Salbutamol

Salbutamol

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Systematic (IUPAC) name
(RS)-4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol
Clinical data
Pregnancy category	AU: A US: C (Risk not ruled out)
Routes of administration	Oral, inhalational, IV
Legal status
Legal status	AU: S3 (Pharmacist only) CA: OTC UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Metabolism	Hepatic
Biological half-life	1.6 hours
Excretion	Renal
Identifiers
CAS Number	18559-94-9
ATC code	R03AC02 (WHO) R03CC02
PubChem	CID 2083
IUPHAR/BPS	558
DrugBank	APRD00553
ChemSpider	1999
Chemical data
Formula	C13H21NO3
Molar mass	239.311[[]]
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Salbutamol (INN) or albuterol (USAN) 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 by GlaxoSmithKline as Ventolin, Aerolin or Ventorlin depending on the market; by Cipla as Asthalin; by Schering-Plough as Proventil and by Teva as ProAir.

Salbutamol was the first selective Β2-receptor agonist to be marketed — in 1968. It was first sold by Allen & Hanburys under the brand name Ventolin. The drug was an instant success, and has been used for the treatment of asthma ever since.

Salbutamol sulfate is usually given by the inhaled route for direct effect on bronchial smooth muscle. This is usually achieved through a metered dose inhaler (MDI), nebulizer or other proprietary delivery devices (e.g. Rotahaler or Autohaler). In these forms of delivery, the maximal effect of Salbutamol can take place within five to twenty minutes of dosing, though some relief is immediately seen. Salbutamol can also be given orally as an inhalant or intravenously.

Clinical use

Salbutamol is specifically indicated in the following conditions:

• Acute asthma
• Symptom relief during maintenance therapy of asthma and other conditions with reversible or irreversible airways obstruction (including COPD and bronchitis)
• Protection against exercise-induced asthma
• Can be aerosolized with a nebulizer for patients with cystic fibrosis, along with ipratropium bromide, acetylcysteine, and pulmozyme.
• Subtypes of congenital myasthenic syndromes associated to mutations in Dok-7.

As a β₂-agonist, salbutamol also finds use in obstetrics. Intravenous salbutamol can be used as a tocolytic to relax the uterine smooth muscle to delay premature labour. While preferred over agents such as atosiban and ritodrine, its role has largely been replaced by the calcium-channel blocker nifedipine which is more effective, better tolerated and orally administered.

In an emergency, EMS providers consider the administration of salbutamol when they see active wheezing, bronchospasm and a past diagnosis of asthma. The drug is most often administered through a nebulizer with 6-8 liters per minute of oxygen. A normal dose is 2.5 mg in 3 mL of respiratory saline.

Side effects / health consequences

The most common side effects are of fine tremor, nervousness, headache, muscle cramps, dry mouth, and palpitation. Other symptoms may be tachycardia (rapid heart rate), arrhythmias, flushing, myocardial ischaemia, and disturbances of sleep and behaviour. Rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasm, urticaria, angioedema, hypotension, and collapse, whilst high doses may cause hypokalaemia (low potassium levels), especially in patients with renal failure and those on certain diuretics and xanthine derivaties.

File:Ventolin 2mg.JPG

Ventolin 2mg tablets made by GSK (Turkey)

Diet and bodybuilding use

Salbutamol is taken by some as an alternative to clenbuterol for purposes of fat burning, and/or as a performance enhancer. Abuse of the drug may be confirmed by detection of its presence in plasma or urine, typically in the 10-50o0 µg/L range.

Doping

Clinical studies show no compelling evidence that salbutamol and other beta 2 agonists can increase performance in healthy athletes. In spite of this, salbutamol remains on WADAs prohibited list and many athletes have been banned for use of salbutamol.

According to two small and limited studies, performed on 8 and 16 subjects respectively, salbutamol increases the performance even for a person without asthma.

Detection of use

Salbutamol may be quantified in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients or to aid in a medicolegal death investigation. Urinary salbutamol concentrations are frequently measured in competitive sports programs, for which a level in excess of 1000 μg/L is considered to represent abuse. The window of detection for urine testing is on the order of just 24 hours, given the relatively short elimination half-life of the drug.

Ban of CFC-containing inhalers

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The components of a salbutamol inhaler

The U.S. Food and Drug Administration (FDA) in April 2005 mandated that all (including salbutamol) inhalers containing chlorofluorocarbons (CFCs) will be prohibited in the United States as of December 31, 2008. CFC inhalers had previously been given "essential use" status, exempting it from a CFC-production ban, however in accordance with the Montreal Protocol they will be phased out; in many other countries patients have been transitioned to non-CFC based inhalers using hydrofluoroalkane (HFA) propellant. Pharmaceutical manufacturers are expected to produce adequate supplies of alternative (HFA) inhalers by 2009.

One drawback of this transition to HFA inhalers is that, due to patent restrictions, all HFA salbutamol inhalers are "brand-name" (ProAir, Proventil, and Ventolin). They cost approximately $20 more per inhaler than existing generic CFC salbutamol inhalers. These new formulations are patented. An industry consortium was formed to spread the costs of the FDA safety studies to get propellants such as 134a and 227 approved.

Generic HFA salbutamol inhalers are not expected to reach the United States market until after 2012 due to existing patents.

Salbutamol is widely used, and accounts for anywhere from 78% of all bronchodilator prescriptions in 2005 to 85% in 2008. However, patients in the United States who cannot tolerate the HFA salbutamol inhalers will not have a single salbutamol alternative available to them domestically after December 31, 2008. The FDA did not approve any alternatives to HFA and there are few standard inhaled lung medications in the United States that come in Dry Powder Inhaler (DPI) versions. Noticeably missing is salbutamol in DPI form in the United States, although it is available in most of the rest of the world in salbutamol DPIs.

Synthesis

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Collin, D. T.; Hartely, D.; Jack, D.; Lunts, L. H. C.; Press, J. C.; Ritchie, A. C.; Toon, P.; J. Med. Chem. 1970, 13, 674.

http://dx.doi.org/10.1021/jm00298a022

See also

• Epinephrine
• Beclometasone dipropionate
• Ipratropium

References

Additional notes

6. S

External links

• Volmax Drug Information
• Side Effects
• U.S. National Library of Medicine: Drug Information Portal - Albuterol

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