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 acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

medication which is applied by different routes:

inhaler An inhaler (puffer, asthma 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 provides the ...

nebulizer In medicine, a nebulizer (American English) or nebuliser (English language, 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, c ...

, or

nasal spray Nasal sprays are used to deliver medications Route of administration#Local, locally in the nasal cavities or systemic administration, systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some sit ...

, for different reasons.Rx.com: Ipratropium
/ref> The inhalant 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 chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...

(COPD) and

asthma Asthma is a common 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 wh ...

. It is used by

. Onset of action is typically within 15 to 30 minutes and lasts for three to five hours. The nasal spray prevents the glands in the nose from producing large amounts of fluid.Mayo Clinic: Ipratropium (Nasal Route)
/ref>Cleveland Clinic: Ipratropium Nasal Spray
/ref> It is used to treat

rhinorrhea Rhinorrhea (American English), also spelled rhinorrhoea or rhinorrhœa (British English), or informally runny nose is the free discharge of a thin mucus fluid from the nose; it is an extremely common condition. It is a common symptom of allergie ...

(runny nose) caused by

allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. It is classified as a type I hypersensitivity reaction. Signs a ...

, nonallergic rhinitis, and the common cold.Rxlist.com: Atrovent Nasal Spray
/ref> It is used by metered-dose manual pump spray. Onset of action is within an hour. Common side effects of inhalant use include

dry mouth Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause. This symptom is very common and is o ...

cough A cough is a sudden expulsion of air through the large breathing passages which can help clear them of fluids, irritants, foreign particles and Microorganism, microbes. As a protective reflex, coughing can be repetitive with the cough reflex fol ...

, inflammation of the airways, and

shortness of breath Shortness of breath (SOB), known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that con ...

.RxList.com: Atrovent HFA
/ref> 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 urinary incont ...

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

and

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

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

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

s to relax. Common side effects of nasal spray may include

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, dry nose, dry mouth or throat, nasal or throat irritation, nosebleeds, bad taste in mouth,

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

, or

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...

. Potentially serious side effects are unusual, but include severe allergic reaction, eye pain or change in vision, or urinary retention. It is considered safe during pregnancy, but it can pass into breast milk and may harm a nursing baby.Drugs.com: Ipratropium nasal
/ref> 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 A health system, health care system or healthcare system is an organization of people, institutions, and resources that delivers health care services to meet the health needs of target populations. There is a wide variety of health systems aroun ...

. Ipratropium is available as a generic medication. In 2022, it was the 219th most commonly prescribed medication in the United States, with more than 1million prescriptions.

Medical uses

Ipratropium as an inhalant can be used for the treatment of

(COPD) and

exacerbation. It is supplied in a canister for use in an

or in single dose vials for use in a

. 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 Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, causing widening of the airways and resulting in easier breathing. They are a class of sympathomimetic agents, each acting upon the Adrenergic receptor# ...

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 that causes relaxation of ...

— USAN) 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 (nebulizer) for the management of COPD and asthma, 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

(runny nose) but will not help

nasal congestion Nasal congestion is the partial or complete blockage of nasal passages, leading to impaired nasal breathing, usually due to membranes lining the nose becoming swollen from inflammation of blood vessels. Background In about 85% of cases, nasal ...

. It is supplied in a metered-dose manual pump spray.

Contraindications

The main contraindication for ipratropium in any form is

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes Imm ...

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 give ...

and related substances. Conditions such as narrow-angle glaucoma, prostatic hyperplasia, or bladder neck obstruction are not necessarily contraindicators, but should be taken into account, particularly if the patient is receiving an anticholinergic by another route.

Peanut allergy

Previously, Atrovent inhalers used

chlorofluorocarbon Chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are fully or partly Halogenation, halogenated hydrocarbons that contain carbon (C), hydrogen (H), chlorine (Cl), and fluorine (F). They are produced as volatility (chemistry), volat ...

(CFC) as a propellant and contained soy lecithin in the propellant ingredients. In 2008 all CFC inhalers were phased out and

hydrofluoroalkane Organofluorine chemistry describes the chemistry of organofluorine compounds, organic compounds that contain a carbon–fluorine bond. Organofluorine compounds find diverse applications ranging from Lipophobicity, oil and hydrophobe, water repell ...

(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,

and

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

have been reported. Also, effects such as skin flushing,

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

, acute angle-closure

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

palpitations Palpitations occur when a person becomes aware of their heartbeat. The heartbeat may feel hard, fast, or uneven in their chest. Symptoms include a very fast or irregular heartbeat. Palpitations are a sensory symptom. They are often described as ...

, and

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 respiratory tract, airways in the respiratory system. It is one of the two protective processes for the lungs in removi ...

. 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. Common side effects of nasal spray are experienced at a rate of 1-6% (versus the control group of 0-3%), and may include headache, dry nose, dry mouth or throat, nasal or throat irritation, nosebleeds, bad taste in mouth, nausea,

, or

. Potentially serious side effects from nasal spray are rare, but include severe allergic reaction, eye pain or change in vision, or difficulty urinating. Accidental contact with the eye should be avoided.

Interactions

Interactions with other anticholinergics like

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...

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 a diastereomer 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. Ipratropium nasal spray may interact with certain medications for depression,

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

, or other mental health conditions, certain medications for

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

such as

benztropine Benzatropine ( INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is ...

and trihexyphenidyl,

, certain

antihistamines Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides r ...

for

allergy Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

, and

cold Cold is the presence of low temperature, especially in the atmosphere. In common usage, cold is often a subjectivity, subjective perception. A lower bound to temperature is absolute zero, defined as 0.00K on the Kelvin scale, an absolute t ...

, certain medications for bladder problems such as oxybutynin and tolterodine, certain medications for stomach problems such as

dicyclomine Dicycloverine, also known as dicyclomine, sold under the brand name Bentyl among others, is a medication that is used to treat spasms of the intestines such as those that occur in irritable bowel syndrome (IBS). It is taken by mouth or by inje ...

and

hyoscyamine Hyoscyamine (also known as daturine or duboisine) is a naturally occurring tropane alkaloid and plant toxin. It is a secondary metabolite found in certain plants of the family Solanaceae, including Hyoscyamus niger, henbane, Mandragora officina ...

, and certain medications for motion sickness such as

scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin a ...

Pharmacology

Chemically, ipratropium bromide is a quaternary ammonium compound (which is indicated by the -ium per the BAN 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 ''Datura stramonium'', known by the common names thornapple, jimsonweed (jimson weed), or devil's trumpet, is a poisonous flowering plant in the ''Datureae, Daturae'' Tribe (botany), tribe of the nightshade family Solanaceae. Its likely origi ...

'', 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 ...

(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 bei ...

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 fluid, serous and muc ...

secretion 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 classical mec ...

. It is a nonselective

muscarinic A muscarinic acetylcholine receptor agonist, also simply known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, lab ...

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. 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 membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

, which prevents central side effects. 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 that causes relaxation of ...

(albuterol) as a rescue medication.

References

{{DEFAULTSORT:Ipratropium Bromide Drugs developed by Boehringer Ingelheim Bromides Bronchodilators Isopropylamino compounds M1 receptor antagonists M2 receptor antagonists M3 receptor antagonists M4 receptor antagonists M5 receptor antagonists Primary alcohols Carboxylate esters Quaternary ammonium compounds Tropanes World Health Organization essential medicines Wikipedia medicine articles ready to translate