Mention the classification and uses of antiepileptic drugs
Mbbs 2nd yr refer kdt
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Antiepileptic (Antiseizure) Drugs — Classification & Uses
(Based on Katzung's Basic & Clinical Pharmacology 16e and Goodman & Gilman's Pharmacological Basis of Therapeutics)
Seizure Classification (ILAE)
Before classifying drugs, it helps to know what seizure types they treat:
| Category | Types |
|---|---|
| Focal onset | Focal aware (simple partial), Focal impaired awareness (complex partial), Focal-to-bilateral tonic-clonic (secondarily generalized) |
| Generalized onset | Tonic-clonic (grand mal), Absence (petit mal), Myoclonic, Atonic (drop attacks), Epileptic spasms (West syndrome) |
| Special syndromes | Lennox-Gastaut syndrome, Dravet syndrome, Juvenile myoclonic epilepsy (JME) |
Classification of Antiepileptic Drugs
I. By Chemical Class / Drug Families
1. Hydantoins
- Phenytoin (diphenylhydantoin)
- Fosphenytoin (prodrug of phenytoin)
2. Barbiturates
- Phenobarbital
- Primidone (metabolized to phenobarbital)
- Mephobarbital
3. Iminostilbenes (Dibenzazepines)
- Carbamazepine
- Oxcarbazepine
- Eslicarbazepine
4. Succinimides
- Ethosuximide
- Methsuximide
5. Benzodiazepines
- Diazepam, Lorazepam (IV — status epilepticus)
- Clonazepam, Clobazam (chronic use)
- Midazolam
6. Valproic Acid (Valproate)
- Sodium valproate / valproic acid / divalproex sodium
7. Newer / Second-generation Drugs
- Lamotrigine — phenyltriazine
- Levetiracetam — pyrrolidine
- Topiramate — sulfamate-substituted monosaccharide
- Gabapentin — structural GABA analogue
- Pregabalin — structural GABA analogue
- Zonisamide — sulfonamide benzisoxazole
- Lacosamide — functionalized amino acid
- Vigabatrin — GABA analogue
- Tiagabine — nipecotic acid derivative
- Felbamate
- Perampanel
- Brivaracetam
- Rufinamide
- Stiripentol
8. Carbonic Anhydrase Inhibitors
- Acetazolamide (adjunct, especially menstrual seizures)
9. Others
- Cannabidiol (Epidiolex) — Dravet/Lennox-Gastaut
- Fenfluramine — Dravet syndrome
- Everolimus — TSC-related seizures
- ACTH / Corticosteroids — infantile spasms
II. By Mechanism of Action
| Mechanism | Drugs |
|---|---|
| Na⁺ channel blockade (slow inactivation) | Phenytoin, Carbamazepine, Oxcarbazepine, Lamotrigine, Topiramate, Zonisamide, Lacosamide, Valproate |
| GABA-A receptor enhancement | Benzodiazepines, Barbiturates, Topiramate, Felbamate |
| GABA reuptake inhibition | Tiagabine |
| GABA transaminase inhibition | Vigabatrin |
| T-type Ca²⁺ channel blockade | Ethosuximide, Valproate |
| Synaptic vesicle protein SV2A modulation | Levetiracetam, Brivaracetam |
| α₂δ subunit Ca²⁺ channel binding | Gabapentin, Pregabalin |
| AMPA receptor antagonism | Perampanel |
| Carbonic anhydrase inhibition | Acetazolamide, Topiramate, Zonisamide |
Uses of Major Antiepileptic Drugs
1. Phenytoin
- Drug of choice (older): Focal seizures, focal-to-bilateral tonic-clonic seizures
- IV (fosphenytoin): Status epilepticus (2nd line after benzodiazepines)
- Also used: Trigeminal neuralgia, cardiac arrhythmias (class IB)
- Not used in: Absence seizures (may worsen)
2. Carbamazepine
- Drug of choice: Focal seizures, focal-to-bilateral tonic-clonic seizures
- Also: Trigeminal neuralgia (DOC), bipolar disorder (mood stabilizer), diabetic neuropathy
- Not used in: Absence, myoclonic seizures (may worsen)
3. Valproic Acid (Valproate)
- Broad-spectrum — drug of choice for:
- Generalized tonic-clonic seizures
- Absence seizures
- Myoclonic seizures (including JME)
- Mixed seizure disorders
- Also used: Bipolar disorder, migraine prophylaxis
- Avoid in: Pregnancy (teratogenic — neural tube defects), liver disease
4. Ethosuximide
- Drug of choice: Typical absence seizures (petit mal) — especially in children
- Not effective: Focal seizures or tonic-clonic seizures
- If absence + tonic-clonic coexist: Use valproate instead
5. Phenobarbital
- Drug of choice in neonatal seizures
- Used in febrile convulsions (prophylaxis)
- Broad-spectrum but causes sedation; now second-line for most seizures
- Cheap and widely available in low-resource settings
6. Benzodiazepines
| Drug | Use |
|---|---|
| Diazepam IV/rectal | Acute status epilepticus (first-line) |
