Salbutamol

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 as Ventolin among other brand names.

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. It can also be given orally as an inhalant or intravenously.

Medical uses
Salbutamol is typically used to treat bronchospasm (due to either asthma or exercise) as well as chronic obstructive pulmonary disease.

Other uses include in cystic fibrosis, along with ipratropium bromide, acetylcysteine, and pulmozyme and 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 labor. While preferred over agents such as atosiban and ritodrine, its role has largely been replaced by the calcium-channel blocker nifedipine, which is more effective, better tolerated and orally administered.

Adverse effects
The most common side effects are fine tremor, anxiety, headache, muscle cramps, dry mouth, and palpitation. Other symptoms may include tachycardia, arrhythmia, flushing, myocardial ischemia, and disturbances of sleep and behaviour. Rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasm, urticaria, angioedema, hypotension, and collapse. High doses may cause hypokalaemia which are of concern in patients with renal failure and those on certain diuretics and xanthine derivatives.

Structure activity relationship
The tertiary butyl group in salbutamol (or albuterol) makes it more selective for β2-receptors. The drug is sold as a racemic mixture mainly because the S isomer blocks metabolism pathways while the R isomer shows activity.

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 10-500 µg/L range.

Doping
Clinical studies show no compelling evidence that salbutamol and other β2-agonists can increase performance in healthy athletes. In spite of this, salbutamol requires "a declaration of Use in accordance with the International Standard for Therapeutic Use Exemptions" under the current WADA prohibited list.

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 forensic 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


The U.S. Food and Drug Administration (FDA) in April 2005 mandated all (including salbutamol) inhalers containing chlorofluorocarbons (CFCs) were to 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 were expected to produce adequate supplies of alternative (HFA) inhalers by 2009.

Due to patent restrictions, HFA salbutamol inhalers cost significantly more per inhaler than existing generic CFC salbutamol inhalers. 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.

Brand names
It is marketed by GlaxoSmithKline as Ventolin, Ventoline, Ventilan, Aerolin or Ventorlin, depending on the market; by Cipla as Asthalin and Asthavent; by Schering-Plough as Proventil and by Teva as ProAir.

Additional notes

 * S
 * S
 * S
 * S
 * S
 * S