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💊 Epilepsy Drugs — Complete Easy Guide

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🧠 Why Are These Drugs Needed?

1. Reducing neuronal excitation — blocking sodium or calcium channels
2. Enhancing inhibition — boosting GABA (the brain's "brake" chemical)
3. Blocking glutamate — reducing the brain's main "accelerator"

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📋 Quick Classification

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💉 Individual Drug Profiles

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1. 🔶 Valproic Acid (Valproate)

• Mechanism: Multiple — GABA potentiation + sodium channel block + T-type Ca²⁺ block + NMDA inhibition
• Used for: ALL seizure types — focal, generalized, absence, myoclonic
• Side effects: Weight gain, hair loss, tremor, liver toxicity (especially in children <2 years), pancreatitis
• ⚠️ Pregnancy: Highly teratogenic — avoid in women of childbearing age (neural tube defects, cognitive impairment in offspring). Virtually absent in breast milk (safe for breastfeeding)
• Special: Drug of choice for juvenile myoclonic epilepsy

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2. 🔷 Phenytoin (Dilantin)

• Mechanism: Sodium channel blocker — stabilizes inactive state of Na⁺ channels
• Used for: Focal and generalized tonic-clonic seizures, status epilepticus (IV form)
• Side effects: Gum overgrowth (gingival hyperplasia), hirsutism, facial coarsening, cerebellar atrophy with long-term use, rash
• ⚠️ Tricky pharmacokinetics: Zero-order (non-linear) — small dose changes cause big blood level changes → narrow therapeutic window
• Drug interactions: Hepatic enzyme INDUCER — reduces levels of many other drugs
• HLA warning: HLA-B*1502 (Asian ancestry) → risk of Stevens-Johnson syndrome

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3. 🔷 Carbamazepine (Tegretol)

• Mechanism: Sodium channel blocker
• Used for: Focal seizures, generalized tonic-clonic; also trigeminal neuralgia and bipolar disorder
• Side effects: Diplopia, dizziness, ataxia, hyponatremia (SIADH), rash, blood dyscrasias
• ⚠️ Cross-reactivity: High cross-reactivity with phenytoin and phenobarbital for skin reactions
• Enzyme inducer: Speeds up metabolism of many drugs (including its own!)
• In breast milk: 40% of maternal serum level — considered relatively safe

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4. 🔷 Oxcarbazepine / Eslicarbazepine

• Mechanism: Sodium channel blocker (similar to carbamazepine)
• Used for: Focal seizures
• Advantage over carbamazepine: Less drug interactions, better tolerated
• Side effects: Hyponatremia (more than carbamazepine), dizziness, rash

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5. 🟢 Lamotrigine (Lamictal)

• Mechanism: Sodium channel blocker
• Used for: Focal and generalized seizures, absence seizures
• Side effects: Serious rash — Stevens-Johnson syndrome (especially if titrated too fast)
• Rule: Start LOW, go SLOW with dose titration
• Pregnancy: Relatively preferred over valproate for women of childbearing age
• Enzyme inducer — interactions with other AEDs

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6. 🟢 Levetiracetam (Keppra)

• Mechanism: SV2A protein modulation (synaptic vesicle release)
• Used for: Focal and generalized seizures — very broad spectrum
• Advantages: Minimal drug interactions, renal excretion (no liver concerns), no enzyme induction
• Side effects: Mood disturbance, irritability, psychosis (most important limitation)
• Pregnancy: Switch from valproate to levetiracetam is often recommended for women with juvenile myoclonic epilepsy planning pregnancy

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7. 🟢 Brivaracetam (Briviact)

• Mechanism: SV2A modulation (like levetiracetam but higher affinity)
• Used for: Focal and generalized seizures
• Advantage: Less psychiatric side effects than levetiracetam

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8. 🟡 Phenobarbital

• Mechanism: GABA-A receptor potentiation (increases Cl⁻ channel opening duration)
• Used for: Focal and generalized seizures, neonatal seizures
• Side effects: Sedation, cognitive impairment, dependence
• ⚠️ Breast milk: High concentration → sedates newborns (risky for breastfeeding)
• Enzyme inducer: Major interactions

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9. 🟡 Topiramate (Topamax)

• Mechanism: Multiple — GABA potentiation + AMPA/kainate glutamate block + Na⁺ channel block + Ca²⁺ block
• Used for: Focal and generalized seizures; also migraine prevention, obesity
• Side effects: Cognitive impairment ("Dopamax"), word-finding difficulty, kidney stones (nephrolithiasis), weight loss, metabolic acidosis
• Also used in: Status epilepticus (refractory)

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10. 🟡 Ethosuximide (Zarontin)

• Mechanism: T-type calcium channel blocker
• Used for: Absence seizures (petit mal) ONLY
• Side effects: GI upset, hiccups, insomnia
• Important: Does NOT work for tonic-clonic or focal seizures — very narrow indication

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11. 🟡 Gabapentin / Pregabalin

• Mechanism: Binds α2δ subunit of voltage-gated Ca²⁺ channels → reduces Ca²⁺ influx
• Gabapentin used for: Adjunctive focal seizures, neuropathic pain, postherpetic neuralgia
• Pregabalin used for: Adjunctive focal seizures, neuropathic pain, fibromyalgia, anxiety
• Side effects (both): Sedation, dizziness, peripheral edema, weight gain (pregabalin > gabapentin)
• Advantage: No hepatic metabolism, no drug interactions

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12. 🔴 Benzodiazepines (Diazepam, Lorazepam, Clonazepam, Midazolam)

