NE3 Epilepsy

Epilepsy, the ❌ most common neurological disorder, is a brain disorder leading to recurring seizures.
A seizure is a sudden abnormal and excessive ❌ of neurons. It affects 1-2% of the population. 1/3 of epilepsy is ❌. It can also be caused by: Brain injury, tumour, stroke, infections (❌), other brain disorders (Autism spectrum, dementia)
Challenges: Depression, ❌ disorders, ADHD, sleep, falls, ❌ issues, osteoporosis, risk of death.
Diagnosis involves ❌.

Types of epilepsy:
Note - Site of discharge and extent of spread affects symptoms.

❌ (consciousness not affected) or ❌ (consciousness affected)
❌ (begins and remains local) or ❌ (whole brain inc. reticular system)
Generalised can be classesd as: Absence, Myoclonic, Clonic, Tonic-clonic (very bad)

Neural mechanisms are poorly understood.
Epileptogenesis:
• Facilitation of ❌ neurotransmission
• Reduced ❌ transmission
• Abnormal ❌ of cells
Repeated epileptic ❌ causes cell death (❌)... this is brain damage.

Antiepileptic drug action is effective in 70-80% of patients.
Three main mechanisms:
• Inhibition of ❌ function
• Enhancement of ❌ action
• Inhibition of ❌ channel function (T type)

Moa: Inhibition of sodium channels.
Affect membrane excitability. Inhibit high ❌ neuronal firing through their action on Na+ channels.

1. Phenytoin
❌ seizures (not absence and myoclonic). ❌ kinetics – acute toxicity. >❌ bound to plasma proteins. Hepatic metabolism CYP1A2 and 3A4. Toxicity signs: ❌(uncontrolled eye movements), ❌(double vision), slurred ❌, ataxia, confusion, hyperglycaemia. Unwanted effects: GI, drowsiness, tremor, dizziness, headache, ❌

2. Carbamazepine
Widely used: ❌, only. Substrate and autoinducer of CYP3A4. ❌ half-life (3-5 wks, OK). Decreases ❌, increases ❌. Adverse effects are ❌ related and dose limiting: headache, N&V, ataxia, drowsiness, blurred vision, ❌

3. Sodium Valproate
All forms of epilepsy. Chemically ❌ to other antiepileptics. Increases ❌ content, weak ❌+ block. Interactions: AEDs(❌), antidepressants, antimalarials, antipsychotics, carbapenems. Unwanted Effects: GI irritation, thrombocytopenia, transient ❌, liver toxicity and pancreatitis.

4. Lamotrigine
Focal seizures, generalised tonic-clonic, ❌. Valproate will ❌ its concentration. Carbamazepine and phenytoin will ❌ its concentration. SEs: Nausea, dizziness, ataxia, (serious) skin reactions

MoA: Enhancement of GABA.

1. Clobazam, clonazepam - Enhances ❌, facilitates Cl- channel ❌ (❌ threshold for AP)

2. Tiagabin - ❌.
• Confusion, difficulty ❌, mild ❌, paraesthesia
Overdose: lethargy, ❌

3. Vigabatrin - ❌. (GABA transaminase inhibitor.)
• 1/3 experience ❌ field disturbances
• ❌ adverse effects

MoA: Inhibition of calcium channels.

1. Ethosuximide
• Specific block of T type Calcium channels (thalamic relay)
• ❌ seizures
• Side Effects: ❌ dizziness, hypersensitivity (rarely)

2. Gabapentin (Pregabalin)
• T type calcium channels (❌ voltage activated)
• ❌
Relatively SE free: ❌. Abuse/addiction/safety risks.

3. Levetiracetam
❌ w/wo generalisation; prophylaxis post ❌
• Binds to a ❌, SV2A
• Inhibits ❌ calcium channels (❌ type)
• No CYP450 interactions
• 100% oral bioavailability
Side Effects: ataxia, dizziness, headache, tremor, behavioural disturbances, GI, ❌

Drag the drug to match the interactions and unwanted side effects. (Assessable Task...)

1. ❌
UE: GI, drowsiness, tremor, dizziness, headache, gingival hypertrophy, hirsuitism, acne
Interactions: MANY including amiodarone, trimethoprim, SSRIs, TCAs, MAOIs, warfarin

2. ❌
UE: • headache, N&V, ataxia, drowsiness, blurred vision, hyponatraemia. blood, hepatic and skin disorders.
Interactions: warfarin, clopidogrel, simvastatin, oestrogens/progesterone, erythromycin

3. ❌
UE: GI irritation, thrombocytopenia, transient hair loss, liver toxicity and pancreatitis
Interactions: ❌/AEDs, antidepressants, antimalarials, antipsychotics, carbapenems

4. ❌
UE: Nausea, dizziness, ataxia, (serious) skin reactions (SJS and TEN). hypersensitivity syndrome)
Interactions: valproate, carbamazepine, phenytoin

5. ❌
UE: Confusion, difficulty speaking, mild sedation, paraesthesia

6. ❌
UE: Nausea, anorexia, lethargy, dizziness, hypersensitivity (rarely)

7. ❌
UE: Sedation, ataxia

8. ❌
UE: ataxia, dizziness, headache, tremor, behavioural disturbances, GI, suicidal ideation

Antiepileptic hypersensitivity syndrome: ❌, potentially fatal. Between ❌ wks exposure. ❌ lymphadenopathy. Danger of multi-organ failure.
Risk meds: Carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone

Common comorbidities:
• ❌ disorders (depression, anxiety)
• Cognitive disorders
• Migraine
• ❌ disorders
More common in people with epilepsy:
• Cardiovascular
• Respiratory
• Inflammatory disorders
Other:
- SUDEP (Sudden unexpected death in epilepsy)
- 2-6 times greater risk of ❌, 35% attributed to seizures

Pregnancy:
Dose adjustment needed because of ❌ clearance
Increased risk of teratogenicity - esp. ❌ trimester, >❌ drugs. Valproate = ❌ defects, cognitive outcomes.
Breastfeeding:
Encouraged with monotherapy
Infant ❌ = sedation, feeding ❌, weight ❌, developmental milestones