M5: Antiseizure Drugs

Question 1

Treatment of Seizures

Answer 1

1. Non-Pharmacological:
   - Avoid precipitating factors (e.g., insomnia, alcohol consumption, stress, infection)
   - Safety precautions (e.g., driving, operating heavy machinery)
   - Diet control – ketogenic diet
   - Surgery
2. Pharmacological:
   Antiseizures = anticonvulsants = antiepileptic drugs

Question 1

Antiseizure Drugs
- Class and Mechanism of Action
- Pharmacokinetics
- Adverse Effects

Answer 1

• They control but do NOT cure seizures

Seizures Control:
- Complete control: ~50% of patients
- Partial control: ~25% of patients
- No control: ~25% of patients

CLASS AND MECHANISM OF ACTION:
1. Increase GABA activity in the brain →
Increase inhibitory input to the neuron → suppress firing
DRUGS = Benzodiazepines, Valproate, Phenobarbital

2. Block Na+ channel electrical activity →
   Block electrical activity of the nerve → slow the nerve impulses
   DRUGS = Phenytoin, Lamotrigine , Valproate
3. Decrease the release of glutamate at the synapse →
   Decrease excitatory transmission
   DRUGS = Lamotrigine

PHARMACOKINETICS:
1. GI absorption: 80-100%
2. Metabolism: liver (hydroxylation & conjugation)
3. Excretion: kidney

ADVERSE EFFECTS (dose-related):
1. CNS:
- Sedation
- Tremors & ataxia
- Cognitive & visual - impairment

2. Gastrointestinal:
   - Nausea, vomiting, and diarrhea
3. Liver:
   - Elevated liver enzymes:
   Generally asymptomatic (periodic monitoring of liver function)
4. Immune System:
   - Benign skin rashes (5–20%)
   - Severe, potentially fatal skin hypersensitivity reactions (not uncommon)
5. Weight Gain
6. Teratogenic Effect:
   - Cause neural tube defect
   - DRUG = valproate
   -. Prevention:
   Avoid during pregnancy
   Folic acid supplements

• Abrupt withdrawal may precipitate seizures

Question 2

How to Minimize Withdrawal Effects?

Answer 2

1. Monotherapy when possible
2. Start with a low dose →
3. Slowly increase the dose to reach target “Start Low, Go Slow”
4. Administer with meals
5. Divide the dose over the day

Question 3

Drug Interactions

Answer 3

Most anti seizures induce hepatic microsomal enzymes →
↑ metabolism of concurrently administered drugs →
↓ concurrent drugs’ therapeutic effect

To Minimize This:
1. Limit coadministration
2. Monitor response
3. Adjust the dose

Question 4

Overdose/Toxicity

Answer 4

1. Exaggeration of adverse effects
2. Most dangerous:
   - Respiratory depression
   Potentiated by other CNS depressants & alcohol
3. Treatment:
   Supportive measures