answers

    What is the primary effect of GABAA receptor activation on a neuron?

    <p>Hyperpolarization of the neuron</p> Signup and view all the answers

    Which of the following substances does NOT interact with the GABAA receptor?

    <p>Opioids</p> Signup and view all the answers

    In which part of the body are GABAA receptors mainly found?

    <p>Central nervous system</p> Signup and view all the answers

    How do benzodiazepines affect the activity of GABAA receptors?

    <p>They enhance the receptor's response to GABA.</p> Signup and view all the answers

    What is a significant effect associated with barbiturates binding to the GABAA receptor?

    <p>Prolongation of GABA-induced chloride ion influx</p> Signup and view all the answers

    What type of response do GABAA receptors mediate when activated?

    <p>Fast inhibitory response</p> Signup and view all the answers

    Which substance is known to enhance the effects of GABA at the GABAA receptor?

    <p>Ethanol</p> Signup and view all the answers

    Which statement accurately describes the composition of GABAA receptors?

    <p>They consist of multiple subunits.</p> Signup and view all the answers

    What is the main role of GABAA receptors in the central nervous system?

    <p>To mediate inhibitory neurotransmission.</p> Signup and view all the answers

    When GABAA receptors are activated by GABA, what occurs?

    <p>Chloride ions flow into the cell.</p> Signup and view all the answers

    Benzodiazepines are primarily classified as which type of medication?

    <p>Anxiolytics</p> Signup and view all the answers

    What effect does GABAA receptor activation have on neuronal excitability?

    <p>It decreases neuronal excitability.</p> Signup and view all the answers

    Which agent is known to act as an antagonist of GABAA receptors?

    <p>Flumazenil</p> Signup and view all the answers

    How do barbiturates enhance the function of GABAA receptors?

    <p>By increasing the duration of chloride ion influx.</p> Signup and view all the answers

    Which ion primarily flows through the GABAA receptor when it is activated?

    <p>Chloride (Cl-)</p> Signup and view all the answers

    What type of assembly is the GABAA receptor?

    <p>Pentameric</p> Signup and view all the answers

    Which subunits are essential for GABA binding to the GABAA receptor?

    <p>α and β</p> Signup and view all the answers

    What is the main effect of benzodiazepines on the GABAA receptor?

    <p>They increase the frequency of channel opening.</p> Signup and view all the answers

    Which alcohol-related effect on GABAA receptors is associated with acute consumption?

    <p>Increased affinity of GABA for the receptor</p> Signup and view all the answers

    Which neuroactive substances are known to affect GABAA receptors?

    <p>All of the above</p> Signup and view all the answers

    What effect does phenobarbital have on GABAA receptor function?

    <p>It increases the duration of channel opening.</p> Signup and view all the answers

    How does tolerance to benzodiazepines develop with prolonged use?

    <p>Decreased receptor expression</p> Signup and view all the answers

    Which subunits are required for benzodiazepine binding to the GABAA receptor?

    <p>α and γ</p> Signup and view all the answers

    Which ligand is known to bind to the GABAA receptor and act as an agonist?

    <p>Muscimol</p> Signup and view all the answers

    What ion primarily flows through the GABAA receptor channel upon activation?

    <p>Chloride (Cl-)</p> Signup and view all the answers

    Which specific subunit composition of the GABAA receptor is linked with anxiolytic effects?

    <p>α1β2γ2</p> Signup and view all the answers

    What mechanism do barbiturates use to modify GABAA receptor activity?

    <p>They increase the duration of the channel opening.</p> Signup and view all the answers

    Which GABAA receptor subunit is least likely to be involved in benzodiazepine binding?

    <p>δ</p> Signup and view all the answers

    How does chronic alcohol consumption affect the GABAA receptors in the brain?

    <p>It reduces the number of GABAA receptors.</p> Signup and view all the answers

    What classification does the GABAA receptor fall under?

    <p>Ionotropic receptor</p> Signup and view all the answers

    Which condition could worsen following the withdrawal of benzodiazepines due to their involvement with GABAA receptors?

    <p>All of the above</p> Signup and view all the answers

    What is the primary function of the GABA A receptor?

    <p>To mediate inhibitory neurotransmission</p> Signup and view all the answers

    What is the typical number of subunits that compose the GABA A receptor?

    <p>Five</p> Signup and view all the answers

    Which subunit combination is required for GABA binding to the GABA A receptor?

    <p>α and β subunits</p> Signup and view all the answers

    What type of ions primarily flow through the GABA A receptor upon activation?

    <p>Chloride (Cl⁻)</p> Signup and view all the answers

    What effect do benzodiazepines have on the GABA A receptor?

    <p>They increase the frequency of channel opening in the presence of GABA.</p> Signup and view all the answers

    Where is the benzodiazepine binding site located on the GABA A receptor?

    <p>At the α-γ interface</p> Signup and view all the answers

    Which of the following is an allosteric modulator of the GABA A receptor?

    <p>Ethanol</p> Signup and view all the answers

    What is the role of the α subunit in the GABA A receptor?

    <p>It determines the receptor's sensitivity to benzodiazepines.</p> Signup and view all the answers

    What is the primary action of Vigabatrin?

    <p>It irreversibly inhibits mitochondrial GABA-transaminase.</p> Signup and view all the answers

    Which compound is primarily recognized for blocking GABA transporters?

    <p>Tiagabine</p> Signup and view all the answers

    What distinguishes Gabapentin's mechanism of action from that of GABA?

