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Epilepsy & Anti-Epileptic Drugs (AEDs) - Simplified
What is a Seizure?
Neurons in the brain become over-excited and fire abnormally. To stop seizures, all AEDs work by depressing brain activity - either by calming things down (GABA up) or reducing the "fire" signal (Glutamate, Na+, Ca2+ blocked).
The 5 Core Mechanisms of AEDs
Think of the brain like a crowded, noisy room. Seizures = everyone screaming. AEDs are the "bouncers":
| Mechanism | What it does | Simple analogy |
|---|---|---|
| GABA ↑ | Increase the brain's "calm-down" chemical | Turn up the volume on silence |
| Glutamate ↓ | Reduce the brain's "excite" chemical | Turn off the megaphone |
| Na+ channel block | Stop the electrical signal from spreading | Cut the power cord |
| Ca2+ channel block | Prevent neuron activation at the start | Block the ignition key |
| K+ channel open | Stabilize the neuron at rest | Keep the brake on |
Group 1: Drugs that Increase GABA
Pregabalin / Gabapentin
- Release GABA (the brain's natural calming signal)
- Main use: Neuropathic pain (diabetic neuropathy, post-herpetic neuralgia)
- Recent finding: they mainly work by blocking Ca2+ channels
Vigabatrin
- Blocks the enzyme that breaks down GABA (so GABA accumulates)
- Side effect: Visual field contraction (tunnel vision) - important to remember
- Special use: Drug of choice for infantile spasm with Tuberous Sclerosis
- (ACTH is DOC for regular infantile spasm)
Tiagabine
- Blocks GABA reuptake transporter (GAT-1) so GABA stays longer in the synapse
Benzodiazepines (BZDs) & Barbiturates
These also enhance GABA. Think of them as "turbocharging" the GABA receptor.
| Drug | Drug of Choice (DOC) for |
|---|---|
| Diazepam | Febrile seizures |
| Lorazepam | Status epilepticus (1st line) |
| Clonazepam | Absence seizures |
| Clobazam | Lennox-Gastaut syndrome |
| Phenobarbitone | General use (causes hyperkinesia in children) |
Group 2: Drugs that Decrease Glutamate
| Drug | Blocks | Note |
|---|---|---|
| Felbamate | NMDA receptor | Side effect: bone marrow suppression (serious!) |
| Perampanel | AMPA receptor | Used in focal seizures |
Group 3: T-type Ca2+ Channel Blockers
Ethosuximide
- Only used for absence seizures (the "blank stare" episodes)
- NOT used for any other seizure type
Group 4: Na+ Channel Blockers (Big 3)
These block the electrical "spark" from spreading through neurons.
Phenytoin
- MOA: Blocks voltage-gated Na+ channels
- Follows zero-order kinetics (small dose increase = big blood level jump - dangerous!)
- Enzyme inducer (speeds up metabolism of other drugs)
- AVOID in: Absence & myoclonic seizures
- USE in: GTCS (grand mal), focal seizures, ventricular arrhythmias (Digoxin toxicity)
Side effects - mnemonic "HOT MALIKA":
| Letter | Side Effect |
|---|---|
| H | Hirsutism (excess hair), Hypertrophy of gums |
| O | Osteomalacia |
| T | Teratogenicity (Fetal Hydantoin syndrome) |
| M | Megaloblastic anemia (due to ↓ folate) |
| A | Arrhythmia (only in overdose) |
| L | Lymph node enlargement |
| I | ↓ Insulin |
| K | ↓ Vitamin K (newborn needs Vit K supplementation if mother on phenytoin) |
Carbamazepine (CBZ)
- MOA: Stabilizes hyperexcited neuronal membranes
- DOC: Focal seizures, Trigeminal neuralgia
- Also used in: Bipolar disorder, Diabetes Insipidus (but DESMOPRESSIN is actual DOC for DI)
- Avoid in elderly (causes hyponatremia)
Side effects - mnemonic "4A":
| Side Effect | |
|---|---|
| Auto-induction | Increases its own metabolism - dose needs to be raised over time |
| Aplastic Anemia | Bone marrow suppression |
| ADH release | Causes SIADH → Dilutional hyponatremia (↓Na+) → dangerous in elderly |
| Ataxia/Nystagmus | Cerebellar symptoms only at overdose |
- DOC for focal seizures in elderly = Lamotrigine (because CBZ causes hyponatremia in elderly)
Oxcarbazepine
- Similar to carbamazepine but fewer side effects
Group 5: K+ Channel Opener
Retigabine (Ezogabine)
- Opens K+ channels to stabilize neurons
- Used for focal seizures
- Does NOT act on GABA
The Star Drug: Sodium Valproate
Valproate is the "Swiss Army knife" of epilepsy - it has ALL 4 mechanisms:
- Blocks Na+ channels
- Blocks Ca2+ channels
- Increases GABA
- Decreases glutamate
Because it works on everything, it is the broadest spectrum AED.
