Anti-epileptics

Question 1

What is epilepsy?

Answer 1

Episodic discharge of abnormal high frequency electrical activity in the brain, leading to seizure.
(Must be RECURRENT for diagnosis)

Question 2

What is the prevalence of epilepsy?

Answer 2

0.5-1.0%

Question 3

What proportion of patients are therapeutics effective for?

Answer 3

Around 75%

Question 4

What causes epilepsy?

Answer 4

Increased excitatory activity
Decreased inhibitory activity
Loss of homeostatic control
Spread of neuronal activity

Question 5

What are the two main types of seizure?

Answer 5

Partial seizures

Generalised seizures

Question 6

What are partial seizures?

Answer 6

Loss of local excitatory/inhibitory homeostasis
Increased discharge in focal cortical areas
(May be simple (conscious) or complex (impaired consciousness))

Question 7

What are partial seizures?

Answer 7

Loss of local excitatory/inhibitory homeostasis
Increased discharge in focal cortical areas
(May be simple (conscious) or complex (impaired consciousness))

Question 8

What are the symptoms of partial seizures?

Answer 8

They reflect the area affected
(eg: involuntary motor disturbance, behavioural change, aura)
May become secondary generalised

Question 9

What are generalised seizures?

Answer 9

Generated centrally and spread through both hemispheres, with total loss of consciousness.
Eg: tonic-clonic (60%, grand mal), absence (5%, petit mal), other types.

Question 10

How long are most seizures?

Answer 10

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

Question 11

What are the therapeutic targets for treatment?

Answer 11

Voltage gated sodium channel blockers

Enhancing GABA mediated inhibition

Question 12

How to VGSC blockers work?

Answer 12

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.

Question 13

What is carbamzepine?

Answer 13

A VGSC blocker.
Well absorbed, 75% protein bound.
Linear PK, initial half life 30 hours (repeated use > 15 hours, as it induces CYP450)

Question 14

What are the ADRs of carbamezepine?

Answer 14

CNS - dizziness, drowsiness, ataxia, numbness, tingling, motor disturbance
GI - upset vomiting
CVS - BP variation
Rashes, hyponatremia

Question 15

What are the DDIs for carbamezepine?

Answer 15

CYP450 inducer therefore warfarin, systemic corticosteroids, oral contraceptives decreased.
Displaced by albumin bound higher affinity drugs.
SSRIs MAOIs TCAs, and TCA interfere with action.

Question 16

What is carbamezepine used to treat?

Answer 16

Generalised tonic-clonic seizures
All partial seizures
NOT absence seizures

Question 17

What is phenytoin?

Answer 17

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

Question 18

What are the ADRs of phenytoin?

Answer 18

CNS - dizziness, ataxia, headache, nystagmus, nervousness
Gingival hyperplasia
Rashes - hypersensitivity, Stevens Johnson

Question 19

What are the DDIs of phenytoin?

Answer 19

Competitive binding (eg: valproate, NSAIDs, salicylate) exacerbates nonlinear PK and ^ plasma levels
Reduces effect of oral contraceptives
Cimetidine improves phenytoin’s effect