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Active Ingredient of Atrovent



Therapeutic indications of Atrovent 

Ipratropium bromide treats reversible bronchospasm associated with chronic obstructive pulmonary disease (COPD).

Ipratropium bromide with inhaled beta2-agonists treats reversible airways obstruction as in acute and chronic asthma.


Mechanism of Action of Atrovent

Ipratropium bromide is a quaternary ammonium compound with anticholinergic (parasympatholytic) properties. In nonclinical studies, it appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve.

Anticholinergics prevent the increase in intracellular concentration of Ca++ which happens due to interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle. Ca++ release is mediated by the second messenger system consisting of IP3 (inositol triphosphate) and DAG (diacylglycerol).

The bronchodilation following inhalation of ipratropium bromide happens by local drug concentrations sufficient for anticholinergic efficacy at the bronchial smooth muscle and not by systemic drug concentrations.

In clinical trials using metered dose inhalers in patients with reversible bronchospasm associated with chronic obstructive pulmonary disease significant improvements in pulmonary function (FEV1 increases of 15% or more) occurred within 15 minutes, reached a peak in 1-2 hours, and persisted for approximately 4 hours.

Preclinical and clinical evidence suggest no deleterious effect of ipratropium bromide on airway mucous secretion, mucociliary clearance or gas exchange.

The bronchodilator effect of ipratropium bromide in the treatment of acute bronchospasm with asthma has been shown in studies in adults and children ≥ 6 years of age. In most of these studies ipratropium bromide was administered in combination with an inhaled beta2-agonist.


Side effects of Atrovent

Uncommon (may affect up to 1 in 100 people):

  • If after using Ipratropium Bromide Nebulizer Solution you are wheezy or have

other difficulties in breathing, do not use any more (unless you have been told to

by your doctor).

  • Allergic reactions – the signs may include skin rash and itching. In severe

cases the signs include swelling of your mouth and face, sudden difficulties in

breathing and reduction of your blood pressure. Tightening of your throat.

  • Palpitations (fast or uneven heart beats) or quickening of the heart rate.

Rare (may affect up to 1 in 1,000 people):

  • Increased heart rate or irregular heart rhythm such as atrial fibrillation.

Other side effects include:

Common (may affect up to 1 in 10 people):

  • Headache, dizziness
  • Cough and throat irritation.
  • Dry mouth
  • Nausea (feeling sick), stomach upset or discomfort.


Drug Interactions with Atrovent

The chronic co-administration of ipratropium bromide inhalation with other anticholinergic drugs has no clear studies. Therefore, don’t take ipratropium with other anti-cholinergic drugs.

There is evidence that the administration of ipratropium bromide with beta-adrenergic drugs and xanthine preparations may produce an additive bronchodilator effect.

It may increase the risk of acute glaucoma in patients with a history of narrow-angle glaucoma when nebulized ipratropium bromide and beta2-agonists.


Pharmacokinetic properties of Ipratropium 


The therapeutic effect of ipratropium bromide occurs by producing local action in the airways. Time courses of bronchodilation and systemic pharmacokinetics do not run in parallel.

Following inhalation, 10 to 30% of a dose is generally deposited in the lungs, depending on the formulation, device and inhalation technique. The major part of the dose is swallowed and passes through the gastro-intestinal tract.

The portion of the dose deposited in the lungs reaches the circulation rapidly (within minutes).

Cumulative renal excretion (0-24 hrs.) of the parent compound is about 46% of an intravenously  dose, below 1% of an oral dose and approximately 3 to 13% of a dose by inhalation. Based on these data the total systemic bioavailability of oral and  doses by inhalation of ipratropium bromide is around 2% and 7 to 28% respectively.

Taking this into account, oral dose portions of ipratropium bromide do not contribute significantly to systemic exposure.


The drug is minimally (less than 20%) bound to plasma proteins. Nonclinical data indicate that the quaternary amine ipratropium does not cross the placental or the blood-brain barrier.



Ipratropium has a mean total clearance of 2.3 L/min and a renal clearance of 0.9 L/min.

In an excretion balance study cumulative renal excretion (6 days) of drug-related radioactivity (including parent compound and all metabolites) accounted for 72.1% after intravenous administration, 9.3% after oral administration and 3.2% after inhalation. Total radioactivity excreted via the faeces was 6.3% following intravenous application, 88.5% following oral dosing and 69.4% after inhalation. Regarding the excretion of drug-related radioactivity after intravenous administration, the main excretion occurs via the kidneys. The half-life for elimination of drug-related radioactivity (parent compound and metabolites) is 3.2 hours.


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