This paper will focus on the difference between two bronchodilators, Albuterol versus levalbuterol in Asthma. This paper have discussed the various studies that have been carried out by different researcher in order to find the difference between the two bronchodilators. According to these studies, Levalbuterol seems to progress pulmonary task to a faintly better degree and last slightly longer than racemic Albuterol for the equal dose of R-Albuterol. The development in pulmonary role is related to 2.5 mg of racemic Albuterol and 0.625 mg of Levalbuterol with reduced toxicity with the second. Albuterol general toxicity follows the total amount of R-Albuterol there in a particular preparation. To add to this, there seems to be a better overall expenditure savings with Levalbuterol in comparison to racemic Albuterol. The expenditure savings appears to be connected to a decrease in duration of hospital stay and a decrease in the entire nebulization therapy when Levalbuterol is applied in relation to racemic Albuterol. The etiologic causes in these variations are vague, but might be linked to the S-Albuterol available in one preparation than in the other. According to studies, it is apparent that both albuterol and Levalbuterol are effective and safe, whilst employed in constant form in the treatment of asthma. Nevertheless, studies have revealed that albuterol might be superior compared to Levalbuterol.
For decades, inhaled β-agonists, including racemic Albuterol have been evidenced to be the basis of therapy of asthma exacerbation. Albuterol encompasses the same amount of contents of two enantiomers- (S)-Albuterol and (R)-Albuterol (Volcheck et al., 2005; Ralston et al., 2005). Some clinicians perceived that (R)-isomer was to blame for the bronchodilatory impacts of racemic Albuterol in addition to other side impacts including vomiting, tachycardia and tremor. The (S)-isomer was deemed of being biologically dormant. Studies carried out contemporarily revealed that in the racemic mixture, the S-enantiomer might amplify airway hyperresponsiveness and, activate eosinophils, impacts that might turn out being harmful to asthmatics (Volcheck et al., 2005). Presently, A B-agonist that comprise of levalbuterol is commercially available. In the past ten years, various studies have been conducted to compare the efficiency of various doses of racemic Albuterol with Levalbuterol the treatment of asthma exacerbations frequently with conflicting outcomes (Ralston et al., 2005). The efficacy and safety of Levalbuterol in the treatment of asthma has been established very well. It has been shown that it is frequently advantageous to make use of continuous or larger treatments which contains β-agonists for controlling considerable asthma exacerbations efficiently ad more quickly in emergency rooms (Carl et al., 2003). According to Carl et al (2003), studies have also been carried out to compare racemic Albuterol with chronic-dose nebulized Levalbuterol in the inpatient situation. This research paper will focus on Albuterol versus Levalbuterol in Asthma.
Description of Asthma
Asthma is the general chronic disease that affects the airways, which have the role of carrying air in and from the lungs (Mason et al., 2005). The disease is characterized by recurring and variable symptoms including coughing, wheezing, breath shortness and chest tightness. The disease is classified as non-atopic or atopic; or according to (FEV1). Asthma is believed to be caused by a mixture of environmental and generic factors (Mason et al., 2005). The symptoms can be avoided by preventing triggers and they can also be treated using various medications.
There are two medications that are used to treat asthma: long-term control applied to prevent supplementary exacerbation, and quick-relief that is applied to treat the symptoms of acute. The first line for treating the symptoms of asthma is the short acting beta2 –adrenoceptor agonists (SABA), likes albuterol and levalbuterol. In case of severe symptoms, which cannot be controlled by SABA, anticholinergic like ipratropium bromide can be applied in order to provide an extra value. For the long-term control, glucocortcoids treatments are the effective ones in asthma. Long acting beta-adrenoceptor agonists (LABA) can also be applied, as they can work for about 12 hours effectively. The LABA is only used together with a steroid as a result of overwhelmed jeopardy of the stern symptoms. There are other alternative to gasped glucocorticoids, which are not very much preferred, such as mast cell stabilizers (i.e cromolyn sodium) and leukotriene (i.e zafirlukast).
