Salmeterol
Encyclopedia
Salmeterol is a long-acting beta2-adrenergic receptor agonist
drug
that is currently prescribed for the treatment of asthma
and chronic obstructive pulmonary disease
(COPD). It is currently available as a dry powder inhaler
that releases a powdered form of the drug. Before 2008, it was also available as a metered-dose inhaler (MDI).
and is prescribed concurrently with a corticosteroid, such as beclomethasone. The primary noticeable difference of salmeterol to salbutamol
is that the duration of action lasts approximately 12 hours in comparison with 4–6 hours of salbutamol.
When used regularly every day as prescribed, inhaled salmeterol decreases the number and severity of asthma attacks. However, like all LABA medications, it is not for use for relieving an asthma attack that has already started.
Inhaled salmeterol works like other beta 2-agonists, causing bronchodilation by relaxing the smooth muscle in the airway so as to treat the exacerbation of asthma. The long duration of action occurs by the molecules initially diffusing into the plasma membrane of the lung cells, and then slowly being released back outside the cell where they can come into contact with the beta-2 adrenoceptors, with the long carbon chain forming an anchor in the membrane. Interestingly, salmeterol binding to the beta-adrenoceptor does not induce desensitisation or internalisation of receptors which may also contribute to its long therapeutic duration of action. Formoterol
has been demonstrated to have a faster onset of action than salmeterol as a result of a lower lipophilic
ity, and has also been demonstrated to be more potent—a 12 µg dose of formoterol has been demonstrated to be equivalent to a 50 µg dose of salmeterol.
include salmeterol, formoterol
, bambuterol
, and sustained-release oral salbutamol
. Combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread; the most common combination currently in use is fluticasone/salmeterol
(Advair in the United States, Seretide in the UK).
and arrhythmia.
Salmeterol, marketed and manufactured by GlaxoSmithKline
, in the 1980s and 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
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, further concerns have been raised, by a large meta-analysis of the pooled results from 19 trials with 33,826 participants, that salmeterol may increase the small risks of asthma deaths, and this additional risk is not reduced with the additional use of inhaled steroids (e.g., as with the combination product Fluticasone/salmeterol
).
This seems to occur because although LABAs relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning.
.
Beta2-adrenergic receptor agonist
β2-adrenergic agonists, also known as β2-adrenergic receptor agonists, are a class of drugs used to treat asthma and other pulmonary disease states.-Uses:...
drug
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
that is currently prescribed for the treatment of asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
and chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
(COPD). It is currently available as a dry powder inhaler
Dry powder inhaler
A Dry powder inhaler is a device that delivers medication to the lungs in the form of a dry powder. DPIs are commonly used to treat respiratory diseases such as asthma, bronchitis, emphysema and COPD although DPIs have also been used in the treatment of diabetes mellitus.DPIs are an alternative...
that releases a powdered form of the drug. Before 2008, it was also available as a metered-dose inhaler (MDI).
Structure activity relationship
Salmeterol has an aryl alkyl group with a chain length of 11-atoms from the amine. This bulkiness makes the compound more lipophilic and it also makes it β receptor selective.Indications
It is a long-acting beta-adrenoceptor agonist (LABA), usually prescribed only for severe persistent asthma following previous treatment with a short-acting beta agonist such as salbutamolSalbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
and is prescribed concurrently with a corticosteroid, such as beclomethasone. The primary noticeable difference of salmeterol to salbutamol
Salbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
is that the duration of action lasts approximately 12 hours in comparison with 4–6 hours of salbutamol.
When used regularly every day as prescribed, inhaled salmeterol decreases the number and severity of asthma attacks. However, like all LABA medications, it is not for use for relieving an asthma attack that has already started.
Inhaled salmeterol works like other beta 2-agonists, causing bronchodilation by relaxing the smooth muscle in the airway so as to treat the exacerbation of asthma. The long duration of action occurs by the molecules initially diffusing into the plasma membrane of the lung cells, and then slowly being released back outside the cell where they can come into contact with the beta-2 adrenoceptors, with the long carbon chain forming an anchor in the membrane. Interestingly, salmeterol binding to the beta-adrenoceptor does not induce desensitisation or internalisation of receptors which may also contribute to its long therapeutic duration of action. Formoterol
Formoterol
Formoterol or eformoterol is a long-acting β2-agonist used in the management of asthma and/or chronic obstructive pulmonary disease...
has been demonstrated to have a faster onset of action than salmeterol as a result of a lower lipophilic
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
ity, and has also been demonstrated to be more potent—a 12 µg dose of formoterol has been demonstrated to be equivalent to a 50 µg dose of salmeterol.
Formulations
Currently available long-acting beta2-adrenoceptor agonistsBeta2-adrenergic receptor agonist
β2-adrenergic agonists, also known as β2-adrenergic receptor agonists, are a class of drugs used to treat asthma and other pulmonary disease states.-Uses:...
include salmeterol, formoterol
Formoterol
Formoterol or eformoterol is a long-acting β2-agonist used in the management of asthma and/or chronic obstructive pulmonary disease...
, bambuterol
Bambuterol
Bambuterol is a long acting beta-adrenoceptor agonist used in the treatment of asthma; it also is a prodrug of terbutaline. Commercially, the AstraZeneca pharmaceutical company produces and markets bambuterol as Bambec and Oxeol ....
, and sustained-release oral salbutamol
Salbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
. Combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread; the most common combination currently in use is fluticasone/salmeterol
Fluticasone/salmeterol
The combination preparation fluticasone/salmeterol is a formulation containing fluticasone propionate and salmeterol xinafoate used in the management of asthma and chronic obstructive pulmonary disease...
(Advair in the United States, Seretide in the UK).
Side effects
Side effects include tremorTremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
and arrhythmia.
History and concerns
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
, in the 1980s and 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
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
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, further concerns have been raised, by a large meta-analysis of the pooled results from 19 trials with 33,826 participants, that salmeterol may increase the small risks of asthma 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
The combination preparation fluticasone/salmeterol is a formulation containing fluticasone propionate and salmeterol xinafoate used in the management of asthma and chronic obstructive pulmonary disease...
).
This seems to occur because although LABAs relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning.
Synthesis
Salmeterol can be prepared starting from phenethyl alcoholPhenethyl alcohol
Phenethyl alcohol, or 2-phenylethanol, is the organic compound with the formula C6H5CH2CH2OH. This colourless liquid occurs widely in nature, being found in a variety of essential oils, including rose, carnation, hyacinth, Aleppo pine, orange blossom, ylang-ylang, geranium, neroli, and champaca...
.