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Salbutamol - Albuterol Side Effects

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Salbutamol, also known as albuterol and marketed as Ventolin among other names, is a medication that opens up the medium and large airways in the lungs. It is used to treat asthma including asthma attacks, exercise-induced bronchoconstriction, and chronic obstructive pulmonary disease (COPD). It may also be used to treat high blood potassium levels. Salbutamol is usually used with an inhaler or nebulizer but is also available as a pill and intravenous solution. Onset of action of the inhaled version is typically within 15 minutes and lasts for two to six hours.

Common side effects include shakiness, headache, fast heart rate, dizziness, and feeling anxious. Serious side effects may include worsening bronchospasm, irregular heartbeat, and low blood potassium levels. It can be used during pregnancy and breastfeeding, but safety is not entirely clear. It is a short-acting ?2 adrenergic receptor agonist which works by causing airway smooth muscles to relax.

Salbutamol was first made in 1967 in Britain and became commercially available in the UK in 1969. It was approved for medical use in the United States in 1982. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world of an inhaler which contains 200 doses is between $1.12 and $2.64 (USD) as of 2014. In the United States, it is between $25 and $50 for a typical month supply.


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Medical uses

Salbutamol is typically used to treat bronchospasm (due to any cause - allergic asthma or exercise-induced), as well as chronic obstructive pulmonary disease. It is also one of the most common medicines used in rescue inhalers (short-term bronchodilators to alleviate asthma attacks).

As a ?2 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 While preferred over agents such as atosiban and ritodrine, its role has largely been replaced by the calcium channel blocker nifedipine, which is more effective, better tolerated, and administered orally.

Salbutamol has been used to treat acute hyperkalemia, as it stimulates potassium flow into cells, thus lowering the level in the blood.


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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 of the skin, myocardial ischemia (rare), and disturbances of sleep and behaviour. Rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasms, urticaria (hives), 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.


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Pharmacology

The tertiary butyl group in salbutamol makes it more selective for ?2 receptors, 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. Salbutamol and other ?2 receptor agonists also increase the conductance of channels sensitive to calcium and potassium ions, leading to hyperpolarization and relaxation of bronchial smooth muscles.

Salbutamol is either filtered out by the kidneys directly or is first metabolized into 4'-O-sulphate, which is excreted in the urine.


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Chemistry

Structure and activity

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). The slower metabolism of the (S)-(+)-enantiomer also causes it to accumulate in the lungs, which can cause airway hyperreactivity and inflammation.


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History

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.


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Society and culture

Cost

The wholesale cost of a 200-dose inhaler is between $1.12 and $2.64 (USD) in the developing world as of 2014 and GB£1.50 in the United Kingdom as of 2015. In the United States, a typical month supply is between $25 and $50.

Names

Salbutamol is the INN (international nonproprietary name) while albuterol is the USAN (United States adopted name). The drug is usually manufactured and distributed as the sulphate salt (salbutamol sulphate).

It was first sold by Allen & Hanburys (UK) under the brand name Ventolin, and has been used for the treatment of asthma ever since. The drug is marketed under many names worldwide.

Doping

There is no compelling evidence that salbutamol and other ?2 agonists can increase performance in healthy athletes. 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."

According to two small and limited studies, salbutamol increases performance on endurance exercise even for a person without asthma.

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.

Salbutamol has been shown to improve muscle weight in rats 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. Abuse of the drug may be confirmed by detection of its presence in plasma or urine, typically exceeding 1000 µg/L. 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, estimated at between 5 and 6 hours following oral administration of 4 mg.


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Research

Salbutamol has been studied in subtypes of congenital myasthenic syndrome associated with mutations in Dok-7.

It has also been tested in a trial aimed at treatment of spinal muscular atrophy; it is speculated to modulate the alternative splicing of the SMN2 gene, increasing the amount of the SMN protein whose deficiency is regarded as a cause of the disease.


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Veterinary use

Salbutamol's low toxicity makes it safe for other animals and thus is the medication of choice for treating acute airway obstruction in most species. It is usually used to treat bronchospasm or coughs in cats and dogs and used as a bronchodilator in horses with recurrent airway obstruction; it can also be used in emergencies to treat asthmatic cats.

Toxic effects require an extremely high dose, and most overdoses are due to dogs chewing on and puncturing an inhaler or nebulizer vial.

Source of the article : Wikipedia



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