    <p>Gabapentin does not bind to GABA receptors.</p> Signup and view all the answers

    How does Valproate primarily influence GABA levels in the brain?

    <p>It inhibits GABA transaminase.</p> Signup and view all the answers

    Which of the following accurately describes the role of Tiagabine in GABAergic signaling?

    <p>It blocks the uptake of GABA from the synaptic cleft.</p> Signup and view all the answers

    What action does darigabat selectively target in GABA receptors?

    <p>It acts on GABA A receptor subtypes α2/3/5.</p> Signup and view all the answers

    Which drug is an irreversible inhibitor of GABA transaminase?

    <p>Vigabatrin</p> Signup and view all the answers

    What is the mechanism of action for cenobamate?

    <p>It modulates both GABA and glutamate signaling.</p> Signup and view all the answers

    What is the primary role of glutamate in the brain?

    <p>It serves as the principal excitatory neurotransmitter.</p> Signup and view all the answers

    Which of the following glutamate receptors is NOT classified as a type of receptor?

    <p>GABA</p> Signup and view all the answers

    What permeable ions are associated with NMDA receptors?

    <p>Na+ and Ca2+</p> Signup and view all the answers

    Which drug is recognized for its ability to block AMPA receptors?

    <p>Perampanel</p> Signup and view all the answers

    What is the mechanism of action of topiramate in relation to glutamate?

    <p>It acts as a glutamate antagonist at kainate receptors.</p> Signup and view all the answers

    What is the primary role of glutamate transporters in the nervous system?

    <p>They facilitate the reuptake of glutamate into presynaptic neurons and glial cells.</p> Signup and view all the answers

    Which statement accurately describes the effect of AMPA and kainate receptors on neurons?

    <p>They mediate fast excitatory synaptic transmission.</p> Signup and view all the answers

    Which receptor subunit does not belong to the NMDA receptor complex?

    <p>GluK1</p> Signup and view all the answers

    In pharmacology, how is glutamate classified in terms of its action at receptors?

    <p>It is classified as an excitatory neurotransmitter.</p> Signup and view all the answers

    What characteristic is essential for NMDA receptors to function properly?

    <p>They require glycine as a co-agonist.</p> Signup and view all the answers

    In the context of epilepsy treatment, what is the primary purpose of drugs targeting glutamate receptors?

    <p>To diminish excitatory neurotransmission and prevent seizures.</p> Signup and view all the answers

    What serious side effect is commonly associated with drugs that act on glutamate receptors?

    <p>Neurotoxicity.</p> Signup and view all the answers

    How does perampanel influence AMPA receptors?

    <p>It inhibits the receptors' function.</p> Signup and view all the answers

    Which drug is known to indirectly enhance AMPA receptor activity?

    <p>Positive allosteric modulators of AMPA receptors</p> Signup and view all the answers

    What is the primary action of felbamate on glutamate receptors?

    <p>It inhibits AMPA receptor function.</p> Signup and view all the answers

    Which drug selectively inhibits T-type calcium channels?

    <p>Ethosuximide</p> Signup and view all the answers

    Which common side effect is associated with NMDA receptor antagonists?

    <p>Cognitive impairment</p> Signup and view all the answers

    How does pregabalin act on calcium channels?

    <p>It inhibits the α2δ subunit of voltage-gated calcium channels.</p> Signup and view all the answers

    What is the mechanism of action of topiramate regarding glutamate?

    <p>It inhibits Kainate receptors and reduces glutamate release.</p> Signup and view all the answers

    Which of the following drugs is considered not typically classified as an anticonvulsant?

    <p>Ketamine</p> Signup and view all the answers

    Which drug increases GABA levels by inhibiting GABA transaminase?

    <p>Vigabatrin</p> Signup and view all the answers

    What is the primary function of Synaptic Vesicle Protein 2A (SV2A)?

    <p>Enhances neurotransmitter release</p> Signup and view all the answers

    Which drug is known to bind to SV2A and decrease glutamate release?

    <p>Levetiracetam</p> Signup and view all the answers

    In which process is SV2A primarily involved?

    <p>Synaptic vesicle recycling</p> Signup and view all the answers

    What effect does levetiracetam have on SV2A function?

    <p>It binds to SV2A to modulate glutamate release.</p> Signup and view all the answers

    Which of the following options is NOT a characteristic of SV2A?

    <p>It is involved in neurotransmitter uptake.</p> Signup and view all the answers

    What role does synaptotagmin serve in neurotransmitter release?

    <p>It serves as a calcium sensor.</p> Signup and view all the answers

    Which neurotransmitter is primarily associated with SV2A and glutamate receptors?

    <p>Glutamate</p> Signup and view all the answers

    What happens to SV2A and VGLUT co-expression in responders to levetiracetam?

    <p>It is maintained adequately.</p> Signup and view all the answers

    What is the primary function of Synaptic Vesicle Protein 2A (SV2A)?

    <p>Enhances neurotransmitter release</p> Signup and view all the answers

    Which drug decreases glutamate release by binding to SV2A?

    <p>Levetiracetam</p> Signup and view all the answers

    SV2A plays a significant role in which of the following processes?

    <p>Synaptic vesicle recycling</p> Signup and view all the answers

    How does levetiracetam affect SV2A?

    <p>It binds to SV2A to modulate glutamate release.</p> Signup and view all the answers

    Which characteristic is NOT associated with SV2A?

