Ipratropium

Inhaled anticholinergic bronchodilator used most often in combination with a short-acting β₂-agonist (e.g., albuterol) for acute COPD exacerbations and moderate-to-severe asthma in the ED/ICU and prehospital setting.

Mechanism: Nonselective muscarinic receptor antagonist that blocks M₃ receptors in bronchial smooth muscle, reducing vagally mediated bronchoconstriction and mucus secretion. Quaternary ammonium structure → minimal CNS penetration and very low systemic absorption when inhaled.

Onset: Bronchodilation begins within ~15 minutes, with peak effect around 1–2 hours and duration ~4–6 hours for inhaled doses. It is slower in onset than albuterol but provides additive/synergistic bronchodilation when used together.

Typical adult ED dosing (nebulized) for acute asthma/COPD: 0.5 mg (500 mcg) nebulized every 20 minutes for 3 doses, often mixed with albuterol ("DuoNeb"), then 0.5 mg every 4–6 hours as needed. Many protocols limit ipratropium to the initial 3 doses in asthma; COPD exacerbations may continue it on a scheduled basis.

Typical pediatric ED dosing (nebulized): 0.25–0.5 mg nebulized every 20 minutes for 3 doses in moderate/severe asthma (often 250 mcg for <20 kg and 500 mcg for ≥20 kg) in combination with albuterol.

MDI dosing: Atrovent HFA (17 mcg/actuation) commonly 2 puffs four times daily, with additional puffs q4–6h PRN in chronic COPD; in the ED, ipratropium is more often delivered via nebulization or as Combivent (ipratropium/albuterol) if the patient can effectively use MDI + spacer.

• Generic Name: Ipratropium bromide
• Brand Names: Atrovent HFA (MDI), Atrovent (nebulizer solution), various combination products with albuterol (e.g., DuoNeb, Combivent), multiple generics – availability is region- and institution-specific

Short-acting muscarinic antagonist (SAMA); inhaled anticholinergic bronchodilator

Mechanism of Action:

• Ipratropium is a nonselective, quaternary ammonium muscarinic receptor antagonist with primary effects on M₃ receptors in bronchial smooth muscle
• By blocking M₁ and M₃ receptors on airway smooth muscle and submucosal glands, ipratropium inhibits acetylcholine-mediated bronchoconstriction and reduces mucus secretion, leading to bronchodilation and decreased airway resistance
• Its quaternary ammonium structure limits systemic absorption and prevents significant penetration of the blood–brain barrier, reducing CNS anticholinergic effects compared with tertiary amines (e.g., atropine)
• Because ipratropium targets cholinergic tone rather than β₂ receptors, it is particularly useful as an adjunct when β₂-agonist responsiveness is reduced (e.g., severe COPD, chronic bronchitis) or when β₂-agonist side effects are problematic

Pharmacokinetics (Inhaled – High-Yield):

• Route: Administered via MDI (Atrovent HFA, 17 mcg per actuation) or nebulized solution (0.02% = 0.25 mg/mL; typical unit dose 0.5 mg in 2.5 mL). Nasal spray formulations exist for rhinorrhea but are not the focus here
• Onset: Bronchodilation typically begins within 15 minutes after inhalation; clinically meaningful improvement in FEV₁ may be seen by 30 minutes
• Peak effect: ~1–2 hours post-inhalation
• Duration: Bronchodilatory effect generally lasts 4–6 hours, which is longer than many SABAs but shorter than long-acting antimuscarinics (LAMAs)
• Systemic absorption: Relatively low after inhalation; swallowed fraction has poor GI absorption. Protein binding is modest (~0–9%)
• Metabolism & elimination: Partially metabolized in the liver to inactive metabolites; majority excreted unchanged in the urine. Terminal half-life is roughly 1.5–2 hours after inhalation, but clinical effect lasts longer due to receptor binding dynamics
• Renal impairment: Systemic accumulation is possible with chronic high-dose use, but standard inhaled ED/ICU dosing is rarely an issue. No specific dose adjustment is typically required for short-term use

Medication Forms & Common Concentrations:

• Nebulizer solution: 0.02% (0.25 mg/mL) in unit-dose vials, commonly 0.5 mg in 2.5 mL for adults; pediatric vials may be 0.25 mg in 2.5 mL
• Combination nebulizer (DuoNeb or equivalent): Ipratropium 0.5 mg + albuterol 2.5 mg in 3 mL for adult dosing
• MDI (Atrovent HFA): 17 mcg per actuation; typically used with a spacer for optimal lung deposition
• MDI combination (Combivent Respimat): Ipratropium 20 mcg + albuterol 100 mcg per actuation
• Nasal spray: Ipratropium 0.03% and 0.06% for rhinorrhea (dosing not detailed here)

