A 39-year-old woman comes to the office due to a nagging cough. Two weeks ago, the patient had a mild upper respiratory illness which resolved spontaneously after several days. Since then, she has had cough that is productive of minimal clear sputum. The patient has had no shortness of breath or chest pain. She took unexpired, leftover dextromethorphan for 2 days. The patient's only other medical condition is major depression, for which she takes sertraline. She does not use tobacco, alcohol, or illicit drugs. Vital signs and physical examination show no abnormalities. Use of dextromethorphan is most concerning for which of the following in this patient?

Question

A 39-year-old woman comes to the office due to a nagging cough.  Two weeks ago, the patient had a mild upper respiratory illness which resolved spontaneously after several days.  Since then, she has had cough that is productive of minimal clear sputum.  The patient has had no shortness of breath or chest pain.  She took unexpired, leftover dextromethorphan for 2 days.  The patient's only other medical condition is major depression, for which she takes sertraline.  She does not use tobacco, alcohol, or illicit drugs.  Vital signs and physical examination show no abnormalities.  Use of dextromethorphan is most concerning for which of the following in this patient?

Quizplus · Accepted Answer

11ec160b_3c5e_591e_9249_9fa6d841e8d3_MD0001_00 Dextromethorphan (DXM) is a popular cough suppressant (antitussive agent) that is readily available over the counter. Its primary mechanism of action is inhibition of the medullary cough center through sigma (σ) receptor activation. Although structurally very closely related to other opioid morphinans (eg, codeine, morphine), DXM has trivial mu (μ) and delta (δ) opioid receptor affinity. Therefore, classic opioid adverse effects (eg, constipation, respiratory depression, analgesia, sedation) are not seen at therapeutic doses. This favorable pharmacologic profile makes DXM a first-choice agent for cough suppression. However, DXM also increases serotonin activity in the CNS by decreasing the rate of presynaptic serotonin reuptake and directly stimulating serotonin receptors. For this reason, DXM abuse can cause serotonin syndrome, manifesting as muscular hypertonia, spasticity (eg, clonus, hyperreflexia), autonomic instability (eg, hyperthermia, hypertension), and encephalopathy. This potentially fatal condition most often occurs in settings of overdose or accidental drug interaction with other serotonergic drugs (eg, selective serotonin reuptake inhibitors, triptans, monoamine oxidase inhibitors). (Choice A) Although DXM has the potential for abuse, addiction is less likely than with opioid cough suppressants (eg, codeine). Recreational drug use typically begins in peer settings, and adolescents and young adults are at greatest risk; this 39-year-old woman has no history of recreational drug use and is likely at low risk. (Choice C) DXM has no intrinsic hepatotoxicity. However, acute liver injury can occur in overdose scenarios involving combination dextromethorphan-acetaminophen preparations (eg, multi-symptom cold remedies). (Choice D) Although it has negligible μ receptor agonism at therapeutic doses, DXM at high doses may cause intoxication that can occasionally elicit enough μ receptor agonism to produce hypoventilation and stupor. These symptoms can be reversed with naloxone. (Choice E) Patients who use over-the-counter decongestants (eg, oxymetazoline or phenylephrine sprays, oral pseudoephedrine) for prolonged periods can develop rhinitis medicamentosa, characterized by rebound nasal congestion, rhinorrhea, and turbinate hypertrophy. However, rebound cough is not observed on DXM withdrawal. Educational objective: Dextromethorphan (DXM) is a popular over-the-counter antitussive agent that acts on sigma receptors to suppress the medullary cough center. DXM also has an off-target action on serotonin transports and receptors in the CNS. Overdose or accidental interaction with other serotonergic medications (eg, selective serotonin reuptake inhibitors, antidepressants) can precipitate serotonin syndrome.

A 39-Year-Old Woman Comes to the Office Due to a Nagging