    <p>It is involved in neurotransmitter uptake.</p> Signup and view all the answers

    What role does synaptotagmin have in neurotransmitter release?

    <p>It serves as a calcium sensor.</p> Signup and view all the answers

    Which neurotransmitter is primarily associated with SV2A and glutamate receptors?

    <p>Glutamate</p> Signup and view all the answers

    What happens to the co-expression of SV2A and VGLUT in responders to levetiracetam?

    <p>It is maintained adequately.</p> Signup and view all the answers

    Which antiseizure medication is most likely to cause weight gain?

    <p>Valproate</p> Signup and view all the answers

    Which medication is classified as a hepatic enzyme inducer?

    <p>Carbamazepine</p> Signup and view all the answers

    What is the primary route of excretion for Gabapentin?

    <p>Renal excretion</p> Signup and view all the answers

    Which antiseizure medication should young women avoid due to teratogenic risk?

    <p>Valproate</p> Signup and view all the answers

    Which of the following is recognized as a second-generation antiseizure medication?

    <p>Levetiracetam</p> Signup and view all the answers

    Regarding cluster seizures, which statement is accurate?

    <p>Rectal diazepam gel can be administered for immediate relief.</p> Signup and view all the answers

    Developmental toxicology studies concentrate on which aspect?

    <p>Abnormal development following exposure to harmful agents</p> Signup and view all the answers

    Which study assesses the potential effects on embryo-foetal survival and morphological development?

    <p>Reproductive toxicology study</p> Signup and view all the answers

    Which study primarily focuses on maternal toxicity and its effects on embryonic and fetal survival?

    <p>Embryo-Foetal Development (EFD) Study</p> Signup and view all the answers

    Which antiseizure medication enhances GABA receptor activity while also inhibiting sodium channels?

    <p>Cenobamate</p> Signup and view all the answers

    What is the term used to describe the study of non-heritable birth defects?

    <p>Teratology</p> Signup and view all the answers

    Which antiseizure medication primarily works by enhancing GABAergic activity?

    <p>Phenobarbital</p> Signup and view all the answers

    What is the major metabolic pathway involved in the metabolism of phenytoin?

    <p>Cytochrome P450 metabolism</p> Signup and view all the answers

    Which antiseizure medication is specifically indicated for absence seizures?

    <p>Ethosuximide</p> Signup and view all the answers

    What is the most common side effect associated with Lamotrigine?

    <p>Skin rash</p> Signup and view all the answers

    Which antiseizure medication is known for having significant drug-drug interaction potential?

    <p>Carbamazepine</p> Signup and view all the answers

    What is the primary mechanism of action of Valproate?

    <p>GABA enhancement and inhibition of glutamate</p> Signup and view all the answers

    Which antiseizure medication is considered the safest for women of childbearing age in terms of teratogenic effects?

    <p>Lamotrigine</p> Signup and view all the answers

    What is the primary use of benzodiazepines in clinical practice?

    <p>Generalized anxiety disorder</p> Signup and view all the answers

    Which medications are commonly used for migraine prophylaxis?

    <p>Valproate and Topiramate</p> Signup and view all the answers

    In the context of seizure management, what is the primary goal of polypharmacy?

    <p>To maximize the effect of each individual agent</p> Signup and view all the answers

    What are the mechanisms of action for Felbamate?

    <p>Inhibiting sodium channels and enhancing GABA activity</p> Signup and view all the answers

    What is a common misconception about the use of polypharmacy in treating seizures?

    <p>It reduces the effectiveness of individual medications</p> Signup and view all the answers

    What does polypharmacy imply in the context of antiseizure medications?

    <p>The use of multiple agents to control seizures</p> Signup and view all the answers

    Which statement about polypharmacology is accurate?

    <p>It involves drugs with multiple pharmacological targets</p> Signup and view all the answers

    Which antiseizure medication is known for both inhibiting sodium channels and enhancing GABA receptor activity?

    <p>Cenobamate</p> Signup and view all the answers

    What additional function does Topiramate serve beyond inhibiting sodium channels?

    <p>It is an AMPA/kainate receptor antagonist</p> Signup and view all the answers

    Which of the following is a reported common use for Gabapentanoids besides seizure management?

    <p>Trigeminal neuralgia</p> Signup and view all the answers

    Which antiseizure medication is clinically indicated for bipolar disorder management?

    <p>Valproate</p> Signup and view all the answers

    What characterizes the concept of polypharmacy within antiseizure therapy?

    <p>The use of several drugs to work synergistically</p> Signup and view all the answers

    How does Cenobamate enhance its effectiveness in seizure control?

    <p>By inhibiting sodium channels and enhancing GABA activity</p> Signup and view all the answers

    What is the main goal of the Pre- and Post-natal Development (PPND) study?

    <p>Assess pre- and postnatal viability of offspring</p> Signup and view all the answers

    During which gestational days are rodents dosed in the Embryo-Foetal Development (EFD) studies?

    <p>Days 6-17</p> Signup and view all the answers

    What type of analyses are performed during Caesarean sections in the PPND study?

    <p>Health assessment of offspring and necroscopy</p> Signup and view all the answers

    What parameter is measured to assess embryo-foetal survival in the EFD studies?

    <p>Foetal morphology</p> Signup and view all the answers

    How many animals are typically used per sex per group in the Fertility and Early Embryonic Development (FEED) study?

