Common side effects include shakiness, headache, fast heart rate, dizziness, and feeling anxious.[6] Serious side effects may include worsening bronchospasm, irregular heartbeat, and low blood potassium levels.[6] It can be used during pregnancy and breastfeeding, but safety is not entirely clear.[6][9] It is a short-acting β2 adrenergic receptor agonist which works by causing relaxation of airway smooth muscle.[6] Salbutamol was patented in 1966 in Britain and became commercially available in the UK in 1969.[10][11] It was approved for medical use in the United States in 1982.[6] It is on the World Health Organization's List of Essential Medicines, which lists the most effective and safe medicines needed in a health system.[12] Salbutamol is available as a generic medication.[6] The wholesale cost in the developing world of an inhaler which contains 200 doses is between US$1.12 and US$2.64 as of 2014.[13] In the United States, it is between US$25 and US$50 for a typical month's supply.[14] In 2016, it was the 10th most prescribed medication in the United States, with more than 47 million prescriptions.[15]
Medical usesEdit
Salbutamol is typically used to treat bronchospasm (due to any cause—allergic asthma or exercise-induced), as well as chronic obstructive pulmonary disease.[6] It is also one of the most common medicines used in rescue inhalers (short-term bronchodilators to alleviate asthma attacks).[16]
As a β2 agonist, salbutamol also has 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 While preferred over agents such as atosiban and ritodrine, its role has largely been replaced by the calcium channel blocker nifedipine, which is more effective and better tolerated.[17]
Salbutamol has been used to treat acute hyperkalemia, as it stimulates potassium flow into cells, thus lowering the potassium in the blood.[7]
Adverse effectsEdit
The most common side effects are fine tremor, anxiety, headache, muscle cramps, dry mouth, and palpitation.[18] Other symptoms may include tachycardia, arrhythmia, flushing of the skin, myocardial ischemia (rare), and disturbances of sleep and behaviour.[18] Rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasms, urticaria (hives), angioedema, hypotension, and collapse. High doses or prolonged use may cause hypokalemia, which is of concern especially in patients with renal failure and those on certain diuretics and xanthine derivatives.[18]
PharmacologyEdit
The tertiary butyl group in salbutamol makes it more selective for β2 receptors,[19] which are the predominant receptors on the bronchial smooth muscles. Activation of these receptors causes adenylyl cyclase to convert ATP to cAMP, beginning the signalling cascade that ends with the inhibition of myosin phosphorylation and lowering the intracellular concentration of calcium ions (myosin phosphorylation and calcium ions are necessary for muscle contractions). The increase in cAMP also inhibits inflammatory cells in the airway, such as basophils, eosinophils, and most especially mast cells, from releasing inflammatory mediators and cytokines.[20][21] Salbutamol and other β2 receptor agonists also increase the conductance of channels sensitive to calcium and potassium ions, leading to hyperpolarization and relaxation of bronchial smooth muscles.[22]
Salbutamol is either filtered out by the kidneys directly or is first metabolized into 4'-O-sulfate, which is excreted in the urine.[8]
ChemistryEdit
Structure and activityEdit

(R)-(−)-salbutamol (top) and (S)-(+)-salbutamol (bottom)
Salbutamol is sold as a racemic mixture. The (R)-(−)-enantiomer (CIP nomenclature) is shown in the image at right (top), and is responsible for the pharmacologic activity; the (S)-(+)-enantiomer (bottom) blocks metabolic pathways associated with elimination of itself and of the pharmacologically active enantiomer (R).[23] The slower metabolism of the (S)-(+)-enantiomer also causes it to accumulate in the lungs, which can cause airway hyperreactivity and inflammation.[24]
HistoryEdit
Salbutamol was discovered in 1966 by a team led by David Jack at the Allen and Hanburys laboratory (a subsidiary of Glaxo) in Ware, Hertfordshire, England, and was launched as Ventolin in 1969.[25]
The 1972 Munich Olympics were the first Olympics where anti-doping measures were deployed, and at that time beta-2 agonists were considered to be stimulants with high risk of abuse for doping. Inhaled salbutamol was banned from those games, but by 1986 was permitted (although oral beta-2 agonists were not). After a steep rise in the number of athletes taking beta-2 agonists for asthma in the 1990s, Olympic athletes were required to provide proof that they had asthma in order be allowed to use inhaled beta-2 agonists.[26]
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