Drug Interactions and Contraindications in Anesthesia Flashcards

A patient who takes phenelzine for treatment-resistant depression is scheduled for IV moderate sedation. Which opioid is absolutely contraindicated because of the risk of a potentially fatal interaction?

Answer: Meperidine

Phenelzine is a monoamine oxidase inhibitor (MAOI). Meperidine blocks serotonin reuptake, so combining it with an MAOI can cause serotonin syndrome: hyperthermia, agitation, muscle rigidity, seizures, cardiovascular instability and death. Fentanyl still needs caution with serotonergic drugs, but meperidine is the classic absolute contraindication with MAOIs. Morphine and hydromorphone do not carry this serotonergic risk.

A patient taking propranolol receives several cartridges of lidocaine 2% with 1:100,000 epinephrine. A few minutes later the patient's blood pressure rises sharply and the heart rate drops. What is the mechanism?

Answer: Beta-2 vasodilation is blocked, leaving alpha-1 vasoconstriction unopposed, followed by a reflex vagal slowing of the heart

Propranolol is a nonselective beta blocker. In skeletal muscle vascular beds, epinephrine's beta-2 effect normally causes vasodilation that partly offsets its alpha-1 vasoconstriction. When beta-2 is blocked, alpha-1 vasoconstriction goes unopposed and blood pressure rises sharply. The baroreceptor reflex then slows the heart, and beta-1 blockade means nothing counteracts the slowing. Cardioselective beta-1 blockers such as metoprolol carry much less of this risk.

A patient started clarithromycin 3 days ago for a respiratory infection and is scheduled for oral midazolam sedation today. What is the most appropriate expectation?

Answer: Midazolam's effect will be stronger and longer because clarithromycin inhibits CYP3A4

Midazolam is metabolized mainly by hepatic and intestinal CYP3A4. Clarithromycin (like erythromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice) strongly inhibits CYP3A4. This can raise midazolam levels several-fold and cause deep, prolonged sedation and respiratory depression, especially with oral dosing because first-pass metabolism is reduced. The dose should be reduced or the procedure postponed. Enzyme inducers such as rifampin, carbamazepine and St. John's wort have the opposite effect.

A patient with known G6PD deficiency who also takes dapsone needs a mandibular block. Which local anesthetic carries the greatest risk of a serious reaction in this patient and should be avoided?

Answer: Prilocaine 4% plain

Prilocaine is metabolized to o-toluidine, which oxidizes hemoglobin to methemoglobin. G6PD deficiency limits the red cell's ability to reverse this oxidation, and dapsone is itself an oxidizing drug. Together these sharply raise the risk of clinically significant methemoglobinemia: cyanosis that does not improve with oxygen and 'chocolate-brown' blood. Methylene blue, the usual antidote, may not work and can cause hemolysis in G6PD deficiency. Articaine and topical benzocaine also carry methemoglobinemia risk.

A patient over-sedated with midazolam has slow, shallow breathing. The chart shows the patient takes clonazepam daily for a seizure disorder. What is the main concern with giving flumazenil?

Answer: Flumazenil may trigger acute benzodiazepine withdrawal and seizures

Flumazenil competitively reverses benzodiazepines at the GABA-A receptor. In a patient who depends on a benzodiazepine for long-term seizure control, rapid reversal can cause acute withdrawal and lower the seizure threshold, triggering seizures that may be hard to control. Seizure risk is also high after mixed overdoses involving tricyclic antidepressants. In these patients, airway support and ventilation are first-line, and any flumazenil should be given in small, slowly titrated doses, if at all.

A patient taking amitriptyline is having restorative work. Compared with epinephrine, why is levonordefrin (in mepivacaine 2% with 1:20,000 levonordefrin) generally avoided in this patient?

Answer: Tricyclics block norepinephrine reuptake, and levonordefrin's mostly alpha-adrenergic effects are amplified more than epinephrine's, causing a larger rise in blood pressure

Tricyclic antidepressants block neuronal reuptake of catecholamines, which strengthens the effects of injected vasoconstrictors. Levonordefrin acts mostly on alpha receptors and has little beta-2 vasodilating effect to offset vasoconstriction. Studies show its pressor effect is amplified more than epinephrine's, causing a significant rise in blood pressure. Recommended practice is to avoid levonordefrin and limit epinephrine (often to about 0.04 mg) while monitoring vital signs.