    <p>16</p> Signup and view all the answers

    What specific aspect of maternal health does the EFD study compare?

    <p>Maternal toxicity compared to non-pregnant females</p> Signup and view all the answers

    What is the significance of caesarean sections performed on day 20 in EFD studies?

    <p>To assess foetal development close to term</p> Signup and view all the answers

    What is a key consideration when dosing females in the PPND study?

    <p>Dosing ranges from gestational day 6 to post-natal day 20</p> Signup and view all the answers

    What is the main focus of developmental toxicology?

    <p>Study of pharmacokinetics and mechanisms of abnormal development</p> Signup and view all the answers

    Which of the following factors influences the effect of a teratogen on development?

    <p>Extent of transfer to the foetus</p> Signup and view all the answers

    What is the purpose of genotoxicity studies in the context of drug testing?

    <p>To determine if there is a potential for genetic damage</p> Signup and view all the answers

    What does the 'Segment I' study in Development and Reproductive Toxicity (DART) involve?

    <p>Evaluation of fertility and early embryonic development</p> Signup and view all the answers

    Which animal is commonly used in teratogenicity studies according to DART guidelines?

    <p>Rat</p> Signup and view all the answers

    What is the primary aim of Development and Reproductive Toxicity (DART) studies?

    <p>To minimize costs and animal use in experiments</p> Signup and view all the answers

    What role do non-human primates play in DART studies?

    <p>They are only considered in special cases</p> Signup and view all the answers

    How many tests are included in the standard genotoxicity battery?

    <p>Three</p> Signup and view all the answers

    Study Notes

    Seizure Types

    • Generalized Tonic-Clonic Seizure: Characterized by a staring spell, followed by rhythmic jerking of arms and legs, loss of consciousness, post-ictal confusion, and possible tongue biting and urinary incontinence.
    • Absence Seizures: Brief loss of awareness, blank stare, no postictal confusion, and occurs multiple times a day.
    • Focal Onset Seizures: Usually have a specific part of the brain that is affected, can be either aware or impaired awareness. Impaired awareness may present with confusion and disorientation.
    • Atonic Seizures: Sudden muscle weakness causing falls, with no loss of consciousness, lasting only a few seconds.
    • Myoclonic Seizures: Sudden jerking of muscles, typically in the arms and legs, can occur in clusters or independently.
    • Complex Partial Seizures: Muscle stiffness followed by jerking movements, often preceded by a warning sign, and post-ictal exhaustion.
    • Simple Partial Seizures: May or may not include loss of consciousness.
    • Benign Febrile Seizures: Typically occur in children under the age of 5, often triggered by fever and do not typically lead to epilepsy.

    Seizure Management

    • Intravenous Benzodiazepines: Immediate management of prolonged seizures lasting over 10 minutes.
    • Antiepileptic Medications: Used to prevent seizures, and the dose may need to be adjusted based on seizure frequency.
    • EEG: Electroencephalogram, often a helpful tool for diagnosing seizures, especially in children experiencing shaking and falling.
    • MRI: Magnetic Resonance Imaging, used to rule out structural problems in the brain, especially in individuals with a suggestive history of epilepsy or new seizures.
    • Driving Restrictions: When a person has had a seizure they must stop driving for 6 months after their last seizure, and only after being evaluated and cleared by a doctor.

    Seizure Triggers

    • Stress: Increased stress can be a factor in the frequency of seizures.
    • Dehydration: Can trigger prolonged seizures, especially in children.
    • Alcohol Withdrawal: Can trigger seizures in individuals with a history of alcohol dependence.
    • Hypoglycemia: Low blood sugar can trigger seizures, especially in individuals with diabetes.
    • Substances: Certain substances like illicit drugs and alcohol can trigger seizures.

    Underlying Causes

    • Possible causes of seizures include:
      • Subdural Hematoma: Often seen in elderly patients, especially after a fall.
      • Primary Generalized Epilepsy: A type of epilepsy where seizures originate in both hemispheres of the brain.
    • Brain Tumor: Can cause seizures, especially in adults.
    • Underlying Medical Conditions: Certain medical conditions can increase the risk of seizures, including diabetes, heart disease, and stroke.

    Important Considerations

    • Regularly prescribed medication: Following the schedule for anti-epileptic medication can reduce the risk of seizures.
    • Consult a neurologist: For accurate diagnosis and management of seizures.
    • Avoid driving until cleared: This prevents potential accidents and ensures safety.
    • Reduce stress: Stress can trigger seizures.
    • Evaluate for underlying causes: A thorough evaluation for heart problems, diabetes, and stroke will rule out co-morbidities.

    Deciding to Start Antiseizure Medication (ASM) After a First Unprovoked Seizure

    • Primary consideration: The presence of underlying causes
    • Example: Tumors
    • ASM reduces risk of subsequent seizures: 35%
    • Long-term quality of life: No difference between immediate and deferred treatment
    • High-risk factors for seizure recurrence:
      • Epileptiform abnormalities on interictal EEG
      • First seizure during sleep
      • Remote symptomatic causes identified by imaging

    Epilepsy Diagnosis

    • Diagnosis Criteria: Two unprovoked seizures occurring more than 24 hours apart

    Risk and Treatment

    • Cumulative risk of seizure recurrence within 10 years with structural lesions: 26%
    • ASM generally suggested: When there is evidence of high risk for recurrent seizures

    Voltage-Gated Sodium Channels (Nav)

    • The Nav gene family comprises nine members: Nav1.1 to Nav1.9.
    • Each Nav channel consists of a single alpha-subunit with four domains, each containing six transmembrane segments.
    • Nav channels can associate with beta-subunits.
    • Play essential roles in the central nervous system (CNS), heart, and gut.
    • Nav1.1, Nav1.2, Nav1.3, and Nav1.6 are linked to epilepsy.

