Broad vs Narrow AEDs
Broad-spectrum (focal & generalized): Levetiracetam, Valproate, Lamotrigine, Topiramate. Narrow-spectrum (focal only; WORSER absence): Carbamazepine, Phenytoin.
Parkinson Therapy
Levodopa (crosses BBB) + Carbidopa (peripheral dopa-decarboxylase inhibitor reduces nausea/arrhythmias); Entacapone (COMT inhibitor); Pramipexole (D2 agonist).
Local Anesthetics & LAST
Amides have 2 'i's (Lidocaine, Bupivacaine); Esters have 1 'i' (Procaine, Tetracaine). LAST: perioral numbness, seizures, cardiac arrest; treat with IV 20% Lipid Emulsion.
Malignant Hyperthermia
Triggered by Halothane/Sevoflurane or Succinylcholine; RYR1 mutation causing uncontrolled sarcoplasmic Ca2+ release; treat immediately with IV Dantrolene.
Antiepileptic Drugs: Mechanisms & High-Yield Board Adverse Effects
Mastering seizure pharmacotherapy requires understanding exact receptor mechanisms and high-yield idiosyncratic toxicities:
| Antiepileptic Agent | Primary Molecular Mechanism | Seizure Indications | High-Yield Board Toxicity / Board Trap |
|---|---|---|---|
| Levetiracetam (Keppra) | Binds synaptic vesicle protein SV2A → ↓ neurotransmitter release | Broad-spectrum (focal and generalized tonic-clonic) | Neuropsychiatric symptoms: Irritability, depression, hostility, psychosis; excellent first-line due to no CYP interactions |
| Sodium Valproate | ↑ Na+ channel inactivation; ↑ GABA synthesis / ↓ degradation | Broad-spectrum (myoclonic, absence, tonic-clonic), bipolar mania, migraine prophylaxis | Fatal hepatotoxicity (monitor LFTs), pancreatitis, alopecia, weight gain, teratogenicity (neural tube defects) |
| Lamotrigine | Blocks voltage-gated Na+ channels; inhibits glutamate release | Broad-spectrum, bipolar depression | Stevens-Johnson syndrome (SJS) and TEN; requires slow upward titration; valproate doubles lamotrigine levels |
| Ethosuximide | Blocks thalamic T-type Ca2+ channels | First-line for Absence seizures (3 Hz spike-and-wave) | EFGHIJ: Ethosuximide causes Fatigue, GI distress, Headache, Itching, Stevens-Johnson syndrome |
| Carbamazepine | Blocks voltage-gated Na+ channels; CYP450 inducer (autoinducer) | First-line for Trigeminal neuralgia and focal seizures | Agranulocytosis, aplastic anemia, SIADH (hyponatremia), SJS/TEN in HLA-B*1502 |
| Phenytoin / Fosphenytoin | Blocks voltage-gated Na+ channels (zero-order kinetics at therapeutic levels) | Focal seizures, status epilepticus maintenance | Gingival hyperplasia, hirsutism, peripheral neuropathy, megaloblastic anemia (folate deficiency), fetal hydantoin syndrome |
General & Local Anesthetics Algorithm
Local anesthetics block voltage-gated Na+ channels from the inside of the cell membrane. Non-ionized uncharged form penetrates lipid membrane, while ionized charged form blocks pore:
| Agent / Class | Key Mechanism & Characteristics | Clinical Application | Toxicities & Reversal |
|---|---|---|---|
| Lidocaine / Bupivacaine (Amides) | Hepatic metabolism; two 'i's in generic name; co-administered with Epinephrine to prolong duration and limit systemic uptake | Infiltration anesthesia, epidural, spinal block | Bupivacaine is highly cardiotoxic (severe refractory ventricular arrhythmias); LAST antidote: 20% IV Lipid Emulsion |
| Succinylcholine | Depolarizing neuromuscular blocker (nicotinic AChR agonist); Phase I (depolarizing fasiculations) → Phase II (desensitization) | Rapid sequence intubation (RSI) | Hyperkalemia (contraindicated in burns, crush injury, denervation), Malignant Hyperthermia (treat with Dantrolene) |
| Rocuronium / Vecuronium | Non-depolarizing competitive nicotinic ACh receptor antagonist | Surgical muscle relaxation, prolonged mechanical ventilation | Reversed by Neostigmine + Glycopyrrolate or Sugammadex (direct cyclodextrin encapsulator) |
| Propofol / Etomidate | GABA-A receptor potentiators; Propofol causes rapid induction and antiemesis; Etomidate is hemodynamically neutral | General anesthesia induction and sedation | Propofol: Hypotension, Propofol Infusion Syndrome (PRIS); Etomidate: Adrenal insufficiency (inhibits 11-beta-hydroxylase) |
Board Traps & Common Distractors
- Succinylcholine is absolutely contraindicated in patients with extensive burn injury (> 24 hours old), crush injury, or spinal cord transection due to widespread upregulation of extrajunctional nicotinic receptors causing catastrophic hyperkalemic cardiac arrest.
- Local Anesthetic Systemic Toxicity (LAST) presents with metallic taste, tinnitus, perioral numbness, visual changes, followed by grand mal seizures and cardiovascular collapse; stop injection immediately and infuse 20% Intralipid.
- Valproate co-administered with Lamotrigine inhibits lamotrigine glucuronidation, doubling serum concentrations and dramatically escalating the risk of fatal Stevens-Johnson Syndrome.