Duavent Mechanism of Action

Pharmacology: Pharmacodynamics: Ipratropium bromide is an anticholinergic bronchodilator that reduces the formation of cyclic guanosine monophosphate (cGMP), a mediator of bronchospasm, thereby relaxing the smooth muscles of the bronchi and bronchioles. It is a potent bronchodilator, particularly in large bronchial airway; some evidence suggests that Ipratropium bromide also has bronchodilator activity in small airways.
Salbutamol is a selective short-acting beta₂-adrenergic agonist with preferential effect on beta₂-adrenergic receptors found in the respiratory tract. It stimulates adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). cAMP mediates cellular responses such as bronchial smooth muscle relaxation resulting in bronchodilation.
Ipratropium bromide-Salbutamol combination maximizes the response to treatment in patients with bronchial asthma and chronic obstructive pulmonary disease (COPD) by increasing bronchodilation through two distinctly different mechanisms, i.e., anticholinergic (parasympatholytic) and beta₂-agonist (sympathomimetic) effects. Simultaneous administration of both an anticholinergic (Ipratropium bromide) and a beta₂-agonist (Salbutamol) produces a greater bronchodilator effect than when either drug is used alone.
Bronchodilation occurs within 15 to 30 minutes with peak effect seen approximately 1 to 2 hours after oral inhalation via nebulization of 400 to 600 mcg of Ipratropium bromide. Bronchodilation generally persists for 4 to 5 hours, but may last up to 7 to 8 hours in some patients.
After concomitant administration via nebulization of Salbutamol and Ipratropium in patients with COPD, bronchodilation persists for 5 to 7 hours compared with 3 to 4 hours in patients given Salbutamol alone.
Pharmacokinetics: Pulmoneb: Only a small amount of Ipratropium reaches the systemic circulation after inhalation. Some Ipratropium is inadvertently swallowed but it is poorly absorbed from the gastrointestinal tract.
Pharmacokinetic studies in asthmatic patients receiving Salbutamol inhalation solution indicate that less than 20% of a single dose of the drug is absorbed when administered by nebulization. The remainder of the dose was recovered from the nebulizer and expired air.
Ipratropium is 0 to 9% bound to plasma albumin and α₁-acid glycoproteins in vitro. It is partially metabolized to N-isopropylnortropium methobromide, an inactive ester hydrolysis product.
Salbutamol is metabolized in the liver, being converted to Salbutamol 4'-O-sulfate which has little or no beta-adrenergic stimulating effect and no beta-adrenergic blocking effect.
Animal studies show that Salbutamol can cross the blood-brain barrier and the placenta. It may be secreted in breast milk, but the concentrations are not known.
Metered-Dose Inhaler: After oral inhalation of ipratropium bromide-salbutamol sulfate combination in patients with COPD, the onset of bronchodilation is evident within 15 min, with peak effect in 1 hr. Bronchodilation persists for 4-5 hrs with the combination compared with 4 hrs with ipratropium bromide alone and 3 hrs for salbutamol alone. Ipratropium's peak plasma concentration remains below detectable limits (<100 pg/mL) while maximum salbutamol concentration is 492 pg/mL occurring within 3 hrs after administration; 27.1% of the estimated mouthpiece dose of ipratropium-salbutamol combination is excreted in urine as unchanged drug within 24 hrs.
Ipratropium is 0-9% bound to plasma albumin and α₁-acid glycoproteins in vitro. It is partially metabolized to N-isopropylnortropium methobromide, an inactive ester hydrolysis product.
Salbutamol is metabolized in the liver, being converted to salbutamol 4'-O-sulfate which has little or no β-adrenergic stimulating effect and no β-adrenergic blocking effect.
Animal studies show that salbutamol can cross the blood-brain barrier and the placenta. It may be secreted in breast milk, but the concentrations are not known.