Ipratropium bromide

Ipratropium bromide (INN)

Systematic (IUPAC) name
[8-methyl-8-(1-methylethyl)- 8-azoniabicyclo[3.2.1] oct-3-yl] 3-hydroxy-2-phenyl-propanoate
Clinical data
Trade names	Atrovent, Apovent, Ipraxa, Rinatec, other
AHFS/Drugs.com	monograph
Pregnancy category	US: B (No risk in non-human studies)
Legal status	UK: POM (Prescription only) US: ℞-only
Routes of administration	Inhalation
Pharmacokinetic data
Protein binding	0 to 9% in vitro
Metabolism	Hepatic
Biological half-life	2 hours
Identifiers
CAS Number	22254-24-6 Template:CAS (cation)
ATC code	R01AX03 (WHO) R03BB01
PubChem	CID: 657308
IUPHAR/BPS	325
DrugBank	DB00332
ChemSpider	10481997
UNII	GR88G0I6UL Y
ChEMBL	CHEMBL1464005 N
Chemical data
Formula	C20H30BrNO3
Molecular mass	412.37 g/mol
SMILES CC(C)[N+]1([C@@H]2CC[C@H]1C[C@H](C2)OC(=O)C(CO)C3=CC=CC=C3)C.[Br-]
InChI InChI=1S/C20H30NO3.BrH/c1-14(2)21(3)16-9-10-17(21)12-18(11-16)24-20(23)19(13-22)15-7-5-4-6-8-15;/h4-8,14,16-19,22H,9-13H2,1-3H3;1H/q+1;/p-1/t16-,17+,18+,19?,21?; Key:LHLMOSXCXGLMMN-WDTICOSOSA-M
NY (what is this?)  (verify)

Ipratropium bromide, sold under the trade name Atrovent among others, is a medication that opens up the medium and large airways in the lungs. It is used to treat the symptoms of chronic obstructive pulmonary disease and asthma. 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 and breastfeeding. Ipratropium is an anticholinergic which works by causing smooth muscles to relax.

Ipratropium bromide was developed in Germany in 1976. It was approved for medical use in the United States in 1986. It is on the World Health Organization's List of Essential Medicines, the most important medication needed in a basic health system. Ipratropium is available as a generic medication. The wholesale price is about 6.60 USD for a 200 dose inhaler. In the United States a month worth of medication is between 100 and 200 USD.

Medical uses

Ipratropium is administered by inhalation for the treatment of chronic obstructive pulmonary disease (COPD). For that purpose 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.

It is also combined with salbutamol (albuterol, USA) under the trade names Combivent (metered-dose inhaler 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 rhinorrhea but will not help nasal congestion.

Combination with beta-adrenergic agonists, increases the dilating effect on the bronchi.

Contraindications

There are no contraindications for inhaled ipratropium, apart from hypersensitivity to atropine and related substances. For oral administration, contraindications are similar to other anticholinergics; they include narrow angle glaucoma and obstructions in the gastrointestinal tract and urinary system.

Peanut allergy

Previously atrovent inhalers used chlorofluorocarbon (CFC) as a propellant and contained soy lecithin in the propellant ingredients. In 2008 all CFC inhalers were phased out and hydrofluoroalkane (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 antidepressants, antiparkinson drugs and quinidine, which theoretically increase side effects, are clinically irrelevant when ipratropium is administered as an inhalant.

Pharmacology

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 (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 secretion. It is a nonselective muscarinic 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 (anticholinergic syndrome). Ipratropium is not considered a short-acting bronchodilator and should never be used in place of albuterol (salbutamol) as a rescue medication.

See also

• Tiotropium bromide
• Epinephrine
• Beclometasone dipropionate
• Salbutamol
• Ipratropium/salbutamol