DOC for: GTCS, Absence, Myoclonic, Atonic seizures, Lennox-Gastaut syndrome, Bipolar disorder
Side effects - mnemonic "VALPROATE":
| Letter | Side Effect |
|---|---|
| V | Vomiting |
| A | Alopecia (hair loss) / Curling of hair |
| L | Liver toxicity (hepatotoxicity - high in young children) |
| P | Pancreatitis, ↑ risk of PCOD (in women) |
| R | Rash/allergy |
| O | Obesity (weight gain) |
| A | Ataxia (at overdose) |
| TE | TEratogenicity - MOST teratogenic AED - causes neural tube defects |
Other Important Drugs
Topiramate
- Additional uses beyond seizures: ↓ alcohol craving, obesity, migraine prevention, bipolar disorder
- Side effect: Renal stones (shared with Zonisamide)
Lacosamide / Rufinamide
- Used in focal seizures
Lamotrigine
- DOC for focal seizures in elderly (safe, no hyponatremia)
- Works by: blocking Na+ channels + increasing GABA + decreasing glutamate
- Serious skin side effects:
- Steven Johnson Syndrome (skin surface <30% affected)
- Toxic Epidermal Necrolysis (skin surface >30% - more severe)
Newer AEDs
| Drug | Mechanism | Use |
|---|---|---|
| Levetiracetam / Brivaracetam | Bind to SV2A protein on synaptic vesicles | Broad use |
| Cannabidiol | Stimulates CB-1 receptors | Dravet syndrome |
| Stiripentol | Increases GABA + inhibits LDH | Dravet syndrome |
Epilepsy in Pregnancy - Key Points
| Situation | What to do |
|---|---|
| Already on AED (including valproate) | Don't stop it - add high-dose folic acid (4000 mcg/day) |
| First time epilepsy diagnosed in pregnancy | Prefer Levetiracetam or Lamotrigine |
| Most teratogenic AED | Valproate (avoid if possible) |
| Least teratogenic AEDs | Lamotrigine, Levetiracetam |
| Eclampsia (seizure due to high BP) | MgSO4 IV is DOC (neuroprotective) |
Status Epilepticus - Emergency Protocol
Definition: Seizure lasting >5 minutes, OR 2+ seizures without regaining consciousness in between.
This is a neurological emergency. Treat in steps:
1st Line (Stop the seizure NOW):
→ IV Lorazepam (DOC)
→ IV Diazepam (alternative)
2nd Line (Prevent it coming back):
→ IV Phenytoin or Fosphenytoin
3rd Line (If still seizing):
→ IV Sodium Valproate
→ Levetiracetam
→ Phenobarbitone
Refractory (Still not stopping - ICU):
→ Midazolam infusion
→ Propofol
→ Thiopentone
General Principles of AED Therapy (Your Handwritten Notes)
- Establish correct diagnosis and identify seizure type first
- Choose the right AED for that seizure type
- Start with monotherapy (one drug)
- Start with a low dose
- Ensure regular drug intake (don't skip doses)
- Monitor efficacy and adverse effects
- If monotherapy fails, switch to another drug
- Never stop abruptly - always taper (sudden withdrawal can trigger seizures!)
