Ipratropium bromide, sold under the trade name Atrovent among others, is a type of

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous sys ...

(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 An inhaler (also known as a puffer, pump or allergy spray) is a medical device used for delivering medicines into the lungs through the work of a person's breathing. This allows medicines to be delivered to and absorbed in the lungs, which prov ...

nebulizer In medicine, a nebulizer (American English) or nebuliser (British English) is a drug delivery device used to administer medication in the form of a mist inhaled into the lungs. Nebulizers are commonly used for the treatment of asthma, cystic fibro ...

. 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 Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladd ...

, 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 (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

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 br ...

. Ipratropium is a short-acting

muscarinic antagonist A muscarinic receptor antagonist (MRA) is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. The muscarinic receptor is a protein involved in the transmission of signals through certain parts of the ...

, which works by causing smooth muscles 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 WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

, the most important medicines needed in a health system. 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 Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine in ...

increases the dilating effect on the bronchi, as when ipratropium is combined with salbutamol (

albuterol 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 ...

—

USAN 280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk（于山國）was Ulleungdo（鬱陵島） Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to th ...

) under the trade names Combivent (a non-aerosol

metered-dose inhaler A metered-dose inhaler (MDI) is a device that delivers a specific amount of medication to the lungs, in the form of a short burst of aerosolized medicine that is usually self-administered by the patient via inhalation. It is the most commonly used ...

or MDI) and Duoneb (

) for the management of

COPD 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

, and with

fenoterol Fenoterol is a β adrenoreceptor agonist. It is classed as sympathomimetic β2 agonist and an inhaled bronchodilator asthma medication. Fenoterol is produced and sold by Boehringer Ingelheim as Berotec N and in combination with ipratropium as ...

(trade names Duovent and Berodual N) for the management of asthma. Ipratropium as a nasal solution sprayed into the nostrils can reduce

rhinorrhea Rhinorrhea, rhinorrhoea, or informally runny nose is the free discharge of a thin mucus fluid from the nose; it is a common condition. It is a common symptom of allergies ( hay fever) or certain viral infections, such as the common cold or CO ...

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 ...

to atropine 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 fluid within the eye rem ...

and obstructions in the gastrointestinal tract and

urinary system The urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, c ...

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 pro ...

(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 a ...

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

s 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 Mucociliary clearance (MCC), mucociliary transport, or the mucociliary escalator, describes the self-clearing mechanism of the airways in the respiratory system. It is one of the two protective processes for the lungs in removing inhaled particl ...

. 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 Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...

, 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 and the

) obtained by treating atropine with isopropyl bromide, thus the name: isopropyl + atropine. It is chemically related to components of the plant ''

Datura stramonium ''Datura stramonium'', known by the common names thorn apple, jimsonweed (jimson weed), devil's snare, or devil's trumpet, is a poisonous flowering plant of the nightshade family Solanaceae. It is a species belonging to the ''Datura'' genus a ...

'', 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 in r ...

(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 Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. Causes The condition has a number of causes, the most common be ...

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. It is a nonselective

muscarinic Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

antagonist, and does not diffuse into the blood, which prevents systemic side effects. Ipratropium is a derivative of atropine but is a quaternary amine and therefore does not cross the blood–brain barrier, which prevents central side effects (e.g., anticholinergic syndrome). Ipratropium should never be used in place of salbutamol (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