Dosing – Inhaled Ipratropium (ED/ICU/Prehospital):

Additional Dosing Notes:

• Always use ipratropium as an adjunct, not a replacement, for short-acting β₂-agonists (SABA) in acute asthma and COPD exacerbations
• Evidence supports using ipratropium in moderate-to-severe asthma exacerbations (e.g., FEV₁/PEF <40–60% predicted) early in the ED course to reduce hospitalization; benefit is less clear in mild exacerbations
• In COPD exacerbations, continued scheduled ipratropium (with SABA) is often beneficial during the acute phase, with a plan to transition to LAMA-based maintenance therapy after stabilization
• Nebulizer delivery is preferred over MDI in severely dyspneic, fatigued, or uncooperative patients; MDI + spacer is acceptable in stable patients who can coordinate inhalation

Contraindications:

• Known hypersensitivity to ipratropium, atropine, or other anticholinergic derivatives
• History of severe allergic reaction (e.g., anaphylaxis) to soya lecithin or related food products with older CFC propellant formulations (less relevant with current HFA inhalers but may persist in some regions)

Major Precautions:

• Narrow-angle glaucoma: Nebulized ipratropium mist can precipitate angle-closure glaucoma if it contacts the eyes; protect the eyes with a well-fitted mask or mouthpiece and wipe excess medication from the face
• Prostatic hypertrophy or bladder outlet obstruction: Anticholinergic effects may worsen urinary retention; monitor especially in older male COPD patients receiving frequent doses
• Cystic fibrosis: Increased risk of paradoxical bronchospasm or thickened secretions has been reported; monitor response closely
• Paradoxical bronchospasm: Rare but possible with any inhaled bronchodilator; if it occurs, discontinue ipratropium and treat per bronchodilator protocol
• Pregnancy and lactation: Generally considered low systemic risk when inhaled; commonly used in pregnant patients with asthma/COPD as clinically indicated

Common (Inhaled):

• Dry mouth and throat irritation
• Cough or mild paradoxical bronchospasm
• Headache or dizziness
• Nausea, gastrointestinal upset
• Blurred vision or eye irritation if nebulizer mist reaches the eyes

Serious (Uncommon):

• Acute narrow-angle glaucoma with eye pain, blurred vision, halos around lights (from ocular exposure)
• Urinary retention, particularly in patients with BPH or bladder outlet obstruction
• Severe hypersensitivity reaction, including rash, bronchospasm, or anaphylaxis
• Significant paradoxical bronchospasm requiring discontinuation and alternative therapy

• Clinical response: Respiratory rate, work of breathing, accessory muscle use, presence of wheeze, and ability to speak in full sentences
• Objective measures when available: FEV₁, peak expiratory flow (PEF), or bedside spirometry before and after treatments in asthma/COPD exacerbations
• Heart rate and blood pressure, particularly when ipratropium is combined with high-dose β₂-agonists
• Eye symptoms and visual changes when nebulized ipratropium is used with poorly fitting masks (watch for signs of angle-closure glaucoma)
• Urinary symptoms in older men or patients with preexisting urinary retention risks receiving frequent ipratropium doses

• Acute exacerbation of COPD (bronchospasm) – as part of initial nebulized bronchodilator therapy, usually in combination with albuterol
• Moderate-to-severe acute asthma exacerbation – especially in the ED/ICU and prehospital setting, combined with albuterol in the first 1–3 hours of treatment to reduce hospitalization and improve lung function
• Chronic maintenance therapy in COPD via MDI (ipratropium alone or in combination with albuterol) when LAMAs are unavailable or contraindicated
• Off-label: Acute bronchospasm triggered by irritants or infections, sometimes used in upper airway disease or post-extubation bronchospasm at clinician discretion
• Nasal formulations: symptomatic relief of rhinorrhea in allergic or nonallergic rhinitis (ENT/primary care setting; not the main ICU/ED use)

• Global Initiative for Chronic Obstructive Lung Disease (GOLD). (2024). Global strategy for the diagnosis, management, and prevention of COPD.
• Global Initiative for Asthma (GINA). (2024). Global strategy for asthma management and prevention.
• DrugBank Online. (2024). Ipratropium (DB00332). DrugBank. https://go.drugbank.com/drugs/DB00332
• National Asthma Education and Prevention Program (NAEPP). (2020). 2020 Focused updates to the asthma management guidelines. Journal of Allergy and Clinical Immunology, 146(6), 1217–1270.
• EMCrit Project. (2024). Acute exacerbation of COPD (IBCC). https://emcrit.org/ibcc/copd/