    Antiseizure Medications (ASMs) and Nav Channels

    • Lamotrigine, Phenytoin, and Carbamazepine bind to Nav1.2 channels in their fast inactivated state, slowing channel recovery and reducing sodium influx.
    • This blockade primarily occurs during seizure activity.
    • Lamotrigine also decreases calcium currents and glutamate release, further contributing to seizure control.
    • Rufinamide targets Nav1.1 and Nav1.6, contributing to its antiseizure effects.

    Clinical Relevance

    • Modulating voltage-gated sodium channels is crucial for epilepsy management.
    • This modulation reduces neuronal excitability and inhibits seizure propagation.

    Voltage-Gated Sodium Channels (Nav)

    • The Nav gene family comprises nine members (Nav1.1 to Nav1.9).
    • Each Nav channel is composed of a single alpha-subunit with four domains.
    • Each domain contains six transmembrane segments.
    • Nav channels can associate with beta-subunits.
    • Nav channels play a role in various physiological functions in the CNS, heart, and gut.
    • Nav1.1, Nav1.2, Nav1.3, and Nav1.6 are linked to epilepsy.

    Antiseizure Medications (ASMs)

    • Lamotrigine, Phenytoin, and Carbamazepine bind to Nav1.2 channels in their fast inactivated state.
    • This binding slows the recovery of the channel, reducing sodium influx.
    • The blockade of these channels is primarily observed during seizure activity.
    • Lamotrigine also reduces calcium currents and glutamate release, further contributing to its anti-seizure effects.
    • Rufinamide acts on Nav1.1 and Nav1.6 channels, contributing to its anti-seizure effects.

    Clinical Significance

    • Modulation of Nav channels is crucial for managing epilepsy.
    • This modulation helps reduce neuronal excitability and prevent seizure propagation.

    Voltage-Gated Calcium Channels (Cav)

    • Cav channels are similar in structure to voltage-gated sodium channels (Nav).
    • There are 10 different types of Cav channels.

    High Voltage-Activated (HVA) Channels

    • L-type: Cav1.1 - 1.4
    • P-type: Cav2.1
    • N-type: Cav2.2
    • R-type: Cav2.3

    Low Voltage-Activated (LVA) Channels

    • T-type: Cav3.1 - 3.3

    Cav Channel Categorization

    • High Voltage-Activated (HVA)
    • Intermediate Voltage-Activated (IVA)
    • Low Voltage-Activated (LVA)

    Cav Channel Targeting

    • Ethosuximide: Inhibits T-type calcium channels (Cav3.1-3.3).
      • Important in treating absence seizures.
    • Gabapentinoids (Pregabalin and Gabapentin): Bind to the α2δ subunit of high-voltage calcium channel accessory proteins.
      • Effect on calcium influx is unclear.
      • Used for their analgesic and anticonvulsant properties.

    Clinical Significance

    • Modulating Cav channels is crucial for treating various seizure types.
    • Cav channels play a significant role in neurotransmitter release and neuronal signaling.

    Pregabalin

    • Primary Use: Primarily used for managing migraine pain.
    • Mechanism of Action: Works by binding to the α2δ subunit of voltage-gated calcium channels.
    • Pain Types Not Typically Treated: Osteoporosis pain is not commonly treated with pregabalin.
    • NMDA Receptors and Pain: NMDA receptors are involved in synaptic plasticity and chronic pain development.
    • Interaction with Calcium Channel Subunit: Pregabalin interacts with calcium channel subunit α-neurexins to modulate excitatory neurotransmitter release.
    • GABA-A Receptors: Pregabalin acts indirectly by enhancing GABA-A receptor activity, which promotes inhibitory neurotransmission in the CNS.
    • Effect on Glutamate Release: Pregabalin reduces the release of glutamate, a crucial excitatory neurotransmitter in pain signaling.
    • Conditions with Significant Prion Protein Involvement: Diabetic peripheral neuropathy is a condition where prion proteins play a significant role.
    • Common Side Effects: Increased appetite is a potential side effect of pregabalin.

    Other Relevant Information

    • Ethosuximide Target: Ethosuximide primarily targets T-type (transient) calcium channels.
    • Thrombospondins and Synaptic Connections: Thrombospondins are involved in the formation and maintenance of synaptic connections, crucial for pain perception.
    • Fibromyalgia: This condition, characterized by widespread musculoskeletal pain, is often treated with pregabalin.
    • Mechanism of Action in Pain Relief: Pregabalin primarily reduces synaptic excitability by inhibiting calcium channels.
    • Indications for Use: Pregabalin is indicated for treating chronic neuropathic pain.
    • Advantages of Pregabalin in Pain Management: Pregabalin possesses a unique advantage over other pain medications due to its applicability in both acute and chronic pain management.
    • Calcium Channel Target: Pregabalin primarily targets T-type calcium channels.
    • Effectiveness in Diabetic Peripheral Neuropathy: Pregabalin's effectiveness in treating diabetic peripheral neuropathy arises from its action on voltage-gated calcium channels.
    • Neuropathic Pain Condition: Postherpetic neuralgia is a neuropathic pain condition effectively treated by pregabalin.

