Pharmacology and Pharmacokinetics for Anesthesia
What to master
Build every drug answer around four axes: mechanism, onset/offset (context-sensitive half-time), metabolism/elimination, and side effects. Know the pharmacokinetic model terms - volume of distribution, clearance, half-life, context-sensitive half-time, and the effect-site concentration concept. Propofol: rapid redistribution, hepatic and extrahepatic clearance, hypotension and pain on injection. Thiopentone: zero-order kinetics at high dose, porphyria caution. Ketamine: NMDA antagonism, sympathomimetic, preserves airway tone, emergence phenomena. Etomidate: cardiovascular stability but adrenal suppression. Succinylcholine: depolarising, phase I block, hyperkalaemia in burns/denervation, malignant hyperthermia trigger, pseudocholinesterase deficiency prolongs block. Non-depolarisers: aminosteroids (rocuronium, vecuronium) vs benzylisoquinoliniums (atracurium - Hofmann elimination, laudanosine; cisatracurium - organ-independent). Opioids: receptor effects and the ceiling effect of buprenorphine.
Traps
- Confusing context-sensitive half-time (increases with infusion duration for lipophilic drugs) with elimination half-life.
- Forgetting that atracurium degrades by Hofmann elimination and ester hydrolysis, so it is useful in organ failure.
- Missing the hyperkalaemic risk of succinylcholine in burns after ~24–48 hours and in denervation.
- Assuming neostigmine reverses deep blockade - it requires some spontaneous recovery.
Rule of thumb
For reversal, use sugammadex for rocuronium/vecuronium (encapsulation, dose by depth), neostigmine for others (needs ≥2 twitches on TOF). Match the drug's elimination route to the organ failure in the stem.
Worked example
A patient in renal failure needs paralysis: cisatracurium is the safe choice because its Hofmann degradation is organ-independent, unlike rocuronium which is renally cleared.