Levosalbutamol, also known as levalbuterol, is a short-acting β₂ adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Evidence is inconclusive regarding the efficacy of levosalbutamol versus

salbutamol Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing rel ...

or salbutamol-levosalbutamol combinations, however levosalbutamol is believed to have a better safety profile due to its more selective binding to β₂ receptors (primarily in the lungs) versus β₁ (primarily in heart muscle). The drug is the (''R'')-(−)-

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

of its

prototype drug In pharmacology and pharmaceutics, a prototype drug is an individual drug that represents a drug class – group of medications having similar chemical structures, mechanism of action and mode of action. Prototypes are the most important, and typica ...

. It is available in some countries in generic formulations from pharmaceutical companies including Cipla, Teva, and Dey, among others.

Medical use

Levosalbutamol's bronchodilator properties give it indications in treatment of COPD ( chronic obstructive pulmonary disease, also known as chronic obstructive lung disease) and asthma. Like other bronchodilators, it acts by relaxing smooth muscle in the bronchial tubes, and thus shortening or reversing an acute "attack" of shortness of breath or difficulty breathing. Unlike some slower-acting bronchodilators, it is not indicated as a preventative of chronic bronchial constriction.

Comparison to salbutamol

A 2013

systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...

of the drug's use as a treatment for acute asthma found that it "was not superior to albuterol regarding efficacy and safety in subjects with acute asthma." The review concluded: "We suggest that levalbuterol should not be used over albuterol for acute asthma." Levalbuterol is notably more costly.

Adverse effects

Generally, levosalbutamol is well tolerated. Common mild side-effects include an elevated heart rate, muscle cramps, and gastric upset (including heartburn and diarrhea). Symptoms of overdose in particular include: collapse into a seizure; chest pain (possible precursor of a heart attack); fast, pounding heartbeat, which may cause raised blood pressure (

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

); irregular heartbeat ( cardiac arrhythmia), which may cause paradoxical lowered blood pressure ( hypotension); nervousness and

tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...

; headache; dizziness and nausea/vomiting; weakness or exhaustion ( medical fatigue); dry mouth; and insomnia. Rarer side effects may indicate a dangerous allergic reaction. These include: paradoxical bronchospasm (shortness of breath and difficulty breathing); skin itching, rash, or hives ( urticaria); swelling ( angioedema) of any part of the face or throat (which can lead to voice hoarseness), or swelling of the extremities.

Pharmacology

Mechanism of action

Activation of β₂ adrenergic receptors on airway smooth muscle leads to the activation of adenylate cyclase and to an increase in the intracellular concentration of 3',5'-cyclic adenosine monophosphate (cyclic AMP). The increase in cyclic AMP is associated with the activation of protein

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

A, which in turn, inhibits the

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

myosin Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility. The first 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

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

that relaxes the airway irrespective of the spasmogen involved, thereby protecting against all bronchoconstrictor challenges. While it is recognized that β₂ adrenergic receptors are the predominant receptors on bronchial smooth muscle, data indicate that there are beta receptors in the human heart, 10–50% of which are β₂ adrenergic receptors. The precise function of these receptors has not been established. However, all β adrenergic agonist drugs can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, and restlessness symptoms, and/or electrocardiographic (ECG).

Approval and names

Levosalbutamol is the INN while levalbuterol is the USAN. Levalbuterol was approved in the United States as a solution to be used with a nebulizer device in March 1999 For updates and past labels, se
FDA index page for NDA 020837
and in March 2015 became available in a formulation with a metered-dose inhaler under the trade name Xopenex HFA (levalbuterol tartrate inhalation aerosol). For updates and past labels, se
FDA index page for NDA 021730

References

External links

* {{Portal bar , Medicine Beta2-adrenergic agonists Chemical substances for emergency medicine Enantiopure drugs Phenylethanolamines Phenols