A/32. Antiepileptics used in partial seizures and generalized tonic-clonic seizures except for the “broad spectrum” agents

Question 1

Drugs need to know in this topic

Answer 1

phenytoin

carbamazepine

phenobarbital

vigabatrine

Question 2

Potential mechanisms of action

Answer 2

1.Decrease axonal conduction by preventing Na+ influx (through inhibition of fast Na+ channels) Effect is rate dependent (only inactivated channels are inhibited), results in prolongation of the inactivated state of the channel and the refractory period of the neuron

1. Phenytoin
2. Carbamazepine
3. Valproic acid (only at high doses)

2. Enhance the inhibitory tone by facilitation of GABA-mediated hyperpolarization

1. Barbiturates
2. Benzodiazepines

3. Reduce excitatory effects of glutamate

1. Lamotrigine
2. Topiramate
3. Felbamate

4. Decrease presynaptic Ca2+ influx via inhibition of T-type channels in thalamic neurons

1. Ethosuximide
2. Valproic acid

Question 3

Classification of seizures

Answer 3

1. Tonic-clonic seizure (‘grand mal’)
2. Absence seizure (‘petit mal’)
3. Myoclonic seizure
4. Status epilepticus
5. Generalized seizure
6. Partial (focal) seizure

Question 4

Characteristics of Seizures and its drug of choice

1. Tonic-clonic seizure (‘grand mal’)

Answer 4

Consists of bilateral symmetric convulsive movements of all limbs, with impairment of
consciousness
1. Tonic phase (< 1 min’) → loss of consciousness, muscle stiffening
2. Clonic phase (2-3 min’) → jerking of body muscles

1. Valproic acid
2. Phenytoin
3. Carbamazepine
4. Lamotrigine

Question 5

Characteristics of Seizures and its drug of choice

2. Absence seizure (‘petit mal’)

Answer 5

Impaired consciousness (often abrupt onset and brief), starts with unresponsiveness to 
external verbal stimuli, sometimes with eye blinking or head nodding

1. Ethosuximide
2. Clonazepam (benzodiazepine)
3. Valproic acid

Question 6

Characteristics of Seizures and its drug of choice

3. Myoclonic seizure

Answer 6

rapidly alternating contraction and relaxation jerking or twitching of a muscle

1. Clonazepam
2. Lamotrigine
3. Valproic acid

Question 7

Characteristics of Seizures and its drug of choice

4. Status epilepticus

Answer 7

Continuous seizure lasting more than 5 min’, or ≥ 2 seizures without full recovery of
consciousness between any of them
Life-threatening, medical emergency

1. Lorazepam
2. Diazepam
3. Phenytoin, Fosphenytoin
4. Phenobarbital
   *In severe cases that does not respond to anticonvulsants,
   general anesthesia may be induced

Question 8

Characteristics of Seizures and its drug of choice

5. Generalized seizure

Answer 8

1. Involves the whole brain at onset
2. Loss of consciousness

Question 9

Characteristics of Seizures and its drug of choice

6. Partial (focal) seizure

Answer 9

Involves focal cortical region at onset

1. Simple partial seizure → no loss of consciousness
2. Complex partial seizure → loss of consciousness or impaired awareness during the seizure

Question 10

General features of anticonvulsants

Answer 10

• *1.CNS depressant effect** – additive with other CNS depressants (benzodiazepines, barbiturates, opioids, anesthesia)
• *2.Abrupt withdrawal of anticonvulsant agent may precipitate acute seizures** – risk to develop status epilepticus
• *3.Extensive drug-drug interactions** (phenytoin and carbamazepine → induce cytochrome P450; valproic acid → inhibits cytochrome P450)
• *4.Efficacy of oral contraceptives ↓** (not seen with valproic acid)
• *5.Extensive teratogenicity of most drugs in the group**

Question 11

Phenobarbital

Answer 11

is the drug of choice to control seizures during pregnancy Considered as the safest anticonvulsant due to its high plasma protein binding (less free fraction of the drug can cross the placental barrier and affect the fetus)

∙↑of the inhibitory actions of GABA

Oral, IV

1. Seizures (not 1st-line agent)

Question 12

Phenytoin

Answer 12

Inhibition of axonal Na+ channels
Prevent seizure propagation, but not initiation

Oral, IV

Inducer of cytochrome P450 enzymes

1. Tonic-clonic seizures (widely-used); not effective in absence seizures
2. Status epilepticus (IV)

SEs

∙Neurologic (nystagmus, dizziness, ataxia, diplopia)

∙gingival hyperplasia

∙teratogenic

Question 13

Carbamazepine

Answer 13

Inhibition of axonal Na+ channels

Prevent seizure propagation, but not initiation

Oral

Inducer of cytochrome P450 enzymes

1. Tonic-clonic (generalized) seizures
2. Partial seizures
3. Trigeminal neuralgia (1st-line)
4. Bipolar disorders

SEs

∙Neurologic (diplopia and ataxia)

Question 14

vigabatrin

Answer 14

1. Inhibits GABA transaminase irreversibly → ↑ GABA
2. Refractory focal seizures (adjunctive therapy)
3. Monotherapy for infantile spasms (West syndrome)

SEs

1. Irreversible vision loss