Anti-Epileptic Drugs

Question 1

Outline the basic prescribe rules of AEDs

Answer 1

Always consult neurology when planning to alter

Aim for monotherapy

Aim to start at low dose and increase slowly

Question 2

Outline how seizures are classified

Answer 2

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)

Question 3

What are the symptoms of a partial seizure?

Answer 3

Involuntary motor disturbance

Behavioural change

Impending focal spread accompanied by ‘Aura’ eg unusual smell or taste, déjà vu / jamais vu

Question 4

What is status epilepticus?

Answer 4

Prolonged seizure

If not treated = interrupted breathing = hypoxia = brain damage

Priorities = ABC

Treat = benzodiazepines (lorazepam), phenytoin (requires cardiac monitoring)

Question 5

What are the primary causes of epilepsy?

Answer 5

No identifiable cause = idiopathic

Question 6

What are the secondary causes of epilepsy?

Answer 6

Medical conditions affecting the brain

Vascular disease, tumour = deficit in balance between excitation and inhibition = precipitation of seizure

Question 7

What are the major precipitants of epilepsy?

Answer 7

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

Question 8

How is epilepsy generated in the brain?

Answer 8

Increased excitatory activity

Decreased inhibitory activity

Loss of homeostatic control

Spread of neuronal hyperactivity

Question 9

Why is untreated epilepsy a life threatening condition?

Answer 9

Physical injury – fall/crash

Hypoxia

SUDEP – sudden death in epilepsy

Brain dysfunction/damage

Cognitive impairment

Question 10

How does a VGSC blocker work?

Answer 10

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

Question 11

Discuss carbamezepine

Answer 11

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

Question 12

Discuss phenytoin

Answer 12

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

Question 13

Discuss lamotrigine

Answer 13

PARTIAL + GENERAL

Prolonges VGSC inactive state

No CYP450 induction

ADRs = mild/serious skin rashes

DDIs = oral contraceptive increase the clearance of lamotrigine

Least teratogenic

Question 14

What are the therapeutic targets for AEDs?

Answer 14

Voltage gated Na channel blocker

GABA increase

Question 15

How does valproate increase GABA?

Answer 15

Weak Inhibition of GABA inactivation enzymes – GABA increased

Weak Stimulus of GABA synthesising enzymes - GABA increased

Question 16

Discuss sodium valproate

Answer 16

GENERALISED

Increases GABA

ADRs = teratogenic, weight gain

DDIs = antidepressants inhib action, aspirin competitive binding in plasma

Question 17

Discuss benzodiazepines

Answer 17

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

Question 18

Why is anti-convulsant therapy a concern in pregnancy?

Answer 18

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)

Question 19

Outline the mechanism of increased GABA

Answer 19

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