Pharmacology Flashcards

A patient receiving IV midazolam for deep sedation begins showing paradoxical excitation, agitation, and combativeness. Which pharmacological mechanism best explains this reaction?

Answer: Disinhibition of subcortical structures from suppression of inhibitory interneurons in the limbic system

Paradoxical reactions to benzodiazepines are thought to occur through disinhibition — the drug suppresses GABAergic inhibitory interneurons in the limbic system, releasing subcortical excitatory activity rather than producing sedation. This is more common in children, elderly patients, and those with underlying psychiatric conditions. It is NOT due to receptor antagonism or metabolite accumulation.

You administer dexmedetomidine as an adjunct for office-based deep sedation. Compared to propofol, which hemodynamic pattern is most characteristic of dexmedetomidine at the onset of a bolus dose?

Answer: Transient hypertension followed by bradycardia and hypotension

A bolus of dexmedetomidine can cause a transient hypertensive response due to peripheral alpha-2B receptor activation causing vasoconstriction, followed by centrally-mediated sympatholysis resulting in bradycardia and hypotension. This biphasic hemodynamic pattern is a distinguishing pharmacodynamic feature and a key reason boluses are given slowly or avoided.

A 68-year-old patient on chronic phenytoin therapy requires IV sedation with fentanyl and midazolam. Which pharmacokinetic alteration is most clinically relevant when dosing these agents?

Answer: Phenytoin induces CYP3A4, reducing the efficacy of both fentanyl and midazolam

Phenytoin is a potent inducer of CYP3A4 (and other CYP enzymes). Both fentanyl and midazolam are primarily metabolized by CYP3A4. Chronic phenytoin use increases their hepatic clearance, reducing plasma concentrations and clinical effect — patients may require higher doses to achieve adequate sedation. This is a classic pharmacokinetic drug interaction.

During a dental procedure under IV sedation, a patient develops acute laryngospasm that does not resolve with positive pressure ventilation. The smallest dose of succinylcholine that would be used to break laryngospasm ("intubating dose") in a 70 kg adult is approximately:

Answer: 0.1–0.2 mg/kg (7–14 mg)

For laryngospasm not responsive to positive pressure ventilation, a subparalyzing 'laryngospasm notch' dose of succinylcholine (0.1–0.2 mg/kg IV) is used to relax the laryngeal muscles without producing full neuromuscular blockade. Full intubating doses (1–1.5 mg/kg) are reserved for RSI intubation. Using a subparalyzing dose allows the patient to continue spontaneous respiration after laryngospasm is broken.

A patient with known G6PD deficiency is scheduled for IV deep sedation. Which agent poses the greatest risk of triggering hemolytic anemia in this patient?

Answer: Prilocaine

Prilocaine is metabolized to ortho-toluidine, which can oxidize hemoglobin to methemoglobin. In patients with G6PD deficiency, the inability to regenerate NADPH impairs reduction of methemoglobin back to hemoglobin, and oxidative stress from prilocaine metabolites can trigger hemolytic anemia. Propofol, ketamine, and fentanyl do not carry this risk in G6PD-deficient patients.

When comparing the context-sensitive half-time of remifentanil versus fentanyl after a 3-hour continuous infusion, which statement is most accurate?

Answer: Remifentanil maintains a context-sensitive half-time of approximately 3–4 minutes regardless of infusion duration

Remifentanil is unique among opioids because it is metabolized by nonspecific plasma and tissue esterases, making its elimination independent of infusion duration. Its context-sensitive half-time remains approximately 3–4 minutes regardless of how long the infusion runs. In contrast, fentanyl undergoes significant redistribution and hepatic metabolism; its context-sensitive half-time rises markedly with longer infusions (exceeding 200+ minutes after a 3-hour infusion) due to accumulation in peripheral tissues.