Epilepsy Flashcards
Treatment for epilepsy
Epilepsy is a problem of the CORTEX
Focal Seizures
- Carbamazepine or lamotrigine
- Second line: levetiracetam, oxcarbazepine or sodium valproate
- Lamotrigine and levetiracetam is good for women of child-bearing age and also in the elderly
- Lamotrigine is favoured in the elderly with depression as a comorbidity
Generalised Tonic-Clonic Seizures
- Sodium valproate in non-childbearing aged women (due to teratogenic effects)
- Second line: lamotrigine, carbamazepine, levetiracetam
Absence Seizures* (Petit mal)
- Sodium valproate or ethosuximide
- Sodium valproate particularly effective if co-existent tonic-clonic seizures in primary generalised epilepsy
Myoclonic Seizures** (eg: juvenile myoclonic epilepsy)
- Sodium valproate
- Second line: clonazepam, lamotrigine
Genetics associated with carbamazepine
HLAB1502
- Strong association between HLAb1502 and SJS after carbamazepine
- Han chinese, thai, indian
HLAA3101 and carbamazepine
- Hypersensitivity reaction in europeans
- Maculopapular exanthema and SJS=TEN
- If a rash is developed with carbamazepine, can increase risk of developing rash in other medications, eg: phentyoin, lamotrigine,
- Lamotrigine - rash is dose dependent
What is important in testing drug levels?
- Free drug is what matters
- What affects drug concentration include
Hypoalbuminaemia states
Endogenous displacing agents such as uremia
Drugs that compete for serum protein binding sites
Note: carbamazepine autoinduces itself, will overestimate drug level it taken too early.
What is the most effective anti-epileptic dual therapy?
Lamotrigine (NMDA inhibitor, sodium channel blocker)
Valproate (potentiation of GABA activity, calcium channel blocker)
When using dual therapy,
- Combinations of AEDs with different mechanisms are more effective
- Combinations of Na+ channel blockers are not effective
What are the effects of oestrogen and progesterone for epilepsy?
- Estrogen promotes neuroexcitatory properties
- Progesterone promotes neuroinhibitory properties
Anti-epileptics to avoid during pregnancy
- Valproate: neural tube defects, facial clefts, hypospadias, lead to lower IQ in children
- Phenytoin: hypospadias, cardiac defects
Phenytoin induces vitamin K metabolism, which can cause a relative vitamin K deficiency, creating the potential for hemorrhagic disease of the newborn. The most common sites of bleeding are the umbilicus, mucous membranes, gastrointestinal tract, and venepunctures. - Carbamazepine - neural tube defects
lamotrigine, phenobarbital contribute to the risk of cardiac defects
Sodium valproate, phenytoin, phenobarbital - reduce cognitive outcomes of children
Anti-epileptics that are tolerated in pregnancy
Lamotrigine
Carbamazepine (but should avoid as teratogenic)
Keppra
Note: polytherapy is much more worse than monotherapy - try to wean patients to monotherapy prior to pregnancy
- During pregnancy, lamotrigine (increase 200-300%) and levetiracetam undergo increased clearance and require increased dosing
- Carbamazepine remains stable
RF for Sudden Unexpected Death in Epilepsy
GTCS > 2 years
Nocturnal seizures
Treatment resistant seizures
Long duration of epilepsy and early age of onset
Dravet syndrome - sodium channel gene mutation
Tends to occur at night (80% unwitnessed)
What neuro transmitters are involved in epilepsy?
- Excitatory neurotransmitter: glutamate
- Inhibitory neurotransmitter: GABA
Anticonvulsants act to either reduce excitatory signals or amplify inhibitory signals.
Carbamazepine
- Indication
- MOA
- Side effects
Indication:
- First line for focal and generalised tonic/clonic seizures
- Trigeminal neuralgia
MOA: Sodium channel blocker
SE:
- Strong association between HLAb1502 and SJS after carbamazepine
- Diplopia
- Aplastic anaemia/agranulocytosis
- Hyponatremia
- Hepatotoxicity
what are the strong inducers of cytochrome p450?
Rifampicin and carbamazepine are some of the strongest inducers of cytochrome P450 enzymes and can thus interact with many drugs.
Which drugs are eliminated by zero order kinetics?
Zero order kinetics: elimination rate (green line) is independent of plasma drug concentration and, therefore, remains constant, resulting in a decreasing t½ (half-life) with decreasing drug concentration.
It takes zero PHEN-tAS-E (fantasy) to remember the drugs that are eliminated by zero-order kinetics: PHENytoin, ASpirin, Ethanol, Theophylline
Levetiracetam/Brivaracetam
- MOA
- Side effects
MOA:
- Inhibits presynaptic calcium channels reducing neurotransmitter release an and act as a neuromodulator
Modulation of SV2A mediated neurotransmitter release
SE:
- Sedation
- Dizziness
- Psychiatric symptoms: psychosis, depression
Which anti-epileptic agents are broad spectrum vs narrow spectrum
Broad Spectrum: lamotrigine, levetiracetam, topiramate, valproate - can treat generalised and focal seizures
Narrow Spectrum: carbamazepine, gabapentin, phenytoin
Phenytoin
MOA
SE
MOA:
Sodium channel blocker
SE (PHENYTOIN)
- cytochrome p450 interaction
- hirsutism
- enlarged gums (gingival hyperplasia)
- Nystagmus, ataxia, diplopia (dose related)
- Yellow browning of skin
- Teratogenic
- Osteomalacia
- Interacts with folate - megaloblastic anaemia (secondary to altered folate metabolism)
- Neuropathy
Intravenous phenytoin can cause hypotension and bradyarrhythmias. Phenytoin is believed to protect against seizures by causing voltage-dependent block of voltage gated sodium channels. Phenytoin is also a class IB antiarrhythmic drugs which blocks sodium channels in the heart resulting in shortening of repolarization.