    GABAA Receptor

    • The GABAA receptor is a chloride ion channel.
    • Activation of the GABAA receptor causes hyperpolarization of the neuron, which inhibits neuronal firing.
    • The primary neurotransmitter that activates the GABAA receptor is GABA.
    • Ligands that bind to the GABAA receptor include:
      • GABA
      • Benzodiazepines
      • Barbiturates
    • Opioids do not bind to the GABAA receptor.

    Location and Function

    • GABAA receptors are primarily located in the central nervous system.
    • They mediate inhibitory neurotransmission.
    • The effect of GABAA receptor activation is a fast inhibitory response.

    Modulation of Activity

    • Ethanol enhances the effect of GABA at the GABAA receptor.
    • Benzodiazepines enhance the receptor's response to GABA.
    • Barbiturates prolong GABA-induced chloride ion influx.

    GABAA Receptors

    • Are composed of multiple subunits
    • Mediate inhibitory neurotransmission in the brain
    • Open and allow chloride ions to flow in when GABA binds
    • Decreases neuronal excitability
    • Targeted by medications for anxiety disorders
    • Activation by GABA produces an anxiolytic effect

    Pharmacology of GABAA Receptors

    • Benzodiazepines are anxiolytics that enhance GABAA receptor function
    • Barbiturates enhance GABAA receptor function by binding to a different site and increasing chloride influx duration
    • Flumazenil is an antagonist of GABAA receptors

    GABAA Receptor Structure and Function

    • The GABAA receptor is a pentameric assembly.
    • The α and β subunits are essential for GABA binding.
    • The α and γ subunits are required for benzodiazepine binding.
    • Benzodiazepines increase the frequency of channel opening, potentiating the effects of GABA.
    • Phenobarbital increases the duration of channel opening, enhancing GABA's inhibitory effects.

    GABAA Receptor Antagonists and Modulators

    • Bicuculline is a known GABAA receptor antagonist.
    • Acute alcohol consumption increases the affinity of GABA for the receptor.
    • Prolonged benzodiazepine use leads to decreased receptor expression, contributing to tolerance.

    GABAA Receptor and Chloride Ions

    • Chloride ions are essential for the inhibitory response of the GABAA receptor.

    GABAA Receptor Interactions with Neuroactive Substances

    • Steroids, alcohols, and anesthetics are known to affect GABAA receptors.

    GABAA Receptor Agonists and Antagonists

    • Muscimol is an agonist of the GABAA receptor.

    • Flumazenil, Picrotoxin, and Ro15-4513 are antagonists of the GABAA receptor.

    Ion Flow Through GABAA Receptor Channel

    • The primary ion that flows through the GABAA receptor channel upon activation is chloride (Cl-).

    GABAA Receptor Subunit Composition and Function

    • The α1β2γ2 subunit composition of the GABAA receptor is primarily associated with anxiolytic effects.

    • The δ subunit is not typically involved in the binding of benzodiazepines.

    Modulation of GABAA Receptor Activity

    • Barbiturates increase the duration of the channel opening, enhancing GABAA receptor activity.

    Chronic Alcohol Consumption and GABAA Receptors

    • Chronic alcohol consumption reduces the number of GABAA receptors, leading to decreased sensitivity to GABA.

    GABAA Receptor Classification

    • The GABAA receptor is classified as an ionotropic receptor.

    Benzodiazepine Withdrawal and GABAA Receptors

    • Withdrawal from benzodiazepines can exacerbate epilepsy, depression, and anxiety disorders due to their effects on GABAA receptors.

    Beta Subunit of GABAA Receptors

    • The β subunit of the GABAA receptor regulates the opening of the ion channel.

    Flumazenil and Benzodiazepine Overdose

    • Flumazenil is a GABAA receptor antagonist commonly used in the treatment of benzodiazepine overdose.

    GABAA Receptor Function

    • The GABAA receptor is a ligand-gated ion channel that mediates inhibitory neurotransmission.
    • GABAA receptors are composed of five subunits
    • The α and β subunits are responsible for GABA binding.
    • Chloride ions primarily flow through the GABAA receptor upon activation, resulting in hyperpolarization of the neuron.
    • Benzodiazepines increase the frequency of channel opening in the presence of GABA, enhancing inhibitory neurotransmission.
    • The benzodiazepine binding site is located at the α-γ interface on the GABAA receptor.
    • Ethanol is an allosteric modulator of the GABAA receptor.
    • The α subunit determines the receptor's sensitivity to benzodiazepines.
    • Chronic alcohol exposure decreases the inhibitory sensitivity of the GABAA receptor.

    GABAergic Drugs

    • Vigabatrin irreversibly inhibits mitochondrial GABA-transaminase, preventing the breakdown of GABA.
    • Valproate inhibits GABA transaminase, leading to increased levels of GABA in the brain.
    • Tiagabine blocks the uptake of GABA from the synaptic cleft, increasing GABA's concentration in the synapse.
    • Gabapentin and pregabalin modulate voltage-gated calcium channels, which indirectly affects GABA release and neuronal excitability.

    GABA Receptor Modulation

    • Barbiturates act as allosteric modulators on GABA receptors, increasing the duration of channel opening and enhancing GABA's effects.
    • Darigabat is selective for GABAA receptor subtypes α2/3/5, providing targeted modulation.

