11 Anticonvulsants

Question 1

Definition of seizure, epilepsy, and convulsions

Answer 1

Seizure: abnormal movements or behaviours due to unusual electrical activity in the brain

Epilepsy: a group of related disorders causing recurrent seizures

Convulsion: repeated rapid body muscles contraction and relaxation resulting in an uncontrolled shaking of the body.

Question 2

Causes and types of seizures

Answer 2

Causes:
Primary: idiopathic

Secondary: brain damage, infection, inherited factors, drug-induced condition

Types:

Partial:

1) Simple ( no alteration of consciousness)
2) Complex (alteration of consciousness)

Generalised:

1) Tonic- clonic ( strong contraction of the whole body and uncontrolled jerking)
2) Absence ( sudden unresponsiveness for a short duration with little or no disturbance)
3) Myoclonic (brief muscle spasm)
4) Atonic ( brief lapse in muscle tone)

Status Epilepticus
Epileptic seizure > 5 min
or >1 seizure within 5 min without returning to normal in between

Question 3

Biological basis and pharmacology of anticonvulsant drugs

Answer 3

Biological basis:
Drug therapy:
↑GABA action
↓glutamate action

Absence seizure: T type Ca2+ channel inhibition

Pharmacology:

1. Inhibiting voltage-gated sodium channels
2. enhancing the function of GABAA receptors
3. inhibiting GABA transaminase
4. multiple actions

Question 4

Phenytoin, carbamazepine

Answer 4

Mechanism:

• inhibit voltage gated Na+ channel
• use dependent inhibition
• reduce neuron excitability
• long half life
• cytochrome p450 inducer
• useful for generalised and partial seizures but not absence seizures

Phenytoin:
- high plasma binding
- undesirable effects: confusion, gum hyperplasia, skin rashes,
anaemia, teratogenicity

Carbamazepine:
- undesirable effects ( low incidence): sedation, blurred vision,
ataxia, water retention, GI/CV effects, Steven Johnson syndrome
- most widely used antiepileptic

Question 5

Phenobarbitol

Answer 5

Mechanism:
-enhance GABAA receptor activity
- facilitate opening of GABA-activated
Cl- channel
-hyperpolarization -->  inhibition
-useful for generalised and partial seizures but not absence seizures
-cytochrome P450 inducer 

Undesirable effects:
sedation, hepatitis, impairments in cognitive and motor performance, hypotension, respiratory depression

• fatal in overdose
• must not be given to patients with porphyria

Question 6

Ethosuximide

Answer 6

Mechanism:

• Inhibit T-type Ca2+ channels
• For absences seizure only
• may exacerbate tonic–clonic seizures

Undesirable effects: nausea, anorexia, epigastric pain, drowsiness

Question 7

Clonazepam

Answer 7

Mechanism:
-increase GABAA receptor affinity to
GABA   
-enhance inhibitory action of GABA  
-anticonvulsant effect mediated by α1- subunit
-inhibit T type Ca2+ channels
- treat all types of seizures

Undesirable effects:

• sedation
• withdrawal syndrome

Question 8

Vigabatrin

Answer 8

Mechanism:
-irreversibly inhibit GABA-
transaminase (for inactivating GABA to succinic semialdehyde)
- treat all types of seizures

Undesirable side effects: causing visual field defects
(limiting the clinical use of vigabatrin), sedation, mood change

Question 9

Valproate

Answer 9

Mechanism:

• inhibit Na+ channels
• inhibit GABA-transaminase
• inhibit T-type Ca2+ channels
• treat all types of seizures
• non sedative
• cytochrome p450 inhibitor
• highly protein bound

Undesirable effects: hepatotoxicity (rare), teratogenicity
(fetal malformation)

Question 10

Gabapentin, pregabablin

Answer 10

Mechanism:

• GABA-mimetic
• Exact mechanism unclear
• treat partial seizures

Undesirable effects:
mainly sedation

Question 11

Lamotrigine

Answer 11

Mechanism:

• act on T-type Ca2+ channels and Na+ channels
• Inhibit the release of glutamate
• Treat all types of seizures

Undesirable effects: nausea, ataxia, dizziness, hypersensitivity, sedation