Anesthetic Pharmacology Flashcards

A patient receiving a continuous propofol infusion for sedation over 48 hours develops metabolic acidosis, hyperkalemia, rhabdomyolysis, and cardiac arrhythmias. Which mechanism best explains this constellation of findings?

Answer: Propofol inhibits mitochondrial electron transport chain complexes II and IV, impairing fatty acid oxidation and causing cytotoxic accumulation of acylcarnitine metabolites

This describes Propofol Infusion Syndrome (PRIS), a rare but potentially fatal complication. Propofol impairs mitochondrial respiratory chain function — specifically complexes II and IV — disrupting fatty acid oxidation. This leads to accumulation of toxic acylcarnitine and malonylcarnitine intermediates, causing metabolic acidosis, rhabdomyolysis, cardiac dysfunction (particularly right bundle branch block or ST-segment changes), and renal failure. Risk is highest with infusions >4 mg/kg/hr for >48 hours.

When administered to a patient with a dibucaine number of 20, succinylcholine 1 mg/kg would be expected to produce neuromuscular blockade lasting approximately how long?

Answer: 4–8 hours (markedly prolonged)

The dibucaine number reflects the percentage inhibition of plasma cholinesterase (pseudocholinesterase) by dibucaine. A normal dibucaine number is 70–85, indicating normal enzyme. A dibucaine number of 20 indicates homozygous atypical pseudocholinesterase — the most severely affected genotype. These patients cannot hydrolyze succinylcholine normally, resulting in paralysis lasting 4–8 hours instead of the usual 10–15 minutes. A dibucaine number of 40–60 indicates heterozygous atypical enzyme, causing moderate prolongation to 20–30 minutes.

A 45-year-old patient is given dexmedetomidine for procedural sedation. Fifteen minutes into the infusion, you observe bradycardia and paradoxical hypertension followed by hypotension. Which pharmacodynamic mechanism best explains the initial hypertensive phase?

Answer: Peripheral alpha-2B receptor activation on vascular smooth muscle causes transient vasoconstriction before central sympatholysis predominates

Dexmedetomidine is a highly selective alpha-2 agonist (alpha-2:alpha-1 ratio of 1620:1). While its predominant sedative and hypotensive effects are mediated by central (locus coeruleus) alpha-2A receptors reducing sympathetic outflow, peripheral vascular smooth muscle contains alpha-2B receptors that, when stimulated during the bolus/loading phase, produce direct vasoconstriction. This peripheral effect is transient and precedes central sympatholysis, creating a biphasic hemodynamic response: initial hypertension/bradycardia, then hypotension/bradycardia.

Which of the following correctly describes the pharmacokinetic consequence of context-sensitive half-time and why remifentanil is uniquely advantageous in prolonged infusions compared to fentanyl?

Answer: Remifentanil has a context-sensitive half-time that remains approximately 3–4 minutes regardless of infusion duration because it undergoes ester hydrolysis by nonspecific plasma and tissue esterases, independent of hepatic or renal clearance

Context-sensitive half-time is the time required for plasma concentration to decrease by 50% after stopping an infusion of a given duration (the 'context' is infusion duration). For fentanyl, this increases dramatically — from ~1 hour after a 1-hour infusion to >9 hours after an 8-hour infusion — due to redistribution from peripheral compartments. Remifentanil is metabolized by nonspecific esterases ubiquitous in blood and tissues (not dependent on pseudocholinesterase, hepatic function, or renal function), yielding a stable context-sensitive half-time of ~3–4 minutes regardless of infusion duration. This makes its offset completely predictable.

A dental patient on phenelzine (an irreversible MAO inhibitor) requires local anesthesia. Which of the following anesthetic-related drug interactions poses the MOST immediately life-threatening risk?

Answer: Meperidine administered for pain management causing serotonin syndrome with hyperthermia, rigidity, and cardiovascular collapse

While epinephrine with MAOIs is a real concern (indirectly-acting sympathomimetics like ephedrine are dangerous; directly-acting agents like epi carry moderate risk), the meperidine-MAOI interaction is considered the most immediately life-threatening combination in anesthesia. MAO-A metabolizes serotonin; when inhibited, meperidine's serotonin reuptake inhibition and possible serotonin release cause catastrophic serotonin syndrome: hyperthermia, neuromuscular hyperactivity (clonus, rigidity, tremor), and cardiovascular instability that can be rapidly fatal. This interaction is absolutely contraindicated. Epinephrine at dental doses typically used is a lower acute risk by comparison.

During office-based deep sedation with ketamine, a patient develops laryngospasm. The provider administers succinylcholine 0.1 mg/kg IV to break the spasm but it proves ineffective. What is the most pharmacologically sound explanation?

Answer: The dose of 0.1 mg/kg is subtherapeutic for inducing sufficient depolarization at the laryngeal muscles; a dose of 1–1.5 mg/kg is required to reliably break laryngospasm

Breaking laryngospasm with succinylcholine requires a full intubating-level dose (1–1.5 mg/kg IV, or 4 mg/kg IM if no IV access). At 0.1 mg/kg — a so-called 'mini-dose' — there is insufficient depolarization to overcome the sustained glottic closure of laryngospasm. The concept of a 'sub-paralytic' dose for laryngospasm is a common clinical myth; studies have shown it may paradoxically worsen muscle fasciculation without achieving the sustained depolarization needed. The correct treatment of complete laryngospasm unresponsive to positive pressure is succinylcholine 1–1.5 mg/kg IV (or 4 mg/kg IM), with atropine given to children to prevent bradycardia.