    Other GABAergic Drugs

    • Cenobamate modulates both GABA and glutamate signaling.

    GABA vs. Gabapentin

    • Gabapentin does not bind to GABA receptors; its mechanism of action is independent of direct GABA receptor interactions.

    Glutamate

    • Glutamate is the primary excitatory neurotransmitter in the brain.

    Glutamate Receptors

    • There are four main types of glutamate receptors:
      • NMDA
      • AMPA
      • Kainate
      • GABA is not a glutamate receptor.

    NMDA Receptors

    • NMDA receptors are permeable to sodium (Na+) and calcium (Ca2+).

    AMPA Receptors

    • AMPA receptors are composed of four subunits: GluA1 - GluA4.

    AMPA Receptor Blockers

    • Perampanel blocks AMPA receptors.
    • Felbamate blocks AMPA receptors.

    Glutamate Receptor Structure

    • Glutamate receptors consist of four subunits.

    Topiramate and Glutamate

    • Topiramate acts as a glutamate antagonist at kainate receptors.

    Glutamate Transporters

    • Play a role in the reuptake of glutamate into presynaptic neurons and glial cells.

    AMPA and Kainate Receptors

    • Primarily mediate fast excitatory synaptic transmission.

    NMDA Receptors

    • GluK1 is not part of the NMDA receptor complex.
    • Require the presence of glycine as a co-agonist.

    Glutamate

    • Classified as an excitatory neurotransmitter.

    Glutamate Receptor Drugs

    • Target glutamate receptors for the treatment of epilepsy, anxiety disorders, and schizophrenia.
    • Common side effect is neurotoxicity.

    Perampanel

    • Blocks AMPA receptors.

    AMPA Receptor Activity

    • Enhanced indirectly by positive allosteric modulators of AMPA receptors.

    AMPA Receptor Antagonist

    • Perampanel is an AMPA receptor antagonist.

    Felbamate

    • Inhibits AMPA receptor function.

    Ethosuximide

    • Known for its selective inhibition of the T-type calcium channels.

    Topiramate

    • Inhibits Kainate receptors and reduces glutamate release.

    NMDA Receptor Antagonists

    • Common side effect is cognitive impairment.

    Vigabatrin

    • Increases GABA levels by inhibiting GABA transaminase.

    Riluzole

    • Primarily targets mGluR (metabotropic glutamate receptor).

    Anticonvulsants

    • Ketamine is not typically classified as an anticonvulsant.

    Pregabalin

    • Inhibits the α2δ subunit of voltage-gated calcium channels.

    Levetiracetam

    • Modulates glutamate activity and is used as an adjunct therapy for refractory epilepsy.

    Synaptic Vesicle Protein 2A (SV2A)

    • SV2A is a synaptic vesicle protein that enhances neurotransmitter release.
    • It is involved in synaptic vesicle recycling, the process of replenishing vesicles with neurotransmitters after release.
    • SV2A interacts with the drug levetiracetam, which binds to it and modulates glutamate release.
    • SV2A does not directly participate in neurotransmitter uptake.

    Levetiracetam

    • Levetiracetam is a medication that binds to SV2A and decreases glutamate release.
    • It has no effect on SV2A function, but its binding modulates glutamate release.

    Glutamate and SV2A

    • SV2A is associated with glutamate receptors, and the neurotransmitter glutamate is primarily involved in the interaction between SV2A and glutamate receptors.
    • Individuals who respond to levetiracetam therapy continue to have adequate co-expression of SV2A and VGLUT.

    Synaptotagmin

    • Synaptotagmin acts as a calcium sensor during neurotransmitter release.

    Other Medications and Mechanisms

    • Vigabatrin is a GABAergic agonist, meaning it increases the activity of GABA, a neurotransmitter that inhibits neuronal activity.
    • Gabapentin is a medication that does not directly act on glutamate receptors.
    • Topiramate and Felbamate are medications that interact with glutamate receptors.

    SV2A Function

    • SV2A is a protein primarily involved in the enhancement of neurotransmitter release.

    SV2A and Levetiracetam

    • Levetiracetam, an antiepileptic drug, binds to SV2A.
    • This binding inhibits the release of glutamate, a neurotransmitter.
    • Levetiracetam's action affects synaptic vesicle recycling, a process where SV2A is involved.

    SV2A Characteristics

    • SV2A is a synaptic vesicle protein but is not involved in neurotransmitter uptake.

    Synaptotagmin and Neurotransmitter Release

    • Synaptotagmin, another protein, plays a crucial role in neurotransmitter release by acting as a calcium sensor.

    SV2A, Glutamate, and Levetiracetam Response

    • SV2A is particularly related to glutamate, a neurotransmitter.
    • The co-expression of SV2A and vesicular glutamate transporter (VGLUT) remains stable in individuals who respond to levetiracetam.

    Drug Mechanisms of Action

    • Vigabatrin, an antiepileptic drug, is a GABAergic agonist, meaning it enhances the effects of GABA in the brain.
    • Gabapentin is a unique antiepileptic drug that does not directly act on glutamate receptors.

