Anti-Epileptic Drugs Flashcards
Outline the basic prescribe rules of AEDs
Always consult neurology when planning to alter
Aim for monotherapy
Aim to start at low dose and increase slowly
Outline how seizures are classified
Partial = simple (conscious), complex (impaired consciousness)
Generalised = lose consciousness, involve the entirety of the cortex
- tonic-clonic (60%) (convulsions)
- absence (5%)
- atonic (drop)
- myoclonic (jerks)
What are the symptoms of a partial seizure?
Involuntary motor disturbance
Behavioural change
Impending focal spread accompanied by ‘Aura’ eg unusual smell or taste, déjà vu / jamais vu
What is status epilepticus?
Prolonged seizure
If not treated = interrupted breathing = hypoxia = brain damage
Priorities = ABC
Treat = benzodiazepines (lorazepam), phenytoin (requires cardiac monitoring)
What are the primary causes of epilepsy?
No identifiable cause = idiopathic
What are the secondary causes of epilepsy?
Medical conditions affecting the brain
Vascular disease, tumour = deficit in balance between excitation and inhibition = precipitation of seizure
What are the major precipitants of epilepsy?
Sensory stimuli = flashing lights
Brain disease/trauma = injury, stroke, haemorrhage, drugs, lesion
Metabolic disturbance = hypoglycaemia/calcaemia/natraemia
Infections = febrile convulsions in infants
Therapeutics = some drugs lower fit threshold
How is epilepsy generated in the brain?
Increased excitatory activity
Decreased inhibitory activity
Loss of homeostatic control
Spread of neuronal hyperactivity
Why is untreated epilepsy a life threatening condition?
Physical injury – fall/crash
Hypoxia
SUDEP – sudden death in epilepsy
Brain dysfunction/damage
Cognitive impairment
How does a VGSC blocker work?
Bind the inside of the channel during membrane depolarisation (inactive) = locking it in an inactive state
Stops subsequent firing = neurone goes back to a more normal level of excitability
Discuss carbamezepine
PARTIAL
VGSC blocker
Strong inducer of CYP450 = repeated use reduces its own half-life
ADRs = dizziness, drowsy, ataxia, motor disturbance, numbness, tingling
DDIs = decreased effect of warfarin, OCP, steroids, phenytoin
Discuss phenytoin
STATUS EPILEPTICUS + ACUTE
Can also be used for generalised Tonic-Clonic and all partial
Prolonges VGSC inactivation state
CYP450 inducer
ADRs = gingival hyperplasia, rashes
DDIs = decreased effect of warfarin, OCP, steroids
Discuss lamotrigine
PARTIAL + GENERAL
Prolonges VGSC inactive state
No CYP450 induction
ADRs = mild/serious skin rashes
DDIs = oral contraceptive increase the clearance of lamotrigine
Least teratogenic
What are the therapeutic targets for AEDs?
Voltage gated Na channel blocker
GABA increase
How does valproate increase GABA?
Weak Inhibition of GABA inactivation enzymes – GABA increased
Weak Stimulus of GABA synthesising enzymes - GABA increased
Discuss sodium valproate
GENERALISED
Increases GABA
ADRs = teratogenic, weight gain
DDIs = antidepressants inhib action, aspirin competitive binding in plasma
Discuss benzodiazepines
STATUS EPILEPTICUS + ACUTE
E.g. Lorazepam, diazepam
Act on GABA Cl channel = increases Cl into neurone = increased threshold for AP generation
ADRs = sedation, tolerance with chronic use, confusion, aggression, resp/CNS depression
Why is anti-convulsant therapy a concern in pregnancy?
Teratogenicity – congenital malformation
Harm to both mother and baby if treatment is stopped
Failure of contraception = 4-8%
Valproate = neural tube defects (BEST AVOIDED) – use folate supplements
Following birth – learning diff, mild neurological dysfunction
Lamotrigine (MAY BE SAFEST)
Outline the mechanism of increased GABA
Increased GABA = increased inhibition
GABA bind Cl channels = hyperpolarise cell (more -ve) = natural anticonvulsant
Enhanced GABA mediated inhibition =
1) inhibition of GABA inactivation
2) inhibition of GABA re-uptake
3) increased rate of GABA synthesis
