Epilepsy Flashcards
Explain Carbamazepine as a treatment option for epilepsy.
- Indication: focal, and potentially for 1° or 2° generalised tonic clinic
- Mechanism: act by producing use-dependent blockade of voltage-gated sodium channels and stabilising excitatory neuronal cell membranes. This suppresses repetitive neuronal discharges and reduces synaptic propagation of excitatory impulses associated with seizures and pain transmission.
- Side effects: headache, ataxia, blurred vision, nausea, drowsiness, dizziness, allergic-skin reactions, DRESS
- Interactions: reduces efficacy of oral contraceptives, CYP3A4 inducer
Monitoring: FBC every 3-6 months for leucopenia and aplastic anaemia.
Explain DRESS and what drugs cause it
DRESS is a hypersensitivity reaction to a drug, characterised by fever, skin rash, and haematological abnormalities.
AED drugs causing DRESS include phenytoin, phenobarbital, and carbamazepine.
Explain Sodium Valproate as a treatment option for epilepsy.
- Indications: efficacious for all forms of seizures, including focal and GTCS
- Mechanism: produces use-dependent blockade of voltage-dependent sodium channels and enhances brain concentrations of GABA, an inhibitory neurotransmitter. This suppresses repetitive neuronal discharge that generates seizures in epilepsy.
- Side effects: nausea, vomiting, hair loss, tremor, easy bruising, weight gain
o Rarely encephalopathy, acute pancreatitis - Contraindication: hepatotoxicity, pregnancy and childbearing age
o Associated with major malformations and neurodevelopmental problems in neonates
Explain Lamotrigine as a treatment option for epilepsy.
- Indications: adjunct for focal or GTCS, or monotherapy (unapproved)
- Role in therapy: well-tolerated in patients but requires up-titration time (i.e. avoid if immediate seizure relief required)
- Mechanism: produces use-dependent blockade of voltage-gated sodium channels and by inhibiting glutamate release. This stabilises excitatory neuronal cell membranes and suppresses repetitive neuronal discharges that generate seizures in epilepsy.
- Side effects: nausea, dizziness, ataxia, blurred vision, behavioural changes, serious skin reactions (often with fever)
- Interactions: reduces the efficacy of oral contraceptives
Explain Levetiracetam as a treatment option for epilepsy.
- Indication: monotherapy focal seizure, or adjunct in GTCS (monotherapy used in practice by not approved), effect is rapid and can reach maximum dose quicker than other AED
- Role: medium efficacy but can be initiated quickly to maximum dose
- Mechanism: inhibits seizure activity by blocking N-type voltage-gated calcium channels and/or by binding synaptic vesicular protein SV2A and modulating neurotransmitter release.
- Side effects: ataxia, dizziness, headache, tremor, behavioural disturbances, GI suicidal ideation, neuropsychiatric effects
- Monitor: depression or suicidal behaviour
Explain Phenytoin as a treatment option for epilepsy.
- Indications: all seizures, including focal and GTCS
- Role: status epilepticus, not generally used in seizures due to ADR’s and TDM
- Mechanism: produces use-dependent blockade of voltage-gated sodium channels and by inhibiting glutamate release. This stabilises excitatory neuronal cell membranes and suppresses repetitive neuronal discharges that generate seizures in epilepsy.
- Side effects: Gi disturbances, drowsiness, tremor, dizziness, headache, gingival hypertrophy, hirsutism, acne
o In toxicity: nystagmus, diplopia, slurred speech, ataxia, confusion, hyperglycaemia - Caution: dose variability, especially in pregnant women or elderly patients
Explain Topiramate as a treatment option for epilepsy.
- Indication: focal and generalised onset seizures
- Mechanism: block sodium channels, and potentiates GABA activity and inhibit glutamate
- Side effects: renal stone formation, decreased sweating, weight loss, depression, dizziness, eye problems, glaucoma
- Interactions: pregnancy risk (1% more than general population
Explain the patient counselling points for a patient with seizures concerned about driving
Driving
- Eligibility criteria for epileptic patients:
If the patient has been seizure-free for at least a year, or
o If the patient, who only has epileptic attacks when asleep, has established 3 years of asleep attacks without awake attacks.
Patients are not recommended to drive during medication changes or withdrawal of epileptic drugs.
Patients with a first or single epileptic seizure must not drive for 12 months (or 5 years for goods or passenger-carrying vehicles).
Explain the patient counselling points for a patient taking levetiracetam or lamotrigine
Risk of Suicidal Thoughts & Behaviour
Antiepileptic medicines have been associated with a small increased risk of suicidal thoughts and behaviour, regardless of the indication.
Symptoms can occur at any point in treatment.
Monitor closely for changes in behaviour that can indicate suicidality.
Explain the treatment goals of epilepsy
Control seizures rapidly, using the lowest effective dose of, ideally, a single agent, without intolerable ADRs
Monotherapy – fewer side effects and interactions, less expensive, improves adherence
Continue AED monotherapy until patient remains seizure free for at least 2 years
Also:
* Reduce risk of death, injury, status
* Facilitate return to driving, work
* Reduce risk of cognitive dysfunction
* Patient/family anxiety
* Improve prognosis
Explain the pathophysiology of Epilepsy
Epilepsy is a neurological disorder characterised by recurrent (two or more) seizures.
Epileptic seizures are characterised by episodic high-frequency neuronal discharge due to an excitatory and inhibitory neurotransmitter release imbalance.
Excess excitatory neurotransmitters or a deficit in inhibitory neurotransmitters leads to postsynaptic neuronal activation and over-firing of the action potential.
Explain the formulation considerations for AED
Phenytoin: non-linear PK and requires TDM, 90% plasma protein bound that requires dose adjustment in elderly or pregnant, long-half life, especially in renally impaired, different formulations not bioequivalent. Interacts with CYP3A4 and CYP1A2
Carbamazepine: MR available reduces ADRs and alters timing of dose, 70% protein bound, metabolised and induces CYP3A4 (caution for statins and oestrogen)
Levetiracetam: available as oral or IV, no interactions, adjust in renal impairment, can be up titrated to maximum dose quickly
Lamotrigine: interacts with oestrogen, available as a chewable or dispersible tablet
Sodium valproate: severely teratogenic, available as a tablet, liquid or injection,
Explain the law and ethics that pertain to an epileptic patient
NZ Transport Agency states that no individual is to drive 12 months after a seizure, unless at the agency’s discretion.
LTA 18 states that health practitioners consider the mental and physical health of the patient is such that, for public safety, should only drive motor vehicles warranted by their health.
LTA 12 states that no person should drive a motor vehicle under the influence of alcohol or drugs, or both that would warrant them incapable of having proper control of the vehicle.
HDC Code of Rights: right to service of an appropriate standard(4), right to effective communication, right to fully informed (6), right to informed consent (7)
