61 Questions
Which drug competitively inhibits the voltage-gated sodium channel, preventing burst firing?
Lamotrigine
Which drug is highly effective in Absence epilepsy by blocking T-type calcium channels in the thalamus?
Ethosuximide
Which type of epilepsy is characterized by intermittent high amplitude discharges at the site of epileptic focus during inter-ictal periods?
Focal epilepsy
Which anticonvulsant drug facilitates GABAergic transmission and tends to cause drowsiness/sedation?
Levetiracetam
What is the impact of sodium valproate on cognitive development in infants?
It reduces IQ in infants by 9-10 points
Which enzyme does valproate inhibit?
CYP3A4
What is the percentage of refractory epilepsy patients who remain unresponsive to pharmacological treatment?
30-40%
Which group of patients face particular issues when starting epilepsy treatment?
Patients with intellectual disabilities
5
0
What is the most common side effect associated with long-term use of phenytoin?
Gingival hyperplasia
What percentage of patients with Juvenile Myoclonic Epilepsy are refractory to treatment?
20%
Which enzyme induction is associated with carbamazepine?
CYP450
What is the main issue concerning teratogenicity of anticonvulsants?
Anticonvulsants are implicated in congenital birth defects, especially sodium valproate
What issue might pharmacogenomics investigate in relation to variability in pharmacological success of AEDs?
Genetic differences among patients and drug targets such as sodium channels
What is the primary function of anti-epileptic drugs (AEDs) available today?
Prevent the spread of epileptic discharges
How do most anti-epileptic drugs (AEDs) work to prevent the spread of epileptic discharges?
By decreasing efficiency of inhibitory synaptic transmission – GABA
What is the aim of treatments for preventing increased activity in the brain attributable to increased membrane excitability?
To oppose these actions
Which type of drugs were the first generation antiepileptic drugs that act on reducing membrane excitability?
Sodium channel blockers and GABA enhancers
What is the primary action of sodium channel blockers in controlling seizures?
Block repetitive firing of neurons by acting at ion channels
What is the effect of drugs with selective actions at sodium channels on normal neuronal firing?
They do not impair normal neuronal firing
What is the impact of increased neuronal activity (as in a seizure) on neurons when inhibited by sodium channel blocker drugs?
It is inhibited, thereby preventing seizure spread
What is the primary function of GABA enhancers in reducing membrane excitability?
Increase efficiency of inhibitory synaptic transmission – GABA
What is the commonest form of primary generalized epilepsy?
Juvenile Myoclonic Epilepsy
What is the characteristic feature of Absence seizures?
Abrupt short episodes with unresponsiveness
Which type of seizures are characterized by electrical discharges starting in one cortical region and then may spread over the whole brain?
Partial/Focal Onset Seizures
What is the duration of a typical Generalized Tonic Clonic Seizure (Grand Mal)?
1-3 minutes
What is the main risk factor for Juvenile Myoclonic Epilepsy (JME)?
<15 years age at onset
What is the characteristic feature of Absences that distinguishes them from other seizure types?
<20 seconds duration with unresponsiveness
What is the most common type of seizure in patients with Juvenile Myoclonic Epilepsy (JME)?
Myoclonic Jerks
What is the characteristic feature of Complex Partial Seizures?
Aura/warning with reduced awareness
Which type of epilepsy is strongly associated with a space-occupying lesion?
Jacksonian march epilepsy
What type of seizures are often misdiagnosed as non-epileptic and have an often normal ictal EEG?
Frontal lobe seizures
Which symptom is typically associated with parietal lobe epilepsy?
Tingling and pain sensory symptoms
Which type of seizure is strongly associated with Todd's paresis?
Jacksonian march seizure
Which type of seizures are frequently predominantly nocturnal and have rapid recovery?
Frontal lobe seizures
Which type of seizure is characterized by a fencing posture, overlapping with temporal lobe epilepsy?
Temporal lobe seizure
Which type of seizure is characterized by oral automatisms like lip smacking and chewing movements?
Temporal lobe seizure
Which type of epilepsy symptom includes hallucinations of taste, speech, and/or smell, and visual distortion?
Temporal lobe epilepsy
Which type of seizure has a last duration of typically 1-3 minutes?
