Ipratropium bromide

Mechanism

Mechanism of action

Ipratropium acts as a non-selective competitive antagonist of muscarinic receptors M₁, M₂ and M₃ in the airway:

• M₃ blockade (Bronchial): Prevents the binding of acetylcholine released by the vagus to the M₃ receptor on the smooth muscle cell. This inhibits the cascade mediated by G_q → PLC → IP₃ → [Ca^{2+]_i, resulting in effective bronchodilation. It also reduces mucous hypersecretion in the submucosal glands.}
• M₁ blockade (Ganglionic): Prevents the facilitation of vagal transmission in the ganglia of the upper airway.
• M₂ blockade (Presynaptic autoreceptor): Blocks the negative feedback control that slows the release of acetylcholine. By inhibiting the M₂ receptor, it can transiently increase the release of acetylcholine at the synaptic level, which partially limits its bronchodilator efficacy compared to long-acting selective anticholinergics.

Pharmacokinetics

Pharmacokinetics

• Absorption: Extremely low systemic absorption after inhalation (< 10%). Being a highly ionized molecule with a positive charge (quaternary ammonium), it does not easily cross the gastrointestinal membranes or the blood-brain barrier.
• Onset of action: 15 - 30 minutes (slower than SABA). Maximum effect at 1.5 - 2 hours.
• Metabolism: Partially metabolized by hydrolysis of esters to inactive metabolites.
• Excretion: Renal for the minimum fraction absorbed; The unabsorbed portion is eliminated unchanged in feces.
• Half-life: Duration of clinical action 4 - 6 hours.

Indicators and dose

Dosage and Clinical Adjustment

• Asthma crisis / COPD (pMDI 20 µg/puff): 2 to 4 inhalations every 6 hours or as needed.
• Nebulization (0.025% solution, 250 - 500 µg): Administer every 4-6 hours diluted in sterile saline, in combination with SABA.

Security

Contraindications and Precautions

• Hypersensitivity to atropine or its derivatives.
• Narrow-angle glaucoma: Accidental ocular impaction of inhaled aerosol causes marked mydriasis and acute increase in intraocular pressure. Strict use of well-fitting masks or mouthpieces is advised.
• Urinary retention and prostatic hyperplasia: Systemic escape of the drug can antagonize the contraction of the detrusor muscle of the bladder mediated by muscarinic receptors.

Clinical

SABA + SAMA Clinical Synergism in Emergencies

The combined use of salbutamol and ipratropium (available in combination solution as Combivent) dramatically reduces hospitalization rates in pediatric and moderate-severe adult asthma attacks compared to SABA monotherapy. This occurs because they address two different and independent metabolic pathways of contraction: the cAMP pathway (adrenergic) and the calcium/IP3 pathway (cholinergic).