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Salbutamol

Salbutamol

Overview
Salbutamol or albuterol (USAN
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...

) is a short-acting β2-adrenergic receptor agonist
Beta2-adrenergic receptor agonist
β2-adrenergic agonists, also known as β2-adrenergic receptor agonists, are a class of drugs used to treat asthma and other pulmonary disease states.-Uses:...

 used for the relief of bronchospasm
Bronchospasm
Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...

 in conditions such as asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

 and chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

. It is marketed as Ventolin among other brand names.
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Encyclopedia
Salbutamol or albuterol (USAN
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...

) is a short-acting β2-adrenergic receptor agonist
Beta2-adrenergic receptor agonist
β2-adrenergic agonists, also known as β2-adrenergic receptor agonists, are a class of drugs used to treat asthma and other pulmonary disease states.-Uses:...

 used for the relief of bronchospasm
Bronchospasm
Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...

 in conditions such as asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

 and chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

. 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
Allen & Hanburys
Allen and Hanburys Ltd was a British pharmaceutical manufacturer, absorbed by Glaxo Laboratories in 1958.-History:The business was founded in 1715 in Old Plough Court, Lombard Street, London, by Silvanus Bevan, a Welshman, apothecary and a Quaker...

 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
Metered dose inhaler
A metered-dose inhaler is a device that delivers a specific amount of medication to the airway and lungs, in the form of a short burst of aerosolized medicine that is inhaled by the patient. It is the most commonly used delivery system for treating asthma, chronic obstructive pulmonary disease ...

 (MDI), nebulizer
Nebulizer
In medicine, a nebulizer is a device used to administer medication in the form of a mist inhaled into the lungs....

 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
Inhalant
Inhalants are a broad range of drugs whose volatile vapors are taken in via the nose and trachea. They are taken by volatilization, and do not include drugs that are inhaled after burning or heating...

 or intravenously.

Medical uses


Salbutamol is typically used to treat bronchospasm
Bronchospasm
Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...

 (due to either asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

 or exercise) as well as chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

.

Other uses include in cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...

, along with ipratropium bromide
Ipratropium
Ipratropium bromide is an anticholinergic drug used for the treatment of chronic obstructive pulmonary disease and acute asthma. It blocks the muscarinic acetylcholine receptors in the smooth muscles of the bronchi in the lungs, opening the bronchi...

, acetylcysteine, and pulmozyme and subtypes of congenital myasthenic syndrome
Congenital myasthenic syndrome
Congenital myasthenic syndrome is an inherited neuromuscular disorder caused by defects of several types at the neuromuscular junction...

s associated to mutations in Dok-7
Dok-7
Dok-7 is a non-catalytic cytoplasmic adaptor protein that is expressed specifically in muscle and is essential for the formation of neuromuscular synapses. Further, Dok-7 contains pleckstrin homology and phosphotyrosine-binding domains that are critical for Dok-7 function...

.

As a β2-agonist, salbutamol also finds use in obstetrics
Obstetrics
Obstetrics is the medical specialty dealing with the care of all women's reproductive tracts and their children during pregnancy , childbirth and the postnatal period...

. Intravenous salbutamol can be used as a tocolytic to relax the uterine
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...

 smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

 to delay premature labor. While preferred over agents such as atosiban
Atosiban
Atosiban is an inhibitor of the hormones oxytocin and vasopressin. It is used as an intravenous medication as a labour repressant to halt premature labor. Although initial studies suggested it could be used as a nasal spray and hence would not require hospital admission, it is not used in that form...

 and ritodrine
Ritodrine
Ritodrine is a tocolytic drug, was used to stop premature labor. It is available in oral tablets or as an injection, and is typically used as the hydrochloride salt, ritodrine hydrochloride...

, its role has largely been replaced by the calcium-channel blocker nifedipine
Nifedipine
Nifedipine is a dihydropyridine calcium channel blocker...

, which is more effective, better tolerated and orally administered.

Adverse effects


The most common side effects are fine tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...

, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

, muscle cramps, dry mouth, and palpitation
Palpitation
A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...

