Epilepsy (2) Flashcards
1
Q
So- How do we treat epilepsy
A
- Restore balance between excitation and inhibition
- Anti-convulsant (Stop a seizure)
- Prevent damage to network and maladaptive response
- Antiepileptics (Stop epilepsy)
2
Q
Epilepsy treatment in history
A
3
Q
Most AEDs have a synaptic action
A
- Directly switch on post-synaptic GABA receptors (topiramate, gabapentin)
- Inhibit activity of Glu
4
Q
Drugs acting at glutamatergic synapse
Drugs that reduce glutamatergic release
A
- Na-channel block- prevent AP therefore no influx of sodium which means that voltage gated calcium channels will not be activated- no efflux of glutamate
- Lamotrigine ++
- Carbamazepine ++
- Phenytoin ++
- Sodium Valproate +
- Ca- channel block- prevent release of glutamate via calcium dependent exocytosis
- Gabapentin
- Pregabalin
5
Q
Drugs acting at GABA synapses
A
- Presynaptic
- vigabatrin ++
- Sodium Valporate +
- GABA transaminase inhibitor blocks GABA breakdown increases GABA levels increases GABA release- CBD
- GABAA transporter- tiagabine
- Block GABA reuptake (pre-synaptically) increases GABA in cleft-
- Post-Synapse GABAA receptor
- Increase post-synapstic response prolong channel open time
6
Q
Diagnosis of epilepsy
A
- After a second seizure
- Diagnosis by a specialist (neurology) is required
- EEG is used to confirm (But may not help)
- May need to be repeated
- May need to be long-term (ambulatory)
- EEG may need to be during sleep (most seizures)
- May require sleep deprivation of melatonin administration
- Seizures may be provoked (Light)
- Neuroimaging (MRI, MEG) required if diagnosis of idiopathic generalized epilepsy is made (WHY)
7
Q
Treatment with anti-epileptic drugs (AED)
A
- Treatment starts after the 2nd seizure (But after first if there is clear evidence of EEG abnormality, structural abnormality or neurological deficit
- Monotherapy is the goal (why?)-
- Side effect profile
- Drug interactions- AED can be either inducers or inhibitors of CYP enzymes
- When switching from one AED to another, careful tapering (both drugs) is needed
- Control risk of having a seizure- 2nd one may not work
- Adjunct therapy considered when Pt does not achieve seizure freedom
- Status epilepticus is an acute emergency
- 1 or more seziures over an extended period of time
8
Q
Choosing anti-epileptic drugs
A
- Seizure type
- Epilepsy syndrome (west syndrome- multiple different types of seizures in 1 syndrome)
- PK profile patient
- Interactions/Other medical conditions
- Efficacy
- Expected ADR
- Cost
9
Q
Choosing anti-epileptic drugs
Focal seizures
A
- Carbamazepine (CBZ) or Lamotrigine (LTG) 1st line for children, young people and adults
- Levetiracetam, oxcarbazepine or sodium valporate if CBZ or LTG ineffective or not tolerated
- If these 5 drugs do not work then consider: Eslicarbazepine acetate, Lacosamide, Phenobarbital, Phenytoin, Pregabalin, Tiagabine, Vigabatrin, Zonisamide
- Issue 1: The risk-benefit ratio when using vigabatrin because of the risk of an irreversible effect on visual fields (severe, symptomatic, persistent field constriction
- Issue 2: Valporate- Teratogenic (birth deformity)- treatment must not be used in girls/women including girls below the age of puberty, unless alternative treatments are not suitable and unless the conditions of the pregnancy prevention programme are met
- Valporate must not be used in pregnant women
10
Q
Choosing anti-epileptic drugs
Generalised tonic-clonic seizures (GCTS)
A
- Over the whole of the cortex
- Valporate is offered first to children and young people newly diagnosed with GCTS
- Valproate is a fatty acid and similar to cannabis oil
- LTG is offered second (may exacerbate myoclonic seizures)
- CBZ and oxcarbazepine may be offered but risk augmenting absence and myoclonic seizures
11
Q
Choosing anti-epileptic drugs
Absence seizures
A
- Transient loss of consciousness
- Valporate or ethosuximide is offered first to children and young people
- LTG is offered second
- If these 2 drugs do not work adjunct with 2 of these three drugs: ETX, VAL, LTG
- If adjunct therapy ineffective try clobazam, levetiracetam, topiramate, zonisamide
- Don’t use: CBZ, gabapentin, phenytoin, pregabalin, tiagabine, vigabatrin, oxcarbazepine
- These are because these induce absence seizures
12
Q
Choosing anti-epileptic drugs
Myoclonic seizures-Limb that jerks
A
- Valporate is offered first to children and young people
- Levetiracetam or topiramate offered second
- If adjunct therapy ineffective try clobazam, levetiracetam, topiramate, zonisamide
- Don’t use: CBZ, gabapentin, phenytoin, pregabalin, tiagabine, vigabatrin, oxcarbazepine
- Induce and make seizures worse
13
Q
Choosing anti-epileptic drugs
Dravet syndrome and Lennox-Gastaut syndrome
A
- Devastating seizure syndromes with 10-100 seizures per day, treatment-resistant, associated with sodium channel mutations (Dravet)
- Or in case of LGS, anoxia abnormal development of the brain cortex (cortical dysplasia), congenital infections, stroke trauma, reduced oxygen supply that occurs before birth (perinatal hypoxia), infections of the central nervous system such as encephalitis or meningitis and are a rare, genetic disorder called tuberous sclerosis
- Very difficult to treat requires specialist
- CBD, fenfluramine (blocks 5-HT- cause heart valve damage) have proved effective also valporate
- Felbamate (NMDAR blocker- however people may get fatal aplastic anemia or liver damage) may be used as a drug of last resort in specialist centres
14
Q
Choosing anti-epileptic drugs
Cannabidiol (CBD)
A
- 38-41% reduction in seizures even in Dravet/LGS
- Similar effectiveness to previous AED
- May be effective in preventing refractory status epilepticus
15
Q
ADR of AED
A
- Acute dose-related- reversible
- Idiosyncratic- drug and person specific
- Uncommon
- Potentially serious or life-threatening
- Chronic- reversibility and seriousness vary
29
Q
Summary
A
