Pregunta 1
Pregunta
Epilepsy, the [blank_start]4th[blank_end] most common neurological disorder, is a brain disorder leading to recurring seizures.
A seizure is a sudden abnormal and excessive [blank_start]firing[blank_end] of neurons. It affects 1-2% of the population. 1/3 of epilepsy is [blank_start]genetic[blank_end]. It can also be caused by: Brain injury, tumour, stroke, infections ([blank_start]meningitis, encephalitis[blank_end]), other brain disorders (Autism spectrum, dementia)
Challenges: Depression, [blank_start]mood[blank_end] disorders, ADHD, sleep, falls, [blank_start]reproductive[blank_end] issues, osteoporosis, risk of death.
Diagnosis involves [blank_start]EEG and MRI[blank_end].
Respuesta
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4th
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firing
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genetic
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meningitis, encephalitis
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mood
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reproductive
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EEG and MRI
Pregunta 2
Pregunta
Types of epilepsy:
Note - Site of discharge and extent of spread affects symptoms.
[blank_start]Simple[blank_end] (consciousness not affected) or [blank_start]Complex[blank_end] (consciousness affected)
[blank_start]Focal[blank_end] (begins and remains local) or [blank_start]Generalised[blank_end] (whole brain inc. reticular system)
Generalised can be classesd as: Absence, Myoclonic, Clonic, Tonic-clonic (very bad)
Respuesta
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Simple
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Complex
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Focal
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Generalised
Pregunta 3
Pregunta
Neural mechanisms are poorly understood.
Epileptogenesis:
• Facilitation of [blank_start]excitatory[blank_end] neurotransmission
• Reduced [blank_start]inhibitory[blank_end] transmission
• Abnormal [blank_start]electrical properties[blank_end] of cells
Repeated epileptic [blank_start]discharge[blank_end] causes cell death ([blank_start]excitotoxicity[blank_end])... this is brain damage.
Respuesta
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excitatory
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inhibitory
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electrical properties
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excitotoxicity
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discharge
Pregunta 4
Pregunta
Which of these is NOT a drug that lowers seizure threshold?
Respuesta
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Tramadol
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Lithium
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Antidepressants
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Antipsychotics
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Macrolides
Pregunta 5
Pregunta
Antiepileptic drug action is effective in 70-80% of patients.
Three main mechanisms:
• Inhibition of [blank_start]Na+ channel[blank_end] function
• Enhancement of [blank_start]GABA[blank_end] action
• Inhibition of [blank_start]Ca2+[blank_end] channel function (T type)
Pregunta 6
Pregunta
Moa: Inhibition of sodium channels.
Affect membrane excitability. Inhibit high [blank_start]frequency[blank_end] neuronal firing through their action on Na+ channels.
1. Phenytoin
[blank_start]Tonic-clonic and focal[blank_end] seizures (not absence and myoclonic). [blank_start]Non-linear[blank_end] kinetics – acute toxicity. >[blank_start]90%[blank_end] bound to plasma proteins. Hepatic metabolism CYP1A2 and 3A4. Toxicity signs: [blank_start]Nystagmus[blank_end](uncontrolled eye movements), [blank_start]diplopia[blank_end](double vision), slurred [blank_start]speech[blank_end], ataxia, confusion, hyperglycaemia. Unwanted effects: GI, drowsiness, tremor, dizziness, headache, [blank_start]gingival hypertrophy, hirsuitism, acne.[blank_end]
2. Carbamazepine
Widely used: [blank_start]focal and generalised TC[blank_end], only. Substrate and autoinducer of CYP3A4. [blank_start]Variable[blank_end] half-life (3-5 wks, OK). Decreases [blank_start]warfarin[blank_end], increases [blank_start]erythromycin[blank_end]. Adverse effects are [blank_start]dose[blank_end] related and dose limiting: headache, N&V, ataxia, drowsiness, blurred vision, [blank_start]hyponatraemia.[blank_end]
3. Sodium Valproate
All forms of epilepsy. Chemically [blank_start]unrelated[blank_end] to other antiepileptics. Increases [blank_start]GABA[blank_end] content, weak [blank_start]Na[blank_end]+ block. Interactions: AEDs([blank_start]defibrillator[blank_end]), antidepressants, antimalarials, antipsychotics, carbapenems. Unwanted Effects: GI irritation, thrombocytopenia, transient [blank_start]hair loss[blank_end], liver toxicity and pancreatitis.
4. Lamotrigine
Focal seizures, generalised tonic-clonic, [blank_start]absence, Lennox-Gastaut syndrome[blank_end]. Valproate will [blank_start]increase[blank_end] its concentration. Carbamazepine and phenytoin will [blank_start]decrease[blank_end] its concentration. SEs: Nausea, dizziness, ataxia, (serious) skin reactions
Respuesta
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frequency
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Tonic-clonic and focal
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focal and generalised TC
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absence, Lennox-Gastaut syndrome
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Non-linear
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90%
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Nystagmus
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diplopia
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speech
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gingival hypertrophy, hirsuitism, acne.
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Variable
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warfarin
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erythromycin
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dose
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hyponatraemia.
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unrelated
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GABA
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Na
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hair loss
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increase
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decrease
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anti-epileptic drugs
Pregunta 7
Pregunta
Which two sodium channel inhibitors can never be used in pregnancy?
Pregunta 8
Pregunta
MoA: Enhancement of GABA.
