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1. Choice of Antiepileptic Drugs
Sunil Kumar Daha
(Patan Academy of Health
science-SoM, Nepal)

2. Definition
• Seizure: caused by an abnormal electrical discharge in the brain
• Epilepsy :tendency to have recurrent seizures

4. Prolongation of Na channel
inactivation
Facilitation of GABA
mediated Cl channel opening
Inhibition of ‘T’ type Ca
current
•Phenytoin
•Carbamazepine
•Valproate
•Lamotrigine
•Topiramate
•Zonisamide
•Barbiturate
•Benzodiazepine
•Vigabatrin
•Valproate
•Gabapentin
•Tiagabine
•Ethosuximide
•Trimethadione
•Valproate

6. Guidelines for anticonvulsant therapy
• Start with one first-line drug
• Start at a low dose; gradually increase dose until effective
• Optimise compliance (use minimum number of doses per
day)
• If first drug fails (seizures continue or side-effects develop),
start second first-line drug gradually withdrawing first

7. Contd..
• If second first line drug fails (seizures continue or side-effects develop),
start second-line drug in combination with preferred first-line drug at
maximum tolerated dose (beware of interactions)
• If this combination fails (seizures continue or side-effects develop),
replace second-line drug with alternative second line drug
• If this combination fails, check compliance and reconsider diagnosis (is
there an occult structural or metabolic lesion or seizures truly epileptic)

8. Contd..
• If this combination fails, consider alternative, non-drug treatments
(e.g. epilepsy surgery, vagal nerve stimulation)
• Do not use more than two drugs in combination at any one time

9. Adverse Effects of Commonly Used
Antiepileptic Drugs

10. Drugs Typical Dose Neurologic Systemic
Phenytoin (diphenyl-
hydantoin)
300–400 mg/d (3–6 mg/kg,
adult; 4–8 mg/kg, child); qd-
bid
Dizziness, Diplopia, Ataxia,
Incoordination, Confusion
Gum hyperplasia,
Lymphadenopathy, Hirsutism,
Osteomalacia, Facial
coarsening, Skin rash
Carbamazepine 600–1800 mg/d (15–35
mg/kg, child); bid-qid
Ataxia
Dizziness
Diplopia
Vertigo
Aplastic anemia
Leukopenia
Gastrointestinal irritation
Hepatotoxicity
Hyponatremia
Valproic acid 750–2000 mg/d (20–60
mg/kg); bid-qid
Ataxia
Sedation
Tremor
Hepatotoxicity
Thrombocytopenia
Gastrointestinal irritation
Weight gain
Transient alopecia
Hyperammonemia
Lamotrigine 150–500 mg/d; bid Dizziness
Diplopia
Sedation
Ataxia
Headache
Skin rash
Stevens-Johnson syndrome

11. Drugs Typical Dose Neurologic Systemic
Ethosuximide 750–1250 mg/d (20-40
mg/kg); qd-bid
Ataxia
Dizziness
Diplopia
Vertigo
Gastrointestinal irritation
Skin rash
Bone marrow suppression
Topiramate 200–400 mg/d; bid Psychomotor slowing
Sedation
Speech or language
problems
Fatigue
Paresthesias
Renal stones (avoid use
with other carbonic
anhydrase inhibitors)
Glaucoma
Weight loss
Phenobarbitone 60–180 mg/d; qd Sedation
Ataxia
Confusion
Dizziness
Decreased libido
Depression
Skin rash

12. Monitoring therapy
• Dose of anticonvulsant drug in an individual should be governed by the
efficacy of seizure control and development of side-effects rather than
blood levels alone
• With some drugs such as phenytoin and carbamazepine, occasional
measurement of the blood level can be a guide
• In case of sodium valproate: poor relationship between blood level and
anticonvulsant efficacy

13. Withdrawing anticonvulsant therapy
• After complete control of seizures for 2–4 years, withdrawal of
medication may be considered
• Withdrawal should be undertaken slowly, reducing the drug
dose gradually over 6–12 months
• Overall, the recurrence rate of seizures after drug withdrawal
is about 40%

14. Pregnancy
• Valproate, phenytoin, carbamazepine- folic acid deficiency,
• 400ug to prevent neural tube defect normally
• 5mg in epileptic
• Lamotrigine ,carbamazepine- given

15. References
• Davidson’s principle and practice of medicine, 21st edition
• Kumar and Clark’s Textbook of Internal Medicine, 8th edition
• Harrison’s Principle of Medicine, 18th edition

16. Thank you