Levalbuterol
Encyclopedia
Levosalbutamol or levalbuterol (USAN
), 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.
, it is used to treat asthma
and COPD
. In general, levosalbutamol has similar pharmacokinetic
and pharmacodynamic
properties to salbutamol
; however, its manufacturer, Sepracor
, has implied (although not directly claimed) that the presence of only the R-enantiomer produces fewer side effects.
and to an increase in the intracellular concentration of cyclic-3', 5' -adenosine monophosphate
(cyclic AMP). The increase in cyclic AMP is associated with the activation of protien kinase
A, which in turn, inhibits the phosphorylation
of myosin
and lowers intracellular ionic calcium concentrations, resulting in muscle relaxation.
Levosalbutamol relaxes the smooth muscles of all airways, from the trachea
to the terminal bronchioles. Increased cyclic AMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways. Levosalbutamol acts as a functional antagonist
that relaxes the airway irrespective of the spasmogen involved, thereby protecting against all bronchoconstrictor challanges. While it is recognized that beta2-adrenergic receptors are the predominant receptors on brochial smooth muscle, data indicate that there are beta-receptors in the human heart, 10-50% of which are beta2-adrenergic receptors. The precise function of these receptors has not been established. However, all beta-adrenergic agonist drugs can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic (ECG).
There are differing opinions on whether there is sufficient therapeutic benefit to using levalbuterol that outweighs the 5-10 times higher price tag. In general, it appears that if a clinician and patient feel that a low dose of racemic mixture is causing undesirable side effects, levalbuterol may be a viable alternative.
and eventually become available as a CFC
-free metered dose inhaler
under the trade name "Xopenex HFA (levalbuterol tartrate
) Inhalation Aerosol". The FDA
approval date was on March 11, 2005. (See Official FAQ)
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...
), trade name Xopenex, is the R-enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
of the 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:...
salbutamol
Salbutamol
Salbutamol or albuterol 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....
. It is marketed 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 Levolin, & by axa named Axazest.
Uses
As a bronchodilatorBronchodilator
A bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs. Bronchodilators may be endogenous , or they may be medications administered for the treatment of breathing difficulties...
, it is used to treat 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 COPD
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...
. In general, levosalbutamol has similar pharmacokinetic
Pharmacokinetics
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...
and pharmacodynamic
Pharmacodynamics
Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect...
properties to salbutamol
Salbutamol
Salbutamol or albuterol 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....
; however, its manufacturer, Sepracor
Sepracor
Sepracor, Inc. is a pharmaceutical company founded in 1984 by Tim Barberich. It was originally located in Princeton, New Jersey and then re-located to Marlborough, Massachusetts. On October 12, 2010, the company changed its name to Sunovion.-Company history:The company's initial focus was on the...
, has implied (although not directly claimed) that the presence of only the R-enantiomer produces fewer side effects.
Pharmacodynamics
Activation of beta2-adrenergic receptors on airway smooth muscle leads to the activation of adenylate cyclaseAdenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....
and to an increase in the intracellular concentration of cyclic-3', 5' -adenosine monophosphate
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...
(cyclic AMP). The increase in cyclic AMP is associated with the activation of protien kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
A, which in turn, inhibits the phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
of myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
and lowers intracellular ionic calcium concentrations, resulting in muscle relaxation.
Levosalbutamol relaxes the smooth muscles of all airways, from the trachea
Trachea
Trachea may refer to:* Vertebrate trachea, or windpipe, in terrestrial vertebrates, such as birds and mammals* Invertebrate trachea, in terrestrial invertebrates, such as insects and crustaceans* Vessel elements in plants...
to the terminal bronchioles. Increased cyclic AMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways. Levosalbutamol acts as a functional antagonist
Antagonist
An antagonist is a character, group of characters, or institution, that represents the opposition against which the protagonist must contend...
that relaxes the airway irrespective of the spasmogen involved, thereby protecting against all bronchoconstrictor challanges. While it is recognized that beta2-adrenergic receptors are the predominant receptors on brochial smooth muscle, data indicate that there are beta-receptors in the human heart, 10-50% of which are beta2-adrenergic receptors. The precise function of these receptors has not been established. However, all beta-adrenergic agonist drugs can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic (ECG).
Preference over salbutamol
The use of levosalbutamol over the more traditionally used racemic salbutamol is controversial among health care professionals. That using levosalbutamol instead of salbutamol produces less direct effect on β1-adrenergic receptors and/or fewer cardiac side effects has been suggested, but not consistently demonstrated by long term, well-designed clinical trials.There are differing opinions on whether there is sufficient therapeutic benefit to using levalbuterol that outweighs the 5-10 times higher price tag. In general, it appears that if a clinician and patient feel that a low dose of racemic mixture is causing undesirable side effects, levalbuterol may be a viable alternative.
Approval
Levalbuterol was originally available only as a solution for nebulizerNebulizer
In medicine, a nebulizer is a device used to administer medication in the form of a mist inhaled into the lungs....
and eventually become available as a CFC
Chlorofluorocarbon
A chlorofluorocarbon is an organic compound that contains carbon, chlorine, and fluorine, produced as a volatile derivative of methane and ethane. A common subclass are the hydrochlorofluorocarbons , which contain hydrogen, as well. They are also commonly known by the DuPont trade name Freon...
-free 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 ...
under the trade name "Xopenex HFA (levalbuterol tartrate
Tartrate
A tartrate is a salt or ester of the organic compound tartaric acid, a dicarboxylic acid. Its formula is O−OC-CH-CH-COO− or C4H4O62−.As food additives, tartrates are used as antioxidants, acidity regulators, and emulsifiers...
) Inhalation Aerosol". The FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
approval date was on March 11, 2005. (See Official FAQ)