Tiotropium bromide, sold under the brand name Spiriva among others, is a long-acting bronchodilator (LAMA: long acting muscarinic antagonist) used in the management 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 ...

(COPD) 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, cou ...

. Specifically it is used during periods of breathing difficulty to prevent them from getting worse, rather than to prevent them from happening. It is used by inhalation through the mouth. Onset typically begins within half an hour and lasts for 24 hours. Common side effects include a dry mouth, runny nose, upper respiratory tract infection, shortness of breath and headache. Severe side effects may include angioedema, worsening bronchospasm, and

QT prolongation Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, ...

. Tentative evidence has not found harm during

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 ca ...

, however, such use has not been well studied. It is an anticholinergic medication and works by blocking

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

action on

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 mus ...

. Tiotropium was patented in 1989, and approved for medical use in 2002. It is on the World Health Organization's List of Essential Medicines. In 2020, it was the 110th most commonly prescribed medication in the United States, with more than 5million prescriptions.

Medical uses

Tiotropium is used as maintenance treatment of

(COPD). It may also be used as an add-on therapy in people with moderate-to-severe asthma on medium to high dose inhaled corticosteroids (ICS). It is not however approved for

acute exacerbations of COPD An acute exacerbation of chronic obstructive pulmonary disease, or acute exacerbations of chronic bronchitis (AECB), is a sudden worsening of chronic obstructive pulmonary disease (COPD) symptoms including dyspnea, shortness of breath, quantity an ...

or acute worsening of asthma. Tiotropium is also used in a combination inhaler with

olodaterol Olodaterol (trade name Striverdi Respimat) is an ultra- long-acting β adrenoreceptor agonist (ultra-LABA) used as an inhalation for treating people with chronic obstructive pulmonary disease (COPD). It is manufactured by Boehringer Ingelheim.Stri ...

, a long-acting beta-agonist, for the treatment of COPD, under the brand names ''Stiolto'' and ''Spiolto'' among others.

Adverse effects

Adverse effects are mainly related to its antimuscarinic effects. Common adverse drug reactions (≥1% of people) include: dry mouth and/or throat irritation. Rarely (<0.1% of patients) treatment is associated with: urinary retention, constipation, acute angle closure glaucoma, palpitations (notably

supraventricular tachycardia Supraventricular tachycardia (SVT) is an umbrella term for fast heart rhythms arising from the upper part of the heart. This is in contrast to the other group of fast heart rhythms – ventricular tachycardia, which start within the lower cham ...

and atrial fibrillation) and allergy (rash, angioedema,

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

). A 2006 review found the increase in bronchospasm was small and did not reach statistical significance. Data regarding some serious side effects is mixed as of 2020. In September 2008 a review found that tiotropium and another member of its class

ipratropium 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 ...

may be linked to increased risk of heart attacks, stroke and cardiovascular death. The US FDA reviewed the concern and concluded in 2010 that this association was not supported. A 2011 review of the tiotropium mist inhaler (

Respimat Respimat, also known as Respimat Soft Mist Inhaler, is a drug delivery device used for the treatment of asthma, chronic obstructive pulmonary disease (COPD), and other respiratory conditions. Its developer, Boehringer Ingelheim, is currently cond ...

); however, still found an associated with an increase in all cause mortality in people with COPD.

Mechanism of action

Tiotropium is a

muscarinic receptor 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 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, riv ...

, often referred to as an antimuscarinic or anticholinergic agent. Although it does not display selectivity for specific muscarinic receptors, when topically applied it acts mainly on M₃ muscarinic receptors located on smooth muscle cells and submucosal glands. This leads to a reduction in

contraction and mucus secretion and thus produces a bronchodilatory effect.

Society and culture

Tiotroprium is available in two inhaler formats: a soft mist inhaler (''Respimat'') and a dry powder inhaler (''HandiHaler''). The safety and efficacy profiles of both devices are comparable and people's preference should play a role in determining inhaler choice. There is no significant difference in all-cause

mortality Mortality is the state of being mortal, or susceptible to death; the opposite of immortality. Mortality may also refer to: * Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...

between tiotropium soft mist inhalers compared to dry powder inhalers, however caution needs to be taken in people with severe heart or kidney problems. Image:Spiriva3.png Image:"Spiriva HandiHaler"-brand dry powder inhaler (open).png

References

External links

* * {{Portal bar , Medicine Boehringer Ingelheim Bromides Bronchodilators Epoxides Muscarinic antagonists Pfizer brands Quaternary ammonium compounds Tertiary alcohols Thiophenes World Health Organization essential medicines Wikipedia medicine articles ready to translate