Today’s USMLE® Step 1 question of the day features a 27-year-old woman with a runny nose, cough, and sore throat who’s also feeling anxious. What medication mechanism of action is at work? Let’s find out!
A 27-year-old woman presents to her outpatient provider for evaluation of nasal congestion and clear nasal discharge. These symptoms began two days ago and have been bothersome, as she frequently feels the urge to blow her nose. The patient has also experienced a cough and sore throat. Past medical history is unremarkable. Temperature is 38.3°C (100.9°F), blood pressure is 112/70 mmHg, and pulse is 69/min. Mild erythema is present in the oropharynx. The lungs are clear to auscultation bilaterally. The patient is prescribed a nasal decongestant and is provided with anticipatory guidance on its side effects, which can include hypertension, anxiety, and rebound congestion with prolonged use.
Which of the following best describes this medication’s mechanism of action?
A. Blockade of NMDA receptors
B. Antagonization of H1 receptors
C. Inactivation of NF-KB
D. Stimulation of α₁-adrenergic receptors
E. Blockade of leukotriene receptors
Scroll down for the correct answer!
The correct answer to today’s USMLE® Step 1 Question is…
D. Stimulation of α₁-adrenergic receptors
Correct: See Main Explanation.
Incorrect Answer Explanations
A. Blockade of NMDA receptors
Incorrect: Dextromethorphan is an antitussive that has activity, in part, through NMDA-receptor antagonism. Side effects, particularly with overdose, include hallucinations, confusion, euphoria, nausea, vomiting, and nystagmus. In severe cases, patients may experience seizures, coma, and respiratory depression.
B. Antagonization of H1 receptors
Incorrect: Antihistamines (e.g., diphenhydramine, loratadine, and cetirizine) can be used to treat nasal symptoms caused by allergies and may modestly improve rhinorrhea associated with the common cold. First-generation antihistamines can cause drowsiness, anticholinergic symptoms (e.g., urinary retention, mydriasis, and dry mouth), and α₁-adrenergic antagonism can cause postural hypotension.
C. Inactivation of NF-KB
Incorrect: Corticosteroids inhibit NF-KB and block the production of downstream inflammatory cytokines. Intranasal corticosteroids can be used to treat nasal congestion caused by allergies. However, these medications are not typically used to treat cold symptoms and would not account for the constellation of side effects described in the question stem.
E. Blockade of leukotriene receptors
Incorrect: Medications such as montelukast and zafirlukast block leukotriene receptors and are primarily used in the treatment of asthma. Side effects may include hypersensitivity reactions, headaches, gastrointestinal irritation, and, particularly with montelukast, neuropsychiatric effects.
Main Explanation
This patient presents with symptoms of an uncomplicated viral upper respiratory infection, or common cold. The side effect profile of hypertension, anxiety, and rebound congestion is consistent with an alpha-adrenergic decongestant, such as oxymetazoline and pseudoephedrine. These drugs produce adrenergic stimulation, particularly of α₁ receptors, causing vasoconstriction of blood vessels in the nasal mucosa. This reduces mucosal edema and improves nasal airflow.
Topical agents administered as nasal sprays, such as oxymetazoline, should generally not be used for more than a few days because prolonged use can cause rebound congestion. Systemic agents taken orally, such as pseudoephedrine, can produce hypertension and central nervous system stimulation, causing restlessness or anxiety.
Major Takeaway
Alpha-adrenergic decongestants reduce nasal congestion by stimulating α₁ receptors, causing vasoconstriction and decreased nasal mucosal edema. Topical agents can cause rebound congestion with prolonged use, whereas oral agents can cause hypertension, restlessness, and anxiety.
Want to learn more about this topic?
Watch this Osmosis video: Adrenergic receptors
References
- Johnson, D.A., Hricik, J.G. (1993) The pharmacology of alpha-adrenergic decongestants. Pharmacotherapy. 13(6 Pt 2), 110S-115S. PMID: 7507588.
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