Nasal Anticholinergics
Ipratropium bromide is the primary nasal anticholinergic available for treating rhinorrhea, marketed as Atrovent nasal spray in two concentrations (0.03% and 0.06%). 1, 2, 3
Available Formulations
- Ipratropium bromide nasal spray 0.03% is approved for rhinorrhea associated with perennial allergic and nonallergic rhinitis in patients 6 years and older 1, 2
- Ipratropium bromide nasal spray 0.06% is approved for rhinorrhea associated with the common cold in patients 5 years and older 1, 2, 3
- Glycopyrrolate is mentioned as another quaternary ammonium muscarinic receptor antagonist, though ipratropium bromide has been the most extensively studied intranasal anticholinergic agent 1
Mechanism and Pharmacology
- Ipratropium bromide is a quaternary ammonium compound that blocks muscarinic receptors locally on the nasal mucosa, inhibiting cholinergically mediated glandular secretions 1, 2
- The quaternary structure prevents systemic absorption across biological membranes, minimizing systemic anticholinergic effects (neurologic, ophthalmic, cardiovascular, gastrointestinal) that occur with tertiary anticholinergic amines 1, 2
- It blocks both histamine-induced and antigen-induced nasal secretions, which are significantly mediated through cholinergic pathways 1, 2
Dosing Regimens
- For perennial rhinitis (0.03% concentration): 42 μg per nostril (2 sprays) three times daily 2, 4
- For common cold (0.06% concentration): 84 μg per nostril (2 sprays) three times daily 2
- Duration of action is 4-12 hours with 40 μg dose and up to 18 hours with 80 μg dose, suggesting that less frequent dosing than four times daily may be adequate for many patients 5
Clinical Efficacy Spectrum
- Specifically effective for rhinorrhea only—ipratropium does not relieve nasal congestion or sneezing 1, 3
- Effective in cold-induced rhinorrhea (e.g., skiers), gustatory rhinitis (eating-induced), and post-viral rhinorrhea 1, 2
- Onset of action occurs rapidly, with benefit evident by the first or second day of treatment 4, 6
Combination Therapy Advantages
- Ipratropium plus intranasal corticosteroids is more effective than either agent alone for rhinorrhea without increased adverse events 1, 2, 4
- Ipratropium plus antihistamines (such as terfenadine) provides superior control of rhinorrhea compared to antihistamine alone, with 69% of patients responding better to combination therapy 1, 6
- Ipratropium has faster onset during the first week compared to beclomethasone, while beclomethasone is superior for congestion and sneezing 4
Safety Profile
- Epistaxis occurs in 9% of patients versus 5% with placebo 1, 2, 7
- Nasal dryness affects 5% of patients versus 1% with placebo 1, 2, 7
- Blood-tinged mucus may occur but is mild and self-limiting 7
- Does not alter physiologic nasal functions including sense of smell, ciliary beat frequency, mucociliary clearance, or nasal air conditioning capacity 1, 2, 7
Critical Clinical Pitfalls
- Do not use as monotherapy when nasal congestion is the primary complaint—ipratropium has no decongestant effect and requires addition of intranasal corticosteroids or oral decongestants 2
- Not effective for sneezing—antihistamines are more appropriate for this symptom 2
- FDA approval limits use to 4 days for common cold and 3 weeks for seasonal allergic rhinitis, though safety beyond these durations has not been established 3
- In pediatric patients with perennial allergic rhinitis, twice-daily dosing may be inadequate; three-times-daily administration provides better control 8