Pharmacology for the Advanced Anesthesia Candidate
Core principles
Organize pharmacology around pharmacokinetics and pharmacodynamics. Volume of distribution determines loading dose; clearance determines maintenance rate; context-sensitive half-time describes the time for plasma concentration to fall by half after an infusion stops. Propofol is highly lipophilic, causes dose-dependent hypotension, and has antiemetic properties. Etomidate preserves hemodynamics but transiently suppresses cortisol synthesis. Ketamine preserves respiratory drive and blood pressure but can cause emergence delirium and increases secretions. Dexmedetomidine provides sedation without respiratory depression but causes bradycardia and hypertension from peripheral vasoconstriction. Neuromuscular blockers divide into depolarizing and nondepolarizing agents; succinylcholine is metabolized by plasma cholinesterase, and prolonged blockade occurs with enzyme deficiency, including atypical genotypes. Sugammadex encapsulates rocuronium and vecuronium; dosing depends on depth of blockade. Volatile agents are compared by MAC, which is inversely related to potency and is additive among agents.
Local anesthetics
Local anesthetics are weak bases; inflamed, acidic tissue reduces the unionized fraction and slows onset. Toxicity begins with perioral numbness, tinnitus, and agitation, then seizures, coma, and cardiovascular collapse. Bupivacaine is especially cardiotoxic. Treat LAST with airway support, benzodiazepines for seizures, and intravenous lipid emulsion for cardiovascular instability.
Worked example: For a 70-kg patient, plain lidocaine maximum is 4.5 mg/kg = 315 mg; with epinephrine, 7 mg/kg = 490 mg. A 2% solution contains 20 mg/mL, so plain lidocaine allows about 15.7 mL. Rule of thumb: percent concentration × 10 = mg/mL; calculate the maximum volume before drawing up.
Trap: MAC is not a measure of speed of induction, and adding nitrous oxide reduces the MAC of the volatile agent, so potency questions require additive fractions.