Anti-epileptics Flashcards
What is epilepsy?
Episodic discharge of abnormal high frequency electrical activity in the brain, leading to seizure.
(Must be RECURRENT for diagnosis)
What is the prevalence of epilepsy?
0.5-1.0%
What proportion of patients are therapeutics effective for?
Around 75%
What causes epilepsy?
Increased excitatory activity
Decreased inhibitory activity
Loss of homeostatic control
Spread of neuronal activity
What are the two main types of seizure?
Partial seizures
Generalised seizures
What are partial seizures?
Loss of local excitatory/inhibitory homeostasis
Increased discharge in focal cortical areas
(May be simple (conscious) or complex (impaired consciousness))
What are partial seizures?
Loss of local excitatory/inhibitory homeostasis
Increased discharge in focal cortical areas
(May be simple (conscious) or complex (impaired consciousness))
What are the symptoms of partial seizures?
They reflect the area affected
(eg: involuntary motor disturbance, behavioural change, aura)
May become secondary generalised
What are generalised seizures?
Generated centrally and spread through both hemispheres, with total loss of consciousness.
Eg: tonic-clonic (60%, grand mal), absence (5%, petit mal), other types.
How long are most seizures?
Up to 5 minutes
May be prolonged beyond this or be a series of seizures without recovery (status epilepticus) - can be any kind, medical emergency
What are the therapeutic targets for treatment?
Voltage gated sodium channel blockers
Enhancing GABA mediated inhibition
How to VGSC blockers work?
Bind to alpha subunit of the channel and prevent movement of the inactivation gate, keeping the gate in its closed conformation. (Only binds when depolarised)
Reduces likelihood of high spiking activity by prolonging inactivation state and reducing the firing rate.
Dissociates once membrane potential returns to normal.
What is carbamzepine?
A VGSC blocker.
Well absorbed, 75% protein bound.
Linear PK, initial half life 30 hours (repeated use > 15 hours, as it induces CYP450)
What are the ADRs of carbamezepine?
CNS - dizziness, drowsiness, ataxia, numbness, tingling, motor disturbance
GI - upset vomiting
CVS - BP variation
Rashes, hyponatremia
What are the DDIs for carbamezepine?
CYP450 inducer therefore warfarin, systemic corticosteroids, oral contraceptives decreased.
Displaced by albumin bound higher affinity drugs.
SSRIs MAOIs TCAs, and TCA interfere with action.
What is carbamezepine used to treat?
Generalised tonic-clonic seizures
All partial seizures
NOT absence seizures
What is phenytoin?
A VGSC blocker
Well absorbed, 90% albumin bound
CYP450 inducer but does not affect its own metabolism.
Nonlinear PK at therapeutic concs - T1/2 6-24 hours, variable
What are the ADRs of phenytoin?
CNS - dizziness, ataxia, headache, nystagmus, nervousness
Gingival hyperplasia
Rashes - hypersensitivity, Stevens Johnson
What are the DDIs of phenytoin?
Competitive binding (eg: valproate, NSAIDs, salicylate) exacerbates nonlinear PK and ^ plasma levels
Reduces effect of oral contraceptives
Cimetidine improves phenytoin’s effect
