Salmeterol (sold in China as Qitai) is a long-acting β₂ adrenergic receptor agonist (LABA) used in the maintenance and prevention of

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 ...

symptoms and maintenance 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) symptoms. Symptoms of

bronchospasm Bronchospasm or a bronchial spasm is a sudden 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 anaphylatoxins. It causes di ...

include

shortness of breath Shortness of breath (SOB), also medically 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 di ...

wheezing A wheeze is a continuous, coarse, whistling sound produced in the respiratory airways during breathing. For wheezes to occur, some part of the respiratory tree must be narrowed or obstructed (for example narrowing of the lower respiratory tract ...

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

ing and chest tightness. It is also used to prevent breathing difficulties during exercise (

exercise-induced bronchoconstriction Exercise-induced asthma, or E.I.A., occurs when the airways narrow as a result of exercise. The preferred term for this condition is exercise-induced bronchoconstriction (EIB). While exercise does not cause asthma, it is frequently an asthma trig ...

). It was patented in 1983 and came into medical use in 1990. It is marketed as Serevent in the US. It is available as a dry-powder inhaler (DPI) that releases a powdered form of the drug. It was previously available as a

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 ...

(MDI) but was discontinued in the US in 2002. It is available as an MDI in other countries as of 2020.

Mechanism of action

Inhaled salmeterol belongs to a group of drugs called beta-2 agonists. These drugs stimulate beta-2 receptors present in the bronchial musculature. This causes them to relax and prevent the onset and worsening of symptoms of asthma. They act on the enzyme adenyl cyclase which increases the concentration of cAMP (

Cyclic adenosine monophosphate Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transd ...

). This cyclic AMP decreases the smooth muscle tone. This drug is 10,000-times more lipid soluble than the short acting beta-2 adrenoceptor agonist, albuterol. Unlike albuterol, salmeterol becomes dissolved in the lipid bilayer of the cell membrane, and its gradual dissociation from the cell membrane provides beta-2 adrenoceptors with a supply of agonist for an extended period of time. The primary noticeable difference of salmeterol from

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 which works by causing rel ...

, and other short-acting β₂ adrenoreceptor agonists (SABAs), is its duration of action. Salmeterol lasts approximately 12 hours in comparison with

, which lasts about 4–6 hours. When used regularly every day as prescribed, inhaled salmeterol decreases the number and severity of asthma attacks. Formoterol has been demonstrated to have a faster onset of action than salmeterol as a result of a lower

lipophilic Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipo ...

ity, and has also been demonstrated to be more potent—a 12 ''µ''g dose of formoterol has been demonstrated to be equivalent to a 50 ''µ''g dose of salmeterol.

Medical uses

* Salmeterol is used in moderate-to-severe persistent asthma following previous treatment with a short-acting β₂ adrenoreceptor agonist (SABA) such as salbutamol (albuterol). * LABAs should not be used as a monotherapy, instead, they should be used concurrently with an inhaled corticosteroid, such as

beclometasone dipropionate Beclomethasone, also known as beclomethasone dipropionate, and sold under the brand name Qvar among others, is a steroid medication. It is available as an inhaler, cream, pills, and nasal spray. The inhaled form is used in the long-term manageme ...

or fluticasone propionate in the treatment of

to minimize serious reactions such as asthma-related deaths. Combination of inhaled corticosteroids and salmeterol (LABA) has synergistic action and reduces the frequency of asthma attacks and also makes it less severe. * In

(COPD), LABAs may be used as monotherapy or in combination with corticosteroids. The Torch study demonstrated benefits in terms of quality of life and lung function of salmeterol alone or in combination with inhaled corticosteroids in patients with COPD * In exercise-induced

monotherapy may be indicated in patients without persistent asthma. LABAs should not be used to treat acute symptoms.

Pregnancy and lactation

Salmeterol use during pregnancy must be decided based on the risks versus benefits to the mother. There are no well-controlled studies with salmeterol in pregnant women. Some animal studies showed developmental malformation when the mother was given several clinical doses orally. In rats, salmeterol xinafoate is excreted in the milk. However, since there is no data to show excretion of salmeterol in a mother's breast milk, a decision on whether to continue or discontinue therapy should be decided based on the important benefits it provides to the mother. Pregnant and lactating women should consult their doctors before using salmeterol.

Side effects

Due to its vasodilation properties, the common side effects of salmeterol are *

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

, *

sinus infection Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, headac ...

, and *

migraine headaches Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

. Other side effects * muscle tremors, * hypokalemia due to direct effect on beta-2 receptors on skeletal muscle. In most cases, salmeterol side effects are minor and either do not require treatment or can easily be treated. Certain side effects, however, should be reported to a healthcare provider immediately. Some of these more serious side effects include * very fast heart rate, *

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

, and * worsening

breathing problems Shortness of breath (SOB), also medically 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 dis ...

Structure-activity relationship

Salmeterol has an

aryl In organic chemistry, an aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar" is used ...

alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloa ...

group with a chain length of 11 atoms from the amine. This bulkiness makes the compound more lipophilic and it also makes it selective to β₂ adrenergic receptors.

History

Salmeterol, first marketed and manufactured by

Glaxo GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...

(now GlaxoSmithKline, GSK) in the 1980s, was released as Serevent in 1990. The product is marketed by GSK under the Allen & Hanburys brand in the UK. In November 2005, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) released a health advisory, alerting the public to findings that show the use of long-acting β₂ agonists could lead to a worsening of symptoms, and in some cases death. While the use of inhaled LABAs are still recommended in asthma guidelines for the resulting improved symptom control,British Thoracic Society & Scottish Intercollegiate Guidelines Network (SIGN). ''British Guideline on the Management of Asthma''. Guideline No. 63. Edinburgh:SIGN; 2004.
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) further concerns have been raised. A large meta-analysis of pooled results from 19 trials with 33,826 participants, suggests that salmeterol may increase the small risks of asthma-related deaths, and this additional risk is not reduced with the additional use of inhaled steroids (e.g., as with the combination product

fluticasone/salmeterol Fluticasone/salmeterol, sold under the brand name Advair among others, is a fixed-dose combination medication containing fluticasone propionate and salmeterol. It is used in the management of asthma and chronic obstructive pulmonary disease (CO ...

). This seems to occur because although LABAs relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning.

Society and culture

Names

Combinations of inhaled steroids and these long-acting bronchodilators are becoming more widespread; the most common combination currently in use is

(brand names Seretide (UK) and Advair (US)). Another combination is budesonide/formoterol (brand name Symbicort).

References

External links

* {{Portal bar , Medicine Beta2-adrenergic agonists GSK plc brands Phenylethanolamines Withdrawn drugs