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.[2] 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 (UK) under the brand name Ventolin, and has been used for the treatment of asthma ever since.[3] It was approved for use in the US by the Food and Drug Administration (FDA) in May 1982.[4]
Salbutamol sulfate is sold in the USA as Ventolin HFA,[5] ProAir HFA,[6] or Proventil HFA,[7] and is also available in extended release tablets.[8] It 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 20 minutes of dosing, though some relief is immediately seen. Mean duration of effect is roughly 2 hours.[9] It can also be given intravenously.[10]
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[11] Compliance with the Montreal Protocol, which requires the banning of the use of ozone-layer depleting CFCs, has caused the cost of inhalers, however, to increase as much as ten-fold as generics were forced off the market from 2009 to 2013 by new patents obtained by pharmaceutical companies for non-CFC delivery systems.
Medical uses[edit]
Salbutamol is typically used to treat bronchospasm (due to any cause, allergen asthma or exercise-induced), as well as chronic obstructive pulmonary disease.[12] Emergency medical practice commonly treats people presenting with asthma who report taking their salbutamol inhaler as prescribed with salbutamol. In general, people tolerate large doses well.
Other uses include in cystic fibrosis and subtypes of congenital myasthenic syndromes associated to mutations in Dok-7.[citation needed]
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 While preferred over agents such as atosiban and ritodrine, its role has largely been replaced by the calcium-channel blocker nifedipine, which is more effective, better tolerated and orally administered.[13]
Salbutamol is used to treat acute hyperkalemia as it stimulates potassium to flow in cells thus lowering the level in the blood.[14][15]
Salbutamol has also been trialled in spinal muscular atrophy where it appears to show modest benefits. The drug is speculated to modulate the alternative splicing of the SMN2 gene, increasing the amount of the SMN protein whose deficiency is regarded as the root cause of the disease.[16][17]
Adverse effects[edit]
The most common side effects are fine tremor, anxiety, headache, muscle cramps, dry mouth, and palpitation.[18] Other symptoms may include tachycardia, arrhythmia, flushing, myocardial ischemia (rare), and disturbances of sleep and behaviour.[18] Rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasm, urticaria, angioedema, hypotension, and collapse. High doses or prolonged use may cause hypokalaemia, which is of concern especially in patients with renal failure and those on certain diuretics and xanthine derivatives.[18]
Ventolin 2mg tablets made by GSK (Turkey)
Chemistry[edit]
(R)-Salbutamol (top) and (S)-salbutamol
Structure-activity relationships[edit]
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)-enantiomer blocks metabolism pathways while the (R)-enantiomer shows activity.[19]
Society and culture[edit]
Bodybuilding[edit]
Salbutamol has been shown to improve muscle weight in rats [20] and anecdotal reports hypothesise that it might be an alternative to clenbuterol for purposes of fat burning and muscle gain, with multiple studies supporting this claim.[21][22][23][24][25] Abuse of the drug may be confirmed by detection of its presence in plasma or urine, typically exceeding 1000 µg/L.[26]
Doping[edit]
Clinical studies show no compelling evidence that salbutamol and other β2-agonists can increase performance in healthy athletes.[27] In spite of this, salbutamol required "a declaration of Use in accordance with the International Standard for Therapeutic Use Exemptions" under the 2010 WADA prohibited list. This requirement was relaxed when the 2011 list was published to permit the use of "salbutamol (maximum 1600 micrograms over 24 hours) and salmeterol when taken by inhalation in accordance with the manufacturers’ recommended therapeutic regimen." [28][29]
According to two small and limited studies, performed on eight and 16 subjects, respectively, salbutamol increases the performance even for a person without asthma.[30][31][32]
Another study contradicts the above findings, however. The double blind, randomised test conducted on 12 non-asthmatic athletes concluded that salbutamol had a negligible effect on endurance performance. Nevertheless, the study also showed that the drug's bronchodilating effect may have improved respiratory adaptation at the beginning of exercise.[33]
Detection of use[edit]
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[26][34][35] (estimated at between 5 and 6 hours following oral administration of 4 mg[36]).
Brand names[edit]
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, by Teva as ProAir and Novo-Salbutamol HFA (Canada), Salamol or Airomir, by Beximco (Bangladesh) as AZMASOL by Ad-din Pharma as Ventosol and by Alphapharm as Asmol.
