Tiotropium bromide, sold under the brand name Spiriva among others, is a long-acting

bronchodilator A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lun ...

(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 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 ...

. 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 Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are ...

, worsening

bronchospasm Bronchospasm or a bronchial spasm is a sudden bronchoconstriction, constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylat ...

, and QT prolongation. Tentative evidence has not found harm during

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 ...

, however, such use has not been well studied. It is an

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 and works by blocking

acetylcholine Acetylcholine (ACh) is an organic compound 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. Par ...

action on

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 ...

. Tiotropium was patented in 1989, and approved for medical use in 2002. 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 ...

. In 2022, it was the 154th most commonly prescribed medication in the United States, with more than 3million 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 or acute worsening of asthma. Tiotropium is also used in a combination inhaler with olodaterol, 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 A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...

effects. Common

adverse drug reaction An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or may result from the combination of two or more drugs. The meaning of this ...

s (≥1% of people) include: dry mouth and/or throat irritation. Rarely (<0.1% of patients) treatment is associated with:

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 ...

, 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 Atrial fibrillation (AF, AFib or A-fib) is an Heart arrhythmia, abnormal heart rhythm (arrhythmia) characterized by fibrillation, rapid and irregular beating of the Atrium (heart), atrial chambers of the heart. It often begins as short periods ...

) and allergy (rash,

anaphylaxis Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...

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

Mechanism of action

Tiotropium is a

muscarinic receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...

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.antimuscarinic A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...

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

y 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 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

{{Portal bar , Medicine Bromides Bronchodilators Drugs developed by Boehringer Ingelheim Drugs developed by Pfizer Epoxides M1 receptor antagonists M2 receptor antagonists M3 receptor antagonists M4 receptor antagonists M5 receptor antagonists Quaternary ammonium compounds Tertiary alcohols Thiophenes World Health Organization essential medicines Wikipedia medicine articles ready to translate