Ipratropium

Mechanism of Action

Ipratropium is an acetylcholine antagonist via blockade of muscarinic cholinergic receptors. Blocking cholinergic receptors decreases the production of cyclic guanosine monophosphate (cGMP). This decrease in the lung airways will lead to decreased contraction of the smooth muscles. The actions of intranasal ipratropium mimic the action of atropine by inhibiting salivary and mucous glands secretions as well as dilating bronchial smooth muscle.

Compared to atropine, orally inhaled ipratropium is a more potent antimuscarinic and bronchial dilator of smooth muscle.

Intranasal ipratropium produces a local parasympathetic response, leading to decreased water secretions of mucosal glands of the nasal system alleviating symptoms of rhinorrhea (allergic or non-allergic).[1]

Studies showed that the mean peak percent increases in FEV1 over baseline were 24 to 25 percent for oral inhaled ipratropium in COPD patients. This research noted similar changes in forced vital capacity curves. However, when given via metered-dose inhaler to patients with COPD, the combination of ipratropium and albuterol proved more effective than either of the two agents alone.[2]

Administration

The administration of ipratropium is via inhalation, either orally or intranasally.

Oral Inhalation

The oral formulation can be aerosol inhalation or a solution for nebulization.

Aerosol Inhalation

If the patient experiences difficulty inhaling the drug after actuation, they can use a valved holding chamber (VHC) or a spacer. A patient can choose between a mouthpiece or a face mask along with the VHC or spacer based on patient convenience. Usually, it is more convenient for patients under the age of 4 to use a tight face mask, and VHC or spacer get the most from treatment. When using a face mask, the patient should be instructed to inhale 3 to 5 times per actuation. After administration patient is to be instructed to rinse the mouth with water to decrease the side effect of mouth dryness. Patients should be instructed not to use other persons' inhalers to prevent the transfer of any possible infections.[3]

Dosage

Adults: 

• 17 mcg per spray
• COPD: 2 sprays every 6 hours
• Asthma exacerbation, moderate to severe: 8 sprays every 20 mins as needed for up to 3 hours
• No renal impairment adjustment is necessary.

Pediatrics: 

• NEB (0.02%): 0.25 mg every 20 mins up to 3 doses for moderate to severe asthma exacerbation: if less than 6 years old.
• NEB (0.02%): 0.25 to 0.5 mg every 20 mins as needed up to 3 hours for moderate to severe asthma exacerbation: age 6 to 12 years old.
• NEB (0.02%): 0.5 mg every 20 mins as needed up to 3 hours for moderate to severe asthma exacerbation: if age 13 years old or above.

Solution for Nebulization

Ipratropium can be mixed with albuterol formations in the same nebulizer within one hour of use. On the other hand, ipratropium should not be mixed with cromolyn solutions as both are incompatible.

Intranasal Inhalation

Nasal Spray Solution

• Prime the unit before using it for the first time.
• Point the sprayer away from patients or other persons/animals.
• Push the activator 6 to 7 pushes until a wide and fine spray is observed.
• After that, if the unit remains unused for over 24 hours, then prime the unit again by pushing the pump at least twice before use. If the unit remains unused for more than 7 days, then prime the unit again by pushing the pump seven times all over again.
• Patients should be instructed not to use other peoples' inhalers to prevent the transfer of any possible infections.[2]

Dosage

• 0.03% solution: 21 mcg/spray
• 0.06% solution: 42 mcg/spray
• Rhinorrhea (allergic or nonallergic rhinitis): 2 sprays of 0.03% solution per nostril every 6 hours. Seasonal allergic rhinitis: 2 sprays of 0.06% per nostril every 6 hours or every 8 hours.
• Common cold: 2 sprays of 0.06% per nostril every 6 hours or every 8 hours
• No renal impairment adjustment is necessary.

Adverse Effects

Ipratropium Inhaled

Most common adverse reactions:

• Bronchitis
• Nausea
• Mouth dryness
• Skin flushing
• Dyspnea
• Symptoms of a common cold
• Dizziness
• Sinusitis
• Dyspepsia
• Back pain
• UTI
• Tachycardia
• Arrhythmias
• Severe adverse reactions:
• Hypersensitivity reaction
• Paradoxical bronchospasms
• Anaphylaxis
• Closed-angle glaucoma

Ipratropium Intranasal

Most common adverse reactions:

• Upper respiratory infections
• Epistaxis
• Pharyngitis
• Headache
• Xerostomia
• Change of taste
• Nausea
• Nasal irritation
• Arrhythmias

Severe adverse reactions[4]:

• Hypersensitivity reaction
• Anaphylaxis

Contraindications

Contraindications to ipratropium inhaler use include patients that are hypersensitive to atropine; this is secondary to the similarity in structure to atropine.[5]

Ipratropium aerosols can cause bronchospasms (paradoxical), which usually happens upon the initial use of this medication. Patients should understand this possibility. If this adverse reaction occurs, then this medication should be immediately discontinued.

Previous severe allergic reaction symptoms upon using ipratropium or atropine and its other derivatives, such as angioedema, urticaria, severe shortness of breath, oropharyngeal edema, and ultimately anaphylaxis is a contraindication to ipratropium use.

Caution is necessary for the use of intranasal/inhaled ipratropium in patients with hypertrophic prostate.[6]

Exercise caution with the use of intranasal/inhaled ipratropium in patients with obstruction of the bladder neck.[1]

Caution is recommended in the use of intranasal/inhaled ipratropium in patients with closed-angle glaucoma.[1]

Ipratropium is labeled as category B regarding pregnancy since there are no reports of teratogenesis in animals or humans with ipratropium use (aerosols or nasal spray), but studies in humans are limited. Ipratropium should only be used during pregnancy if the mother's benefits outweigh possible fetus risks.[1]

Monitoring

Ipratropium inhalation aerosol is a bronchodilator agent for chronic control of bronchospasms secondary to COPD and not a first-line medication for acute bronchospasms and not used as a rapid response agent for acute situations.

Symptoms of anaphylaxis (angioedema, urticaria, bronchospasms, rash) should be monitored, especially upon the first use of this medication. As mentioned above, if these symptoms occur, the drug should be discontinued.[7]

As mentioned above, caution is necessary for patients with prostatic hypertrophy, bladder neck obstruction, and closed-angle glaucoma.[8]

There are no recommended routine monitoring tests.

Toxicity

High doses of ipratropium can cause toxicity similar to anticholinergic toxicity symptoms.[9][10]

These symptoms include:

• Hyperthermia
• Agitation
• Confusion
• Mydriasis
• Mucosal dryness
• Reports have demonstrated ipratropium worsens ischemic injuries in nonclinical settings.

Enhancing Healthcare Team Outcomes

Ipratropium is a bronchodilator widely used for chronic obstructive pulmonary diseases. This drug is known to relieve bronchospasms and enhance patency of airways in the lungs. To prescribe this medication requires proper communication between healthcare providers and pharmacists and subspecialty doctors such as pulmonologists. An interprofessional approach can effectively monitor drug efficacy and adjust the dosing and combination of this agent with other agents acting on the airways. Although most of the situations are perfectly manageable via one healthcare provider. This medication can sometimes work in combination with other agents that act on the airways, but in some instances, it could be incompatible for use with other agents using the same nebulizer. Hence it is essential to obtain drug-drug interactions via pharmacists. It is critical to document any previous adverse reaction if this medication was used before, such as hypersensitivity reactions or anaphylaxis. Pharmacists should flag a prescription if those adverse reactions have been previously charted and immediately notify the healthcare providers and patients.[4]

In summary, the successful implementation of ipratropium therapy requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level 5]