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{{Drugbox | Verifiedfields = changed | verifiedrevid = 464386379 | IUPAC_name = (RS)-2-(hydroxymethyl)-4-{1-hydroxy-2-[6-(4-phenylbutoxy) hexylamino]ethyl}phenol | image = Structure of Salmeterol.png | width = 200 | imagename = 1 : 1 mixture (racemate) | drug_name = Salmeterol

| tradename = Serevent | Drugs.com = Monograph | pregnancy_category = C | legal_AU = S4 | legal_CA = | legal_UK = POM | legal_US = Rx-only | legal_status = | routes_of_administration = oral Inhalation

| bioavailability = | protein_bound = 96% | metabolism = hepatic CYP3A4 | elimination_half-life = 5.5 h | excretion =

| CASNo_Ref =  checkY | CAS_number_Ref =  checkY | CAS_number = 89365-50-4 | ATC_prefix = R03 | ATC_suffix = AC12 | PubChem = 5152 | IUPHAR_ligand = 559 | DrugBank_Ref =  checkY 

| DrugBank = DB00938

| ChemSpiderID_Ref =  checkY | ChemSpiderID = 7987886 | UNII_Ref =  checkY | UNII = 2I4BC502BT | KEGG_Ref =  checkY | KEGG = D05792 | ChEBI_Ref =  checkY | ChEBI = 9011 | ChEMBL_Ref =  checkY | ChEMBL = 1263

| C=25 | H=37 | N=1 | O=4 | molecular_weight = 415.57 | smiles = OCc1cc(ccc1O)[C@H](O)CNCCCCCCOCCCCc2ccccc2 | InChI = 1/C25H37NO4/c27-20-23-18-22(13-14-24(23)28)25(29)19-26-15-7-1-2-8-16-30-17-9-6-12-21-10-4-3-5-11-21/h3-5,10-11,13-14,18,25-29H,1-2,6-9,12,15-17,19-20H2/t25-/m1/s1 | InChIKey = GIIZNNXWQWCKIB-RUZDIDTEBA | StdInChI_Ref =  checkY | StdInChI = 1S/C25H37NO4/c27-20-23-18-22(13-14-24(23)28)25(29)19-26-15-7-1-2-8-16-30-17-9-6-12-21-10-4-3-5-11-21/h3-5,10-11,13-14,18,25-29H,1-2,6-9,12,15-17,19-20H2/t25-/m1/s1 | StdInChIKey_Ref =  checkY | StdInChIKey = GIIZNNXWQWCKIB-RUZDIDTESA-N }}

Salmeterol is a long-acting beta2-adrenergic receptor agonist drug used in the maintenance and prevention of asthma symptoms and maintenance of chronic obstructive pulmonary disease (COPD) symptoms.[1] Symptoms include shortness of breath, wheezing, coughing and chest tightness. Also, it used to prevent breathing difficulties during exercise (exercise induced bronchospasm).[2]. It is marketed as Serevent in the US.[3] It is available as a dry powder inhaler that releases a powdered form of the drug. It was previously available as a metered-dose inhaler (MDI) but was discontinued in the US in 2002.[1],[4] It is still available as a MDI in the UK as of 2013.

Structure activity relationship

[edit]

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 beta2-adrenergic receptor selective.[5]

Indications

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Salmeterol is a long-acting beta2-adrenoceptor agonist (LABA), used in moderate to severe persistent asthma following previous treatment with a short-acting beta2-adrenoceptor agonist (SABA) such as salbutamol (albuterol). LABAs should not be used as a mono-therapy, instead, they should be used concurrently with a corticosteroid, such as beclometasone dipropionate or fluticasone propionate in the treatment of asthma to minimize serious reactions such as asthma related deaths. In chronic obstructive pulmonary disease (COPD), LABAs may be used as mono-therapy or in combination with corticosteroids. In exercise induced bronchospasm mono-therapy may be indicated in patients without persistent asthma. LABAs should not be used to treat acute symptoms.[6], [1], [7], Cite error: The <ref> tag has too many names (see the help page)., [2]

The primary noticeable difference of salmeterol from salbutamol, and other short-acting beta2-adrenoceptor agonists (SABAs), is its duration of action. Salmeterol lasts approximately 12 hours in comparison with the salbutamol, which last about 4–6 hours.[6], [1]