• Mechanism: GABA-A receptor potentiation (increase frequency of Cl⁻ channel opening)
• Primary use: EMERGENCY treatment — status epilepticus (lorazepam/diazepam IV is first-line)
• Clonazepam: Long-term adjunctive use for myoclonic seizures
• Side effects: Sedation, respiratory depression, tolerance, dependence
• ⚠️ Breast milk: High levels — sedation risk for newborns

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13. 🔵 Lacosamide (Vimpat)

• Mechanism: Slow inactivation of Na⁺ channels (unique mechanism — different from other Na blockers)
• Used for: Focal and generalized seizures
• Side effects: Dizziness, diplopia, PR interval prolongation (cardiac monitoring if pre-existing conduction issues)

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14. 🔵 Zonisamide (Zonegran)

• Mechanism: Na⁺ channel block + T-type Ca²⁺ block (similar profile to topiramate)
• Used for: Focal and generalized seizures
• Side effects: Kidney stones, cognitive impairment, weight loss (similar to topiramate)
• Also: Sulfonamide derivative — contraindicated if sulfa allergy

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15. 🔵 Vigabatrin (Sabril)

• Mechanism: Irreversible GABA transaminase inhibitor → increases GABA levels
• Used for: Infantile spasms (West syndrome — first-line), refractory focal seizures
• ⚠️ Major side effect: Permanent visual field defects (retinal toxicity) — requires regular ophthalmology monitoring

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16. 🔵 Perampanel (Fycompa)

• Mechanism: AMPA glutamate receptor antagonist (unique class)
• Used for: Focal and generalized seizures (adjunctive)
• Side effects: Dizziness, aggression/hostility, psychiatric symptoms

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⚡ Status Epilepticus Treatment (Emergency)

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🤰 Epilepsy Drugs in Pregnancy

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🧬 Key Skin Reaction Warning

• Maculopapular rash (common, usually resolves on stopping)
• Stevens-Johnson syndrome / Toxic Epidermal Necrolysis (life-threatening)
• High cross-reactivity between this group — if one causes rash, avoid all aromatics

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🔑 Memory Tricks

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📊 Summary at a Glance

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💉 Thiopentone Sodium — Complete Guide

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🧪 Chemical Identity

Chemical Structure

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⚙️ Mechanism of Action

1. GABA-A Receptor Potentiation (Primary)

• Binds to GABA-A receptor (a Cl⁻ ion channel)
• At low concentrations: Enhances GABA's effect → increases duration of Cl⁻ channel opening → hyperpolarization → sedation/hypnosis
• At higher concentrations: Acts as GABA mimetic itself — opens Cl⁻ channels even without GABA → produces full anesthesia
• Net result: Increased Cl⁻ conductance → hyperpolarized neuron → raised threshold for firing

2. Inhibition of Excitatory Transmission (Secondary)

• Blocks glutamate (NMDA-gated currents) in a concentration-dependent manner
• Decreases extracellular glutamate levels in the CNS
• Also reduces acetylcholine synaptic transmission

Key point: Unlike benzodiazepines (which only increase frequency of Cl⁻ channel opening), barbiturates also increase the duration of opening AND can directly activate channels at high doses.

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💊 Pharmacokinetics

Distribution & Redistribution

Key Pharmacokinetic Values

Metabolism

• Hepatic — by 4 processes:
  1. Oxidation at C5 (most important) → polar metabolites excreted in urine
  2. N-dealkylation
  3. Desulfuration at C2 (removes the sulfur)
  4. Destruction of barbituric acid ring (minor)
• Metabolites are inactive, water-soluble → excreted in urine/bile
• NOT significantly altered by liver cirrhosis (unusually — liver clearance preserved)
• In large doses (300–600 mg/kg): switches from first-order → zero-order kinetics (Michaelis-Menten saturation)

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🏥 Clinical Uses & Dosage

• Unconsciousness occurs in < 30 seconds
• Patients may notice a garlic or onion taste after injection
• ⚠️ DO NOT mix with depolarizing or non-depolarizing muscle relaxants in the same syringe — precipitation of insoluble thiopentone acid occurs (very different pH)

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🫀 Organ System Effects

CNS Effects

Note: ICP decreases more than MAP after thiopental, preserving cerebral perfusion pressure (CPP = MAP − ICP). This is why it is useful in neurosurgery.

Cardiovascular Effects

• ↓ Blood pressure — primarily from peripheral vasodilation
• Negative inotrope — direct depression of cardiac contractility
• Baroreceptor reflex less inhibited than with propofol → compensatory ↑ heart rate limits hypotension
• ⚠️ More dangerous in: hypovolemia, cardiac tamponade, cardiomyopathy, coronary artery disease — these patients cannot compensate for vasodilation
• Hypotension worsened by: large doses, rapid injection rate

Respiratory Effects

• Respiratory depressant — typical induction dose causes transient apnea
• ↓ Tidal volume + ↓ respiratory rate → ↓ minute ventilation
• ↓ Ventilatory response to hypercapnia and hypoxia
• Laryngeal and cough reflexes less suppressed than propofol → inferior choice for airway instrumentation without muscle relaxants
• Risk of laryngospasm or bronchospasm if airway stimulated during light anesthesia

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⚠️ Adverse Effects & Complications

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🚫 Contraindications

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🔬 Structure–Activity Relationship

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🔄 Thiopentone vs. Propofol (Key Comparison)

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🧠 Memory Summary

THIOPENTONE = "The GABA GAP Closer"

G — GABA potentiation (prolongs Cl⁻ channel opening)
A — Anesthesia induction (3–5 mg/kg IV)
B — Brain protective (↓ ICP, ↓ CMRO2)
A — Apnea + Apnoea risk

G — Garlic/onion taste on injection
A — Avoid in Porphyria (ABSOLUTE contraindication)
P — Precipitation with muscle relaxants (pH mismatch)

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📊 Quick Reference Card

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