Albuterol is normally used by the inhaled path for exact upshot on bronchial downy muscle. This is attained through a neubulizer and metered dose inhaler among other delivery devise. Levalbuterol relaxes the fine muscles of the entire airways, starting from the trachea up to the terminal bronchioles. Levalbuterol works like a pratical antagonist, which causes a relaxation in the airway despite the involvement of the spasmogen, thus shielding the challenges of bronchoconstrictor. The side effect of Albuterol and Levalbuterol is that they can cause cardiovascular in some patients, as measured by blood pressure, pulse rate, symptoms and electrocardiographic. The physical structure and actual chemical is the only difference between the Albuterol from Levalbuterol (Gumbhir-Shah et al, 1998).
According to studies, Levalbuterol development is based on its advantages over the racemic Albuterol. They include; lesser episodes of the ephemeral tachycardia, a higher efficacy as well as a better tolerability (Hulisz, 2010). Schreck and Babin (2005) designate the patients who benefit most from the Levalbuterol treatment. In the pediatric and adult asthmatic patients, laboratory test have revealed that there is a lower average heart rate in the patients using Levalbuterol as compared to those using Albuterol. It is apparent that the degree of the difference is diffident (Ralston et al., 2005). Its use could be of paramount to patients having a history of structural heart disease, arrhythmias, or cardiac conditions such as the decompensated heart failure, which could get worse with a tachycardia episode (Hulisz, 2010).
According to some scholars, there is no notable difference in the average heart rate if both the Albuterol and Levalbuterol medication are compared head to head (Hulisz, 2010). Due to the fact that severe impacts of high heart rate are a common phenomenon to all the equimolar doses and beta agonists of the racemic Albuterol and Levalbuterol are projected to lead to the same extent of tachycardia (Schreck and Babin, 2005). According to Schreck and Babin (2005) whether levalbuterol is tolerated well than albuterol is somewhat controversial. It is evident that chronic dose of racemic Albuterol have a number of adverse effects which include tachyphylaxis, hypokalemia, and high mortality rate. The S- Albuterol does not have bronchodilator activity. Its metabolism process is 10 times slower as compared to that of Levalbuterol (Hulisz, 2010). Researchers have theorized those negative effects as proinflammatory effects and the worsening airway reactivity. It leads to preferential accumulation of the (S)-isomer over (R)-albuterol in the lung, potentially resulting in paradoxical bronchospasm (Hulisz, 2010).
A group of researchers (Carl et al., 2003) performed a comparison of the impacts of nebulized Levalbuterol with those of racemic Albuterol in 627 adults who were suffering from chronic asthma. Randomly, the patients were assigned to receive Albuterol and Levalbuterol 2.5mg and 1.25mg respectively every 20 min upon emergency admission, and then, 40 min for at least 3 additional doses, and then, as frequently as clinically required for twenty-four hours. All patients were also given prednisone 40mg (Carl et al., 2003). Levalbuterol heightened forced expiratory volume by about 40 percent as compared the racemic Albuterol. This resulted to a 40% reduction necessary hospitalization as compared to the Albuterol. The benefits of the Levalbuterol were apparent particularly to the patients with chronic asthma and had high levels of S- Albuterol that is higher than 1095mg/ml (Carl et al., 2003). As revealed by studies, increased circulating levels of the S- Albuterol are perceived to be a consequence of an overdose of racemic Albuterol. The number of asthma relapses that occurred 30 days after acute exacerbation did not differ between the 2 groups (Hulisz, 2010). Apparently, the numbers of nebulizations required with Levalbuterol were lesser (Hulisz, 2010). There was no need to increase the for rescue aerosols during the 14 days of hospitalization.
