Anesthetic Pharmacology Flashcards

A patient receiving a continuous propofol infusion for deep sedation develops metabolic acidosis, hyperkalemia, lipemia, and cardiac arrhythmias after 48 hours. Which mechanism best explains this life-threatening syndrome?

Answer: Propofol inhibits mitochondrial complex I and II, impairing fatty acid oxidation and uncoupling oxidative phosphorylation

Propofol Infusion Syndrome (PRIS) occurs with high-dose, prolonged propofol infusions (>4 mg/kg/hr for >48 hours). The core mechanism is mitochondrial dysfunction: propofol inhibits complexes I and II of the electron transport chain, blocking beta-oxidation of fatty acids. This produces metabolic acidosis, rhabdomyolysis, lipemic plasma, hyperkalemia, and potentially fatal cardiac dysrhythmias. The soybean oil vehicle can cause hypertriglyceridemia but is not the primary mechanism of PRIS.

During moderate sedation with midazolam and fentanyl, a patient develops rigidity of the chest wall and abdomen shortly after a rapid IV fentanyl bolus, making bag-mask ventilation impossible. What is the MOST appropriate immediate pharmacologic intervention?

Answer: Administer succinylcholine 1–1.5 mg/kg IV to achieve muscle relaxation

Opioid-induced chest wall rigidity ('wooden chest syndrome') is a rare but dangerous complication of rapid high-dose opioid administration, mediated by mu-receptor activation in the striatum causing generalized muscle rigidity. Naloxone will reverse rigidity but also reverses all analgesia and sedation, potentially causing acute pain and hemodynamic instability. Succinylcholine (a depolarizing neuromuscular blocker) is the fastest-acting agent to immediately relax skeletal muscle, restoring the ability to ventilate. Flumazenil only reverses benzodiazepines and has no effect on opioid-induced rigidity.

A patient with confirmed pseudocholinesterase deficiency requires succinylcholine for emergency airway management during a dental procedure gone wrong. If succinylcholine is administered, what is the expected clinical consequence compared to a patient with normal enzyme activity?

Answer: Markedly prolonged neuromuscular blockade lasting 2–8 hours instead of the typical 10–15 minutes

Pseudocholinesterase (plasma cholinesterase/butyrylcholinesterase) is the enzyme responsible for metabolizing succinylcholine in the plasma. In patients with pseudocholinesterase deficiency (genetic dibucaine-resistant variants or acquired), succinylcholine is not broken down and remains at the neuromuscular junction far longer than normal. Instead of 10–15 minutes of paralysis, affected patients can experience 2–8+ hours of apnea requiring mechanical ventilatory support. This is called 'scoline apnea.' Succinylcholine requires no activation; it works directly on nicotinic receptors.

Which local anesthetic has the highest risk of methemoglobinemia and is therefore contraindicated in infants under 6 months of age, patients with G6PD deficiency, and those on concurrent medications such as dapsone or nitrates?

Answer: Benzocaine

Benzocaine is an ester-type local anesthetic with a uniquely high propensity to oxidize hemoglobin's iron from ferrous (Fe²⁺) to ferric (Fe³⁺), forming methemoglobin, which cannot carry oxygen. Methemoglobin levels >20% cause cyanosis, dyspnea, and cardiovascular collapse. This risk is highest in infants (lower methemoglobin reductase activity), patients with G6PD deficiency, and those taking oxidizing agents like dapsone or nitrates. Lidocaine and prilocaine can also cause methemoglobinemia but at far higher doses; articaine and bupivacaine carry minimal risk.

A 65-year-old patient on St. John's Wort (hypericum perforatum) as an herbal antidepressant is scheduled for IV sedation with midazolam. Compared to a patient not taking this supplement, you would expect the sedation to be:

Answer: Significantly reduced or inadequate, requiring higher midazolam doses due to CYP3A4 induction

St. John's Wort is a potent inducer of cytochrome P450 3A4 (CYP3A4), the primary enzyme responsible for metabolizing midazolam (and many other drugs). Chronic use upregulates CYP3A4 activity, dramatically increasing the rate at which midazolam is broken down. Clinical studies show St. John's Wort can reduce midazolam plasma concentrations by up to 50–80%, leading to substantially inadequate sedation. This is a clinically significant herb-drug interaction that should be assessed during pre-sedation screening. Patients should ideally discontinue St. John's Wort at least 2 weeks before elective sedation.

Dexmedetomidine produces sedation and anxiolysis through a mechanism distinct from most sedatives used in dental anesthesia. Which unique property makes it particularly valuable for procedural sedation in patients at risk for respiratory depression?

Answer: It activates alpha-2 adrenergic receptors in the locus coeruleus, producing cooperative, arousable sedation with minimal respiratory drive suppression

Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that works by suppressing noradrenergic activity in the locus coeruleus — the brain's primary arousal center. Unlike benzodiazepines, propofol, or opioids, it produces a unique 'cooperative sedation': patients are sedated and calm but can be easily aroused by verbal or tactile stimuli to protect their airway and breathe spontaneously. It has minimal direct effect on medullary respiratory centers, making hypoxic and hypercapnic ventilatory responses largely intact. This pharmacological profile makes it especially valuable for patients with OSA or obesity hypoventilation syndrome.