Salbutamol was the first selective β2-receptor agonist to be marketed in 1968. It was first sold by Allen & Hanburys (UK) under the brand name Ventolin, and has been used for the treatment of asthma ever since.[3] It was approved for use in the US by the Food and Drug Administration (FDA) in May 1982.[4]
Salbutamol sulfate is sold in the USA as Ventolin HFA,[5] ProAir HFA,[6] or Proventil HFA,[7] and is also available in extended release tablets.[8] It 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 20 minutes of dosing, though some relief is immediately seen. Mean duration of effect is roughly 2 hours.[9] It can also be given intravenously.[10]
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[11] Compliance with the Montreal Protocol, which requires the banning of the use of ozone-layer depleting CFCs, has caused the cost of inhalers, however, to increase as much as ten-fold as generics were forced off the market from 2009 to 2013 by new patents obtained by pharmaceutical companies for non-CFC delivery systems.
Medical uses[edit]
Salbutamol is typically used to treat bronchospasm (due to any cause, allergen asthma or exercise-induced), as well as chronic obstructive pulmonary disease.[12] Emergency medical practice commonly treats people presenting with asthma who report taking their salbutamol inhaler as prescribed with salbutamol. In general, people tolerate large doses well.
Other uses include in cystic fibrosis and subtypes of congenital myasthenic syndromes associated to mutations in Dok-7.[citation needed]
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.[13]
Salbutamol is used to treat acute hyperkalemia as it stimulates potassium to flow in cells thus lowering the level in the blood.[14][15]
Salbutamol has also been trialled in spinal muscular atrophy where it appears to show modest benefits. The drug is speculated to modulate the alternative splicing of the SMN2 gene, increasing the amount of the SMN protein whose deficiency is regarded as the root cause of the disease.[16][17]
Adverse effects[edit]
The most common side effects are fine tremor, anxiety, headache, muscle cramps, dry mouth, and palpitation.[18] Other symptoms may include tachycardia, arrhythmia, flushing, myocardial ischemia (rare), and disturbances of sleep and behaviour.[18] Rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasm, urticaria, angioedema, hypotension, and collapse. High doses or prolonged use may cause hypokalaemia, which is of concern especially in patients with renal failure and those on certain diuretics and xanthine derivatives.[18]
Ventolin 2mg tablets made by GSK (Turkey)
Chemistry[edit]
(R)-Salbutamol (top) and (S)-salbutamol
Structure-activity relationships[edit]
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)-enantiomer blocks metabolism pathways while the (R)-enantiomer shows activity.[19]
Society and culture[edit]
Bodybuilding[edit]
Salbutamol has been shown to improve muscle weight in rats [20] and anecdotal reports hypothesise that it might be an alternative to clenbuterol for purposes of fat burning and muscle gain, with multiple studies supporting this claim.[21][22][23][24][25] Abuse of the drug may be confirmed by detection of its presence in plasma or urine, typically exceeding 1000 µg/L.[26]
Doping[edit]
Clinical studies show no compelling evidence that salbutamol and other β2-agonists can increase performance in healthy athletes.[27] In spite of this, salbutamol required "a declaration of Use in accordance with the International Standard for Therapeutic Use Exemptions" under the 2010 WADA prohibited list. This requirement was relaxed when the 2011 list was published to permit the use of "salbutamol (maximum 1600 micrograms over 24 hours) and salmeterol when taken by inhalation in accordance with the manufacturers’ recommended therapeutic regimen." [28][29]
According to two small and limited studies, performed on eight and 16 subjects, respectively, salbutamol increases the performance even for a person without asthma.[30][31][32]
Another study contradicts the above findings, however. The double blind, randomised test conducted on 12 non-asthmatic athletes concluded that salbutamol had a negligible effect on endurance performance. Nevertheless, the study also showed that the drug's bronchodilating effect may have improved respiratory adaptation at the beginning of exercise.[33]
Detection of use[edit]
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[26][34][35] (estimated at between 5 and 6 hours following oral administration of 4 mg[36]).
Brand names[edit]
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, by Teva as ProAir and Novo-Salbutamol HFA (Canada), Salamol or Airomir, by Beximco (Bangladesh) as AZMASOL by Ad-din Pharma as Ventosol and by Alphapharm as Asmol.
No comments:
Post a Comment