Another study carried out by Ralston et al (2005 on the hospitalized asthmatic patients, similar conclusions were reached. It is quite evident that the Levalbuterol benefits over Albuterol benefits were more on the moderate to severe asthmatic patients and in particular, those who had taken Albuterol in excess (Volcheck et al., 2005). Comparing Albuterol and Levalbuterol, it is vital to consider their costs. Before the year 2009, generic formulations of Albuterol metered-dose inhaler (MDI) was extensively available and in fact was much cheaper compared to branded Albuterol such as Ventolin®, Proventi®, and Levalbuterol (Hulisz, 2010). Most metered-dose inhaler formulations consisted of chlorofluorocarbons and in addition, they are not currently available for commercial use as the Food and Drug Administration prohibited them as a result of environmental reasons. Generic Albuterol MDI is not presently available in the market. On the other hand, Levalbuterol nebulization is significantly more expensive compared to Albuterol nebulization (Volcheck et al., 2005; Schreck and Babin, 2005).
As a result of the study limitations and the increased costs of Levalbuterol, for instance, inadequate power and small sample size, some individuals have wind up that the employment of Levalbuterol instead of Albuterol is not greatly backed by the literature(Volcheck et al., 2005). Some people argue that Levalbuterol may be used in place of racemic Albuterol in various circumstances including the following:
- Patients who habitually experience troublesome tachycardia with Albuterol and do not like making use of it.
- Patients suffering from COPD or asthma among other simultaneous cardiac disease, and in particular if such conditions could possibly become worse with tachycardia, for instance, decompensated heart failure, inadequately controlled cardiac arrhythmias, and valvular heart disease.
- Patients who have asthma that is more critical and who require recurrent doses of a beta-2 agonist in spite of suitable employment of controller therapies (Hulisz, 2010).
In comparing the two kinds of asthma treatments, which include the Albuterol and the Levalbuterol, a study was performed on 362 asthmatics of 12 years and above. At random, the subjects received the nebulized treatment at least three times per day. The dosage was as follows; Levalbuterol 0.625 mg, Levalbuterol 1.25 mg, 1.25 mg of racemic Albuterol, 2.5 mg of racemic Albuterol, or placebo(Gumbhir-Shah et al,1998). Serial pulmonary function testing with spirometry was performed after two and four weeks respectively (Gumbhir-Shah et al, 1998).
The main change in the FEV1 was remarkably higher than that of placebo for the initial dose given to all the treated groups. The average peak change in FEV1 at baseline was as follows 0.92 and 0.82L, respectively; p=0.03 (Van Essen-Zandvliet and Hughes, 1992). This was a change noticed not after the four weeks and it was evidently found to be higher in the combined group of Levalbuterol as compared to the combined group of racemic Albuterol. In order to establish the result of chronic dosing on the functioning of the lungs, the average prior dose FEV1 at the fourth week in a comparison made at the baseline for all patients and for the subset of patients who did not receive inhaled corticosteroids was examined (Van Essen-Zandvliet and Hughes, 1992). There was a 0.1-liter improvement (about 6%) in predose FEV1 in the subjects receiving Levalbuterol and those on placebo and none in subjects on racemic Albuterol (Van Essen-Zandvliet and Hughes, 1992). In the case of patients who are not on inhaled corticosteroids, there was a difference of a 0.13 and 0.31 which is equivalent to 7 and 15% respectively dissimilarity between pre-dose FEV1 in subjects getting 0.625 mg and 1.25 mg of Levalbuterol when related with the ones getting 1.25 and 2.5 mg of racemic Albuterol, correspondingly. As noted the best development was in the 1.25 mg Levalbuterol section of the study. The later findings suggest in exact that constant dosing with racemic Albuterol may in real sense slow down functions of the lung as the 4-week pulmonary function values were a bit lower than bottom line in the racemic Albuterol group
Side effects comprised of a raise in heart rate following dosing which was considerably more for racemic Albuterol 2.5 mg in comparison to Levalbuterol 0.625 mg at 4 weeks regardless of related improvements in the functions of the pulmonary (Gumbhir-Shah et al, 1998). The rescue Albuterol cure cutback was also relatively lower simply in the Levalbuterol 1.25 mg faction (Van Essen-Zandvliet and Hughes, 1992). There is a development in the function of the lung following dosing with Levalbuterol 1.25 mg> Levalbuterol 