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 in 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 beta2 adrenoceptors, with the long carbon chain forming an anchor in the membrane. Interestingly, salmeterol binding to the beta2-adrenoceptor does not induce desensitisation or internalization 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 lipophilicity, 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.[8], [2]

Pregnancy/Lactation

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The FDA assigns a Category C to Salmeterol in pregnancy. Salmeterol use during pregnancy must be decided based on the risks versus benefits to the mother. There are no well-controlled studies with salmeterol diskus 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 are 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 diskus.[9]

Long-acting beta2-adrenoceptor agonists (LABAs)

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Currently available long-acting beta2-adrenoceptor agonists include salmeterol (inhaled or sustained-release oral), formoterol, and bambuterol. Combinations of inhaled steroids and these long-acting bronchodilators are becoming more widespread; the most common combination currently in use is fluticasone/salmeterol (brand names Seretide in the UK and Advair in the United States).

Side effects

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Due to its vasodilation properties, the common side effects of salmeterol are dizziness, sinus infection, and migraine headaches. In most cases, salmeterol side effects are minor and either don't 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 a very fast heart rate, high blood pressure, and worsening breathing problems.[10]

History and concerns

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Salmeterol, first marketed and manufactured by Glaxo in the 1980s, was released as Serevent in 1990.[4] 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 beta2-agonists could lead to a worsening of symptoms, and in some cases death.[11]

While the use of inhaled LABAs are still recommended in asthma guidelines for the resulting improved symptom control,[12] further concerns have been raised. A large meta-analysis of the pooled results from 19 trials with 33,826 participants, suggests 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).[13] This seems to occur because although LABAs relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning.[14]

Synthesis

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Salmeterol can be prepared starting from phenethyl alcohol.[15]

Footnotes

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  1. ^ a b c d "global initiative for chronic obstructive disease" (PDF). goldcopd.org. Retrieved 30 October 2014.
  2. ^ a b c "National Asthma Education and Prevention Program". Retrieved 30 October 2014.
  3. ^ "Salmeterol inhalation index". Retrieved 30 October 2014.
  4. ^ a b "FDA" (PDF). fda.gov.
  5. ^ Medicinal Chemistry of Adrenergics and Cholinergics
  6. ^ a b "global initiative for astma" (PDF). ginasthma.org. Retrieved 30 October 2014.
  7. ^ "Use of long-acting beta agonist in chronic obstructive pulmonary disease". http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087967. Retrieved 30 October 2014. {{cite web}}: External link in |website= (help)
  8. ^ "Recommended Medication for Asthma" (PDF). www.partnershiphp.org.
  9. ^ "Serevent Diskus" (PDF). http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020692s028lbl.pdf. Retrieved 3 November 2014. {{cite web}}: External link in |website= (help)
  10. ^ "Medtv". HealthSavy. Retrieved 8 March 2012.
  11. ^ Advair Diskus, Advair HFA, Brovana, Foradil, Perforomist, Serevent Diskus, and Symbicort Information (Long Acting Beta Agonists) "fda". Retrieved 30 October 2014. {{cite web}}: Check |url= value (help)
  12. ^ British Thoracic Society & Scottish Intercollegiate Guidelines Network (SIGN). British Guideline on the Management of Asthma. Guideline No. 63. Edinburgh:SIGN; 2004. (HTML, Full PDF, Summary PDF)
  13. ^ Salpeter S, Buckley N, Ormiston T, Salpeter E (2006). "Meta-analysis: effect of long-acting beta agonists on severe asthma exacerbations and asthma-related deaths". Ann Intern Med. 144 (12): 904–12. doi:10.7326/0003-4819-144-12-200606200-00126. PMID 16754916. S2CID 30648411.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Krishna Ramanujan (June 9, 2006). "Common asthma inhalers cause up to 80 percent of asthma-related deaths, Cornell and Stanford researchers assert". ChronicalOnline - Cornell University.
  15. ^ Skidmore, I. F.; Lunts, L. H. C.; Finch, H.; Naylor, A.; German Offen., 1984, 3414752; Chem. Abstr., 1986, 102, 95383.


Category:Beta-adrenergic agonists Category:Phenethylamines

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