Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic (SAMA: short acting muscarinic antagonist) medication which opens up the medium and large airways in the lungs. It is used to treat the symptoms of

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

and

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...

. It is used by inhaler or nebulizer. Onset of action is typically within 15 to 30 minutes and lasts for three to five hours. Common side effects include dry mouth, cough, and inflammation of the airways. Potentially serious side effects include urinary retention, worsening spasms of the airways, and a severe allergic reaction. It appears to be safe in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

and

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...

. Ipratropium is a short-acting muscarinic antagonist, which works by causing

smooth muscle Smooth muscle is an involuntary non- striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit ...

s to relax. Ipratropium bromide was patented in 1966, and approved for medical use in 1974. It is on the World Health Organization's List of Essential Medicines, the most important medicines needed in a

health system Health, according to the World Health Organization, is "a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity".World Health Organization. (2006)''Constitution of the World Health Organi ...

. Ipratropium is available as a generic medication. In 2020, it was the 312th most commonly prescribed medication in the United States, with more than 900thousand prescriptions.

Medical uses

Ipratropium is administered by inhalation for the treatment of

(COPD) and asthma exacerbation. It is supplied in a canister for use in an inhaler or in single dose vials for use in a nebulizer. It is also used to treat and prevent minor and moderate bronchial asthma, especially asthma that is accompanied by cardiovascular system diseases, as it has been shown to produce fewer cardiovascular side effects. Combination with beta-adrenergic agonists increases the dilating effect on the bronchi, as when ipratropium is combined with salbutamol ( albuterol — USAN) under the trade names Combivent (a non-aerosol metered-dose inhaler or MDI) and Duoneb ( nebulizer) for the management of COPD and

, and with fenoterol (trade names Duovent and Berodual N) for the management of asthma. Ipratropium as a nasal solution sprayed into the nostrils can reduce rhinorrhea but will not help nasal congestion.

Contraindications

The main contraindication for inhaled ipratropium is

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune ...

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given ...

and related substances. For oral administration, contraindications are similar to other anticholinergics; they include narrow angle

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for aqueous humor, fluid withi ...

and obstructions in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

and urinary system.

Peanut allergy

Previously atrovent inhalers used

chlorofluorocarbon Chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are fully or partly halogenated hydrocarbons that contain carbon (C), hydrogen (H), chlorine (Cl), and fluorine (F), produced as volatile derivatives of methane, ethane, and p ...

(CFC) as a propellant and contained

soy lecithin Lecithin (, from the Greek ''lekithos'' "yolk") is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues which are amphiphilic – they attract both water and fatty substances (and so ar ...

in the propellant ingredients. In 2008 all CFC inhalers were phased out and

hydrofluoroalkane Organofluorine chemistry describes the chemistry of the organofluorines, organic compounds that contain the carbon–fluorine bond. Organofluorine compounds find diverse applications ranging from oil and water repellents to pharmaceuticals, refri ...

(HFA) inhalers replaced them. Allergy to peanuts was noted for the inhaler as a contraindication but now is not. It has never been a contraindication when administered as a nebulized solution.

Side effects

If ipratropium is inhaled, side effects resembling those of other anticholinergics are minimal. However, dry mouth and sedation have been reported. Also, effects such as skin flushing, tachycardia, acute angle-closure glaucoma, nausea, palpitations and headache have been observed. Inhaled ipratropium does not decrease mucociliary clearance. The inhalation itself can cause headache and irritation of the throat in a few percent of patients. Urinary retention has been reported in patients receiving doses by nebulizer. As a result, caution may be warranted, especially by men with prostatic hypertrophy.

Interactions

Interactions with other anticholinergics like

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

s, anti-Parkinson drugs and quinidine, which theoretically increase side effects, are clinically irrelevant when ipratropium is administered as an inhalant.

Pharmacology

Chemically, ipratropium bromide is a quaternary ammonium compound (which is indicated by the -ium per the

BAN Ban, or BAN, may refer to: Law * Ban (law), a decree that prohibits something, sometimes a form of censorship, being denied from entering or using the place/item ** Imperial ban (''Reichsacht''), a form of outlawry in the medieval Holy Roman ...

and the USAN) obtained by treating

with isopropyl bromide, thus the name: isopropyl + atropine. It is chemically related to components of the plant '' Datura stramonium'', which was used in ancient India for asthma. Ipratropium exhibits broncholytic action by reducing cholinergic influence on the bronchial musculature. It blocks muscarinic acetylcholine receptors, without specificity for subtypes, and therefore promotes the degradation of

cyclic guanosine monophosphate Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases ...

(cGMP), resulting in a decreased intracellular concentration of cGMP. Most likely due to actions of cGMP on intracellular calcium, this results in decreased contractility of smooth muscle in the lung, inhibiting bronchoconstriction and

mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It ...

secretion 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classic ...

. It is a nonselective muscarinic

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

, and does not diffuse into the blood, which prevents systemic side effects. Ipratropium is a derivative of

but is a quaternary amine and therefore does not cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where ne ...

, which prevents central side effects (e.g., anticholinergic syndrome). Ipratropium should never be used in place of

salbutamol Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing rel ...

(albuterol) as a rescue medication.

References

External links

* {{portal bar, Medicine Bromides Bronchodilators Isopropyl compounds Muscarinic antagonists Primary alcohols Carboxylate esters Quaternary ammonium compounds Tropanes World Health Organization essential medicines Wikipedia medicine articles ready to translate