    Antiseizure Medications (ASM) - Key Facts

    • Valproate is associated with weight gain.
    • Carbamazepine is a potent inducer of hepatic enzymes.
    • Gabapentin is primarily excreted by the kidneys.
    • Valproate carries a higher teratogenic risk and is contraindicated in young women of childbearing age.
    • Levetiracetam is classified as a second-generation antiseizure medication.
    • Rectal diazepam gel can be used for immediate treatment of cluster seizures.
    • Developmental toxicology studies focus on abnormal development after exposure to agents.
    • The EFD (Embryo-Foetal Development) study assesses maternal toxicity and potential effects on embryo-foetal survival and development.
    • Cenobamate inhibits sodium channels and enhances GABA receptor activity, illustrating polypharmacology.
    • Teratology investigates non-heritable birth defects.

    ### ASM - Additional Key Facts

    • Phenobarbital is classified as a first-generation ASM and primarily works by enhancing GABAergic activity.
    • Phenytoin is primarily metabolized via the cytochrome P450 enzyme system in the liver.
    • Ethosuximide is specifically indicated for the treatment of absence seizures.
    • A common side effect of lamotrigine is skin rash, which can potentially progress to Stevens-Johnson syndrome.
    • Levetiracetam is often the first-line treatment for partial-onset seizures.
    • Carbamazepine has a high potential for drug-drug interactions due to its potent hepatic enzyme induction properties.
    • Valproate increases GABA levels and inhibits glutamate release, contributing to its antiseizure effects.
    • Topiramate is known to cause cognitive side effects, including memory impairments.
    • Kidney stones are more commonly associated with topiramate, not levetiracetam.
    • Lamotrigine is considered the safest option for women of childbearing age in terms of teratogenic effects.

    Antiseizure Medication & Polypharmacy

    • Polypharmacy refers to the use of multiple medications to control seizures
    • Polypharmacology involves using drugs that can interact with multiple targets, enhancing their therapeutic potential
    • Cenobamate inhibits sodium channels and enhances GABA receptor activity
    • Topiramate inhibits sodium channels, enhances GABA activity, and acts as an AMPA/kainate receptor antagonist
    • Gabapentanoids are commonly used to manage neuropathic pain, including trigeminal neuralgia
    • Valproate is indicated for the management of bipolar disorder in addition to its use in epilepsy
    • Benzodiazepines are commonly prescribed for the management of anxiety disorders, including generalized anxiety disorder
    • Both Valproate and Topiramate are utilized for migraine prophylaxis in addition to their roles as antiseizure medications
    • The goal of polypharmacy is to achieve synergistic effects and reduce the doses of individual medications while controlling seizures effectively
    • Felbamate inhibits sodium channels and enhances GABAergic activity

    Developmental toxicology

    • The study of how exposure to chemicals, agents, and conditions affect development.
    • Effects can be structural or non-structural.
    • Examples of non-structural effects: obesity, autism, diabetes.

    Teratology

    • The study of non-heritable birth defects, also known as congenital defects.
    • Teratogens are agents that cause birth defects.
    • Factors influencing the effect of teratogens:
      • Extent of transfer to the fetus.
      • Duration of exposure.
      • Timing of exposure.
      • Genetic susceptibility.

    Genotoxicity Studies

    • Required before first human exposure to assess the potential for genetic damage.
    • Standard 3-test battery:
      • Gene mutation test in bacteria.
      • In vitro chromosomal damage test in mammalian cells.
      • In vivo chromosomal damage test in rat hematopoietic cells.

    Development and Reproductive Toxicity (DART) Studies

    • Based on ICH S5(R3) guidelines.
    • Three types of studies:
      • Fertility and early embryonic development study (FEED).
      • Embryo-foetal development studies in two species (EFD).
      • Pre- and a postnatal development study (PPND).
    • Studies are performed only when needed to minimize cost and animal use.

    Study Design

    • Animal selection should reflect those used in toxicology studies.
    • Design based on TK/TD profile and AOP (adverse outcome pathway).
    • Typical species: rat; second non-rodent species: rabbit, in some cases a non-human primate might be used.

    Fertility and Early Embryonic Development (FEED) Study

    • Assess adverse effects from treatment initiated before mating, through mating and implantation.
    • 16 animals per sex per group, 4 doses (including placebo).
    • Males exposed to drug for 2-4 weeks before cohabitation until confirmed mating.
    • Females exposed to drug for 2-4 weeks before cohabitation until implantation.
    • Caesarean sections performed mid-gestation.
    • Sperm counts and oestrus cycle measurements can be performed prior to mating.

    Embryo-Foetal Development (EFD) studies

    • Assess maternal toxicity compared to non-pregnant females.
    • Evaluate effects on embryo-foetal survival, intrauterine growth, and morphological development.
    • 16 females per group, 4 doses (including placebo).
    • Rodents dosed from gestational day 6-17.
    • Caesarean sections performed on day 20.
    • Parameters measured:
      • Foetal morphology.
      • Foetal weight.
      • Uterine weight.

    Pre- and a Post-natal Development (PPND) Study

    • Assess enhanced toxicity relative to non-pregnant females.
    • Evaluate pre- and postnatal viability, altered growth and development, and functional deficits in offspring.
    • 16 litters, 4 doses (including placebo).
    • Exposure from gestational day 6 to post-natal day 20 (implantation to weaning).
    • Animals assessed for health and necroscopy performed.
    • 16 animals per sex/group studied until sexual maturity.
    • Animals mated, offspring assessed for health.

    Risk of Major Congenital Malformations Associated with Perinatal Antiseizure Medication Exposure

    • Perinatal exposure to antiseizure medication can increase risk of major congenital malformations.
    • ASM = antiseizure medication
    • VPA = valproate
    • LEV = levetiracetam
    • LTG = lamotrigine

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