. Other symptoms may include tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, arrhythmia, flushing
Flushing (physiology)
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...

, myocardial ischemia
Myocardial ischemia
Myocardial ischemia is an imbalance between myocardial oxygen supply and demand. Left untreated, it results in angina pectoris, myocardial stunning, myocardial hibernation, ischemic preconditioning, postconditioning, or under the most severe instances, acute coronary syndrome and myocardial...

, and disturbances of sleep and behaviour. Rarely occurring, but of importance, are allergic reactions of paradoxical bronchospasm
Bronchospasm
Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...

, urticaria
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...

, angioedema
Angioedema
Angioedema or Quincke's edema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis...

, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

, and collapse
Collapse (medical)
Collapse is a sudden and often unannounced loss of postural tone , often but not necessarily accompanied by loss of consciousness.If the episode was accompanied by a loss of consciousness, the term syncope is used. The main causes are cardiac , seizures or a psychological cause...

. High doses may cause hypokalaemia which are of concern in patients with renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...

 and those on certain diuretics and xanthine
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....

 derivatives.

Diet and bodybuilding use


Salbutamol is taken by some as an alternative to clenbuterol
Clenbuterol
Clenbuterol is a sympathomimetic amine used by sufferers of breathing disorders as a decongestant and bronchodilator. People with chronic breathing disorders such as asthma use this as a bronchodilator to make breathing easier...

 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
World Anti-Doping Agency
The World Anti-Doping Agency , , is an independent foundation created through a collective initiative led by the International Olympic Committee . It was set up on November 10, 1999 in Lausanne, Switzerland, as a result of what was called the "Declaration of Lausanne", to promote, coordinate and...

 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
Montreal Protocol
The Montreal Protocol on Substances That Deplete the Ozone Layer is an international treaty designed to protect the ozone layer by phasing out the production of numerous substances believed to be responsible for ozone depletion...

, 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.

Chemistry



Structure-activity relationships


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.

Synthesis


Salbutamol can be prepared from an acetophenone derivative.

Brand names


It is marketed by GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...

 as Ventolin, Ventoline, Ventilan, Aerolin or Ventorlin, depending on the market; by Cipla
Cipla
Cipla Limited is a prominent Indian pharmaceutical company, best-known outside its home country for manufacturing low-cost anti-AIDS drugs for HIV-positive patients in developing countries...

 as Asthalin and Asthavent; by Schering-Plough
Schering-Plough
Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co...

 as Proventil, by Teva
Teva Pharmaceutical Industries
Teva Pharmaceutical Industries Ltd. , is an international pharmaceutical company headquartered in Petah Tikva, Israel. It specializes in generic and proprietary pharmaceuticals and active pharmaceutical ingredients...

 as ProAir and by Ad-din Pharma as Ventosol

See also

  • Epinephrine
    Epinephrine
    Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

  • Beclometasone dipropionate
    Beclometasone dipropionate
    Beclometasone dipropionate or beclomethasone dipropionate , also referred to as beclometasone , is a potent glucocorticoid steroid. In the form of an inhaler , a wide number of brands of which are available, it is used for the prophylaxis of asthma. As a nasal spray Beclometasone dipropionate (INN...

  • Ipratropium
    Ipratropium
    Ipratropium bromide is an anticholinergic drug used for the treatment of chronic obstructive pulmonary disease and acute asthma. It blocks the muscarinic acetylcholine receptors in the smooth muscles of the bronchi in the lungs, opening the bronchi...

  • Ipratropium/salbutamol
    Ipratropium/salbutamol
    The combination preparation ipratropium bromide/salbutamol is a formulation containing ipratropium bromide and salbutamol sulfate used in the management of chronic obstructive pulmonary disease and asthma...

  • Levalbuterol
    Levalbuterol
    Levosalbutamol or levalbuterol , trade name Xopenex, is the R-enantiomer of the short-acting β2-adrenergic receptor agonist salbutamol. It is marketed by Cipla as Levolin, & by axa named Axazest.-Uses:...


Additional notes

  1. S

External links