Temporal lobe seizure
Which type of sensory symptom is typically associated with occipital lobe epilepsy?
Visual hallucinations
What is the primary function of anti-epileptic drugs (AEDs) available today?
Reducing membrane excitability
What is the characteristic feature of Absence seizures?
Brief loss of awareness with rapid recovery
What is the impact of sodium valproate on cognitive development in infants?
Negative impact on cognitive development
Which type of epilepsy is characterized by intermittent high amplitude discharges at the site of epileptic focus during inter-ictal periods?
Temporal lobe epilepsy
What is the most common type of seizure in patients with Juvenile Myoclonic Epilepsy (JME)?
Myoclonic seizures
Which enzyme does valproate inhibit?
Histone deacetylases
What is the characteristic feature of Complex Partial Seizures?
Impaired consciousness with focal onset
What is the primary function of GABA enhancers in reducing membrane excitability?
Enhancing inhibitory neurotransmission
Which enzyme induction is associated with carbamazepine?
Cytochrome P450 enzymes
What is the impact of drugs with selective actions at sodium channels on normal neuronal firing?
Reduce normal neuronal firing
What is the aim of treatments for preventing increased activity in the brain attributable to increased membrane excitability?
Reduce membrane excitability
Which process is defined as the conversion of parts of a normal brain to a hyperexcitable brain?
Epileptogenesis
What is the physiological definition of an epileptic seizure?
An explosion of synchronous activity by lots of neurons at once
What tends to cause the 'electrical brain-storm' during an epileptic seizure?
Synchronous and rhythmic firing of action potentials by populations of neurons in the CNS
Why is the brain prone to seizure activity?
Conversion to a hyperexcitable state through epileptogenesis
What is the primary focus of ion channels in relation to epilepsy?
Channelopathies
What does EEG stand for in the context of epilepsy?
Electroencephalogram
What is the characteristic feature of an epileptic seizure?
Synchronous and rhythmic firing of action potentials by populations of neurons in the CNS
What is the impact of epileptogenesis on parts of a normal brain?
Conversion to a hyperexcitable state
What causes an 'electrical brain-storm' during an epileptic seizure?
Synchronous and rhythmic firing of action potentials by populations of neurons in the CNS
What does 'EEG' measure in relation to epilepsy?
Brain's electrical activity patterns
Study Notes
Antiepileptic Drugs and Their Mechanisms of Action
- Sodium channel blockers oldest to newest: Phenytoin, Carbamazepine (oxcarbazepine/ eslicarbazepine), Lamotrigine, Zonisamide, Lacosamide
- Sodium channel blockers prevent epileptiform discharges without affecting ordinary action potential firing
- Carbamazepine, oxcarbazepine, and eslicarbazepine competitively inhibit the voltage-gated sodium channel, preventing burst firing
- Several experimental agents active in animal models of epilepsy are blockers of NMDA, AMPA, or kainate subtypes of glutamate receptor
- Calcium channels are voltage-activated and regulate calcium entry and neurotransmitter release from pre-synaptic nerve terminals
- Ethosuximide, highly effective in Absence epilepsy, blocks T-type calcium channels in the thalamus
- Focal epilepsy is characterized by intermittent high amplitude discharges at the site of epileptic focus during inter-ictal periods
- Anticonvulsant drugs that facilitate GABAergic transmission tend to cause drowsiness/sedation
- Levetiracetam is a high-affinity synaptic vesicle protein-2A ligand that modulates neurotransmitter release and is effective in refractory epilepsy
- Relative rates of partial (focal) onset seizures reduction vs placebo: Levetiracetam – 3.81, Topiramate – 3.32, Lamotrigine – 2.71
- Choosing the right drug for the patient: ideal antiepileptic agent should have good efficacy, easy and rapid titration, no drug-drug interactions, and low side-effects
- Classification of seizures/epilepsy syndromes: Sodium valproate and lamotrigine are first-line for primary generalized epilepsy, while carbamazepine and lamotrigine are first-line for partial (focal onset) epilepsy. Some drugs exacerbate generalized seizure types.
Test your knowledge on the pharmacological treatments of epilepsy with a focus on anti-epileptic drugs (AEDs) and how they work. Explore the effectiveness of AEDs in preventing the spread of epileptic discharges and controlling seizures.
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