Dextromethorphan

Question 1

What is the primary mechanism of action of dextromethorphan?

Answer 1

Dextromethorphan acts as a sigma (σ) receptor agonist in the medulla, suppressing the cough reflex. Dextromethorphan is a sigma receptor agonist that suppresses cough with minimal opioid activity at normal doses. However, it inhibits serotonin reuptake and can cause serotonin syndrome if combined with serotonergic drugs. At high doses, it blocks NMDA receptors, leading to hallucinations and dissociation.

Question 2

How does dextromethorphan differ from opioid cough suppressants like codeine?

Answer 2

Dextromethorphan has trivial mu (μ) and delta (δ) opioid receptor activity, meaning it lacks significant opioid effects such as constipation, respiratory depression, and sedation at therapeutic doses.

Question 3

What are the key pharmacologic effects of dextromethorphan at therapeutic doses?

Answer 3

1. Cough suppression via sigma (σ) receptor activation
2. Minimal opioid-like effects (no significant analgesia, respiratory depression, or sedation)
3. Low abuse potential compared to opioids

Question 4

How does dextromethorphan contribute to serotonin syndrome?

Answer 4

Dextromethorphan inhibits serotonin reuptake and stimulates serotonin receptors, increasing serotonergic activity. When combined with SSRIs, SNRIs, MAOIs, or triptans, it can precipitate serotonin syndrome.

Question 5

What are the signs of serotonin syndrome caused by dextromethorphan?

Answer 5

1. Neuromuscular hyperactivity (clonus, hyperreflexia, muscle rigidity)
2. Autonomic instability (hyperthermia, tachycardia, hypertension)
3. Altered mental status (agitation, hallucinations, confusion)

Question 6

What effects does dextromethorphan have at high doses or overdose?

Answer 6

1. NMDA receptor inhibition, leading to hallucinations, dissociation, and psychosis
2. Respiratory depression and coma at extremely high doses
3. Serotonin syndrome if combined with serotonergic drugs

Question 7

Which common over-the-counter (OTC) medications contain dextromethorphan?

Answer 7

Cough suppressants and multi-symptom cold medications (e.g., Robitussin DM, NyQuil, Delsym).

Question 8

Can dextromethorphan cause addiction?

Answer 8

While dextromethorphan has low addiction potential, recreational abuse is more common in adolescents and young adults due to its dissociative and hallucinogenic effects at high doses.

Question 9

How is dextromethorphan overdose treated?

Answer 9

1. Supportive care (IV fluids, benzodiazepines for agitation)
2. Naloxone if significant respiratory depression occurs (rare but possible at very high doses)
3. Cyproheptadine if serotonin syndrome develops

Question 10

What combination medications with dextromethorphan may increase overdose risk?

Answer 10

Acetaminophen-containing cold medications, which can cause liver toxicity in overdose (e.g., multi-symptom cold remedies).

Question 11

Does dextromethorphan withdrawal cause rebound cough?

Answer 11

No, cough does not recur upon withdrawal, unlike decongestants (e.g., oxymetazoline) that cause rebound congestion with prolonged use.