| Lorazepam IV | Preferred for status epilepticus (longer duration) |
| Midazolam | IM/intranasal for out-of-hospital status epilepticus |
| Clonazepam | Myoclonic seizures, atonic seizures, infantile spasms |
| Clobazam | Adjunct in Lennox-Gastaut syndrome |
7. Lamotrigine
- Broad-spectrum; effective in focal seizures, generalized tonic-clonic, absence, atypical absence, atonic, JME
- Drug of choice in women of childbearing age (relatively safer in pregnancy)
- Preferred in Lennox-Gastaut syndrome (adjunct)
- Risk: Stevens-Johnson syndrome (especially if titrated rapidly or combined with valproate)
8. Levetiracetam
- Very broad-spectrum: focal seizures, generalized tonic-clonic, myoclonic, absence
- Increasingly used as first-line (monotherapy and adjunct)
- Good safety profile; minimal drug interactions
- Main SE: behavioral/psychiatric effects (irritability, aggression)
- Available IV — used in status epilepticus
9. Topiramate
- Broad-spectrum: focal, generalized tonic-clonic, Lennox-Gastaut, JME, infantile spasms, Dravet
- Also approved: Migraine prophylaxis, obesity
- SE: cognitive slowing, word-finding difficulty ("dopamax"), weight loss, kidney stones, metabolic acidosis, glaucoma
10. Gabapentin & Pregabalin
- Gabapentin: Adjunct for focal seizures; also used in neuropathic pain, postherpetic neuralgia
- Pregabalin: Adjunct for focal seizures; also anxiety, fibromyalgia, neuropathic pain
- Neither is useful for generalized seizures
11. Zonisamide
- Broad-spectrum: focal seizures, generalized tonic-clonic, myoclonic
- Also used adjunctively in infantile spasms
- SE: cognitive effects, weight loss, oligohidrosis (children), kidney stones
12. Lacosamide
- Adjunct for focal seizures
- Unique MOA: enhances slow inactivation of Na⁺ channels
- Also IV formulation available
13. Vigabatrin
- Drug of choice: Infantile spasms (especially due to tuberous sclerosis)
- Adjunct for refractory focal seizures
- Serious SE: irreversible visual field defects (limits use)
14. Tiagabine
- Adjunct for focal seizures
- Rarely used due to narrow spectrum and risk of non-convulsive status epilepticus
15. Acetazolamide
- Adjunct; especially for catamenial epilepsy (menstrual seizure exacerbations)
- Tolerance develops rapidly; not suitable for chronic therapy
16. Cannabidiol (CBD / Epidiolex)
- Approved for: Dravet syndrome, Lennox-Gastaut syndrome, TSC-related seizures
- Mechanism: uncertain (not via cannabinoid receptors at therapeutic doses)
Drug Selection by Seizure Type (Summary Table)
| Seizure Type | First-line | Alternatives |
|---|---|---|
| Focal (simple/complex partial) | Carbamazepine, Lamotrigine, Levetiracetam | Oxcarbazepine, Phenytoin, Valproate, Topiramate |
| Focal-to-bilateral tonic-clonic | Carbamazepine, Lamotrigine, Levetiracetam | Phenytoin, Valproate |
| Generalized tonic-clonic | Valproate, Lamotrigine, Levetiracetam | Topiramate, Carbamazepine |
| Typical absence | Ethosuximide, Valproate | Lamotrigine |
| Myoclonic | Valproate, Levetiracetam, Clonazepam | Topiramate, Zonisamide |
| Atonic / LGS | Valproate, Clobazam, Lamotrigine | Rufinamide, Felbamate, Topiramate |
| Infantile spasms | ACTH, Vigabatrin | Prednisolone, Clonazepam |
| JME | Valproate | Levetiracetam, Lamotrigine, Topiramate |
| Status epilepticus | Lorazepam/Diazepam IV → Fosphenytoin/Levetiracetam IV | Phenobarbital, Midazolam, Propofol |
Important Non-Epilepsy Uses
| Drug | Non-epilepsy use |
|---|---|
| Carbamazepine | Trigeminal neuralgia (DOC), bipolar disorder |
| Valproate | Bipolar disorder, migraine prophylaxis |
| Phenytoin | Cardiac arrhythmia (digoxin-induced), trigeminal neuralgia |
| Gabapentin/Pregabalin | Neuropathic pain, PHN, anxiety, fibromyalgia |
| Topiramate | Migraine prophylaxis, obesity |
| Lamotrigine | Bipolar disorder (maintenance) |
| Clonazepam | Anxiety disorders, panic disorder |
| Phenobarbital | Neonatal jaundice (enzyme induction) |
Sources: Katzung's Basic and Clinical Pharmacology, 16th Ed. (Chapter 24); Goodman & Gilman's Pharmacological Basis of Therapeutics (Chapter 20) — the closest equivalents to KDT available in the library.
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