Quick "Which Drug for Which Seizure" Summary
| Seizure Type | DOC |
|---|---|
| Absence | Ethosuximide / Sodium Valproate |
| Febrile | Diazepam |
| Status Epilepticus | IV Lorazepam |
| GTCS | Sodium Valproate / Phenytoin |
| Focal | Carbamazepine / Lamotrigine (elderly) |
| Myoclonic | Sodium Valproate |
| Infantile Spasm | ACTH (Vigabatrin if Tuberous Sclerosis) |
| Lennox-Gastaut | Clobazam / Sodium Valproate |
| Trigeminal Neuralgia | Carbamazepine |
| Dravet Syndrome | Cannabidiol / Stiripentol |
Short and simplfy
Epilepsy & AEDs - Quick Summary
The Big Idea
Seizure = brain over-fires. AEDs = calm it down by:
- ↑ GABA (brake) | ↓ Glutamate (accelerator) | Block Na+, Ca2+ | Open K+
5 Drug Groups
1. GABA Boosters
| Drug | Key Point |
|---|---|
| Pregabalin/Gabapentin | DOC neuropathic pain |
| Vigabatrin | Side effect = tunnel vision; DOC infantile spasm + Tuberous Sclerosis |
| Tiagabine | Blocks GABA reuptake |
| BZDs (Diazepam/Lorazepam/Clonazepam/Clobazam) | See table below |
| Phenobarbitone | Causes hyperkinesia in kids |
2. Glutamate Blockers
- Felbamate - blocks NMDA → causes bone marrow suppression
- Perampanel - blocks AMPA → used in focal seizures
3. T-type Ca2+ Blocker
- Ethosuximide - ONLY for absence seizures, nothing else
4. Na+ Channel Blockers
- Phenytoin, Carbamazepine, Oxcarbazepine
- Use in GTCS + focal. Avoid in absence + myoclonic
5. K+ Channel Opener
- Retigabine - focal seizures only
Star Drug: Sodium Valproate
- Has ALL 4 mechanisms = broadest spectrum
- DOC for: GTCS, Absence, Myoclonic, Atonic, Lennox-Gastaut, Bipolar
- Side effects: VALPROATE (Vomiting, Alopecia, Liver toxicity, Pancreatitis/PCOD, Rash, Obesity, Ataxia, TEratogenic)
Key Drug Details
Phenytoin side effects - HOT MALIKA:
Hirsutism/gum hypertrophy, Osteomalacia, Teratogenicity, Megaloblastic anemia, Arrhythmia (OD), Lymph nodes, ↓Insulin, ↓Vit K
Carbamazepine side effects - 4A:
Auto-induction, Aplastic anemia, ADH↑ (hyponatremia), Ataxia (OD)
- Avoid in elderly (hyponatremia) → use Lamotrigine instead
Lamotrigine:
- DOC focal seizures in elderly
- Serious skin side effect: Stevens-Johnson Syndrome / TEN
Which Drug for Which Seizure
| Seizure | DOC |
|---|---|
| Absence | Ethosuximide / Valproate |
| Febrile | Diazepam |
| Status epilepticus | IV Lorazepam |
| GTCS / Focal | Valproate / Carbamazepine |
| Myoclonic | Valproate |
| Infantile spasm | ACTH (Vigabatrin if Tuberous Sclerosis) |
| Lennox-Gastaut | Clobazam |
| Trigeminal neuralgia | Carbamazepine |
| Dravet syndrome | Cannabidiol / Stiripentol |
Status Epilepticus (Emergency)
Seizure >5 min or 2+ seizures without waking up
- 1st line → IV Lorazepam (DOC) / Diazepam
- 2nd line → IV Phenytoin / Fosphenytoin
- 3rd line → IV Valproate, Levetiracetam, Phenobarbitone
- Refractory → ICU: Midazolam, Propofol, Thiopentone
Pregnancy
- Most teratogenic = Valproate | Least = Lamotrigine, Levetiracetam
- Already on AED? Don't stop - add folic acid 4000 mcg/day
- First time in pregnancy? Use Lamotrigine or Levetiracetam
- Eclampsia seizures? MgSO4 IV
Golden Rules
- Start with monotherapy at low dose
- Never stop abruptly (triggers rebound seizures)
- Monitor regularly
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