1. Clobazam, clonazepam - Enhances [blank_start]activation of GABA(A) R[blank_end], facilitates Cl- channel [blank_start]opening[blank_end] ([blank_start]lower[blank_end] threshold for AP)
2. Tiagabin - [blank_start]inhibits GABA uptake[blank_end].
• Confusion, difficulty [blank_start]speaking[blank_end], mild [blank_start]sedation[blank_end], paraesthesia
Overdose: lethargy, [blank_start]respiratory depression, tachycardia[blank_end]
3. Vigabatrin - [blank_start]prevents GABA breakdown[blank_end]. (GABA transaminase inhibitor.)
• 1/3 experience [blank_start]visual[blank_end] field disturbances
• [blank_start]behavioural[blank_end] adverse effects
Pregunta 9
Pregunta
MoA: Inhibition of calcium channels.
1. Ethosuximide
• Specific block of T type Calcium channels (thalamic relay)
• [blank_start]Absence[blank_end] seizures
• Side Effects: [blank_start]Nausea, anorexia, lethargy,[blank_end] dizziness, hypersensitivity (rarely)
2. Gabapentin (Pregabalin)
• T type calcium channels ([blank_start]Low[blank_end] voltage activated)
• [blank_start]Adjunct[blank_end]
Relatively SE free: [blank_start]sedation, ataxia[blank_end]. Abuse/addiction/safety risks.
3. Levetiracetam
[blank_start]Focal[blank_end] w/wo generalisation; prophylaxis post [blank_start]neurosurgery[blank_end]
• Binds to a [blank_start]synaptic vesicle glycoprotein[blank_end], SV2A
• Inhibits [blank_start]presynaptic[blank_end] calcium channels ([blank_start]N[blank_end] type)
• No CYP450 interactions
• 100% oral bioavailability
Side Effects: ataxia, dizziness, headache, tremor, behavioural disturbances, GI, [blank_start]suicidal ideation[blank_end]
Respuesta
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Absence
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Nausea, anorexia, lethargy,
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Low
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Adjunct
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sedation, ataxia
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Focal
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neurosurgery
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synaptic vesicle glycoprotein
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presynaptic
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N
-
suicidal ideation
Pregunta 10
Pregunta
Drag the drug to match the interactions and unwanted side effects. (Assessable Task...)
1. [blank_start]Phenytoin[blank_end]
UE: GI, drowsiness, tremor, dizziness, headache, gingival hypertrophy, hirsuitism, acne
Interactions: MANY including amiodarone, trimethoprim, SSRIs, TCAs, MAOIs, warfarin
2. [blank_start]Carbamazepine[blank_end]
UE: • headache, N&V, ataxia, drowsiness, blurred vision, hyponatraemia. blood, hepatic and skin disorders.
Interactions: warfarin, clopidogrel, simvastatin, oestrogens/progesterone, erythromycin
3. [blank_start]Sodium Valproate[blank_end]
UE: GI irritation, thrombocytopenia, transient hair loss, liver toxicity and pancreatitis
Interactions: [blank_start]Defibrillator[blank_end]/AEDs, antidepressants, antimalarials, antipsychotics, carbapenems
4. [blank_start]Lamotrigine[blank_end]
UE: Nausea, dizziness, ataxia, (serious) skin reactions (SJS and TEN). hypersensitivity syndrome)
Interactions: valproate, carbamazepine, phenytoin
5. [blank_start]Tiagabine[blank_end]
UE: Confusion, difficulty speaking, mild sedation, paraesthesia
6. [blank_start]Ethosuximide[blank_end]
UE: Nausea, anorexia, lethargy, dizziness, hypersensitivity (rarely)
7. [blank_start]Gabapentin (Pregabalin)[blank_end]
UE: Sedation, ataxia
8. [blank_start]Levetiracetam[blank_end]
UE: ataxia, dizziness, headache, tremor, behavioural disturbances, GI, suicidal ideation
Respuesta
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Phenytoin
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Levetiracetam
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Gabapentin (Pregabalin)
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Ethosuximide
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Tiagabine
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Lamotrigine
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Sodium Valproate
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Carbamazepine
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Anti-epileptics
Pregunta 11
Pregunta
Antiepileptic hypersensitivity syndrome: [blank_start]Rare[blank_end], potentially fatal. Between [blank_start]1-8[blank_end] wks exposure. [blank_start]Fever, rash,[blank_end] lymphadenopathy. Danger of multi-organ failure.
Risk meds: Carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone
Pregunta 12
Pregunta
Treatment is initiated after the first seizure to decrease risk and time to second seizure.
Pregunta 13
Pregunta
Common comorbidities:
• [blank_start]Psychiatric[blank_end] disorders (depression, anxiety)
• Cognitive disorders
• Migraine
• [blank_start]Sleep[blank_end] disorders
More common in people with epilepsy:
• Cardiovascular
• Respiratory
• Inflammatory disorders
Other:
- SUDEP (Sudden unexpected death in epilepsy)
- 2-6 times greater risk of [blank_start]fractures[blank_end], 35% attributed to seizures
Respuesta
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Sleep
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Psychiatric
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fractures
Pregunta 14
Pregunta
Pregnancy:
Dose adjustment needed because of [blank_start]increased[blank_end] clearance
Increased risk of teratogenicity - esp. [blank_start]first[blank_end] trimester, >[blank_start]2[blank_end] drugs. Valproate = [blank_start]neural tube[blank_end] defects, cognitive outcomes.
Breastfeeding:
Encouraged with monotherapy
Infant [blank_start]monitoring[blank_end] = sedation, feeding [blank_start]difficulties[blank_end], weight [blank_start]gain[blank_end], developmental milestones
Respuesta
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increased
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first
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2
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neural tube
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monitoring
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difficulties
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gain