Inhaled anesthetic potency is inversely related to the minimum alveolar concentration (MAC), while speed of onset is governed by the blood:gas partition coefficient, with lower values yielding faster onset and nitrous oxide being the prototypical fast agent. Methoxyflurane is rarely used because of fluoride-induced nephrotoxicity. Propofol potentiates GABA-A receptors for rapid induction and emergence but can cause propofol infusion syndrome (acidosis, rhabdomyolysis, cardiac failure) with prolonged high-dose use, plus hypotension on induction. Etomidate is hemodynamically stable but suppresses the adrenal axis via 11β-hydroxylase inhibition, which is associated with increased mortality in sepsis. Ketamine is an NMDA antagonist producing dissociative anesthesia with bronchodilation, sympathomimetic effects (increased blood pressure and heart rate), and minimal respiratory depression, useful in pediatrics and trauma, though emergence reactions and hallucinations can occur.
Local anesthetics block voltage-gated sodium channels on nerve axons. Amides (lidocaine, bupivacaine) are metabolized in the liver, while esters (procaine, tetracaine) are metabolized by plasma cholinesterase and can cross-react with PABA allergy. Lidocaine also serves as a Class IB antiarrhythmic, with CNS toxicity (perioral numbness, tinnitus, seizures, coma) at high plasma levels and cardiac depression at very high levels. Bupivacaine is more cardiotoxic than lidocaine if delivered intravascularly, producing difficult-to-treat ventricular arrhythmias. Epinephrine is added to local anesthetics for vasoconstriction, which prolongs anesthesia, reduces systemic absorption, and decreases bleeding, but is avoided in end-arterial sites (fingers, toes, nose, penis) due to ischemia risk.
Opioids act on mu-opioid receptors and share key adverse effects: respiratory depression, miosis, constipation, tolerance, and dependence. Morphine additionally releases histamine, which can cause hypotension and bronchospasm. Naloxone is a competitive antagonist for acute overdose reversal, but its short half-life means re-dosing may be needed, particularly with methadone. Naltrexone is a long-acting antagonist for alcohol use disorder and opioid dependence maintenance. Methadone is a long-acting mu agonist and NMDA antagonist with a long, variable half-life that can lead to accumulation, used for opioid maintenance and chronic pain and notable for QT prolongation. Buprenorphine is a partial mu agonist and kappa antagonist with a ceiling effect on respiratory depression; the sublingual combination with naloxone (Suboxone) deters intravenous misuse. Tramadol is a weak mu agonist plus serotonin and norepinephrine reuptake inhibitor that lowers the seizure threshold and can cause serotonin syndrome when combined with SSRIs or MAOIs. Fentanyl is approximately 100 times more potent than morphine, with rapid onset and short duration by intravenous routes but available transdermally for chronic pain. Diphenoxylate combined with atropine (Lomotil) is used for diarrhea, with the atropine component producing anticholinergic effects at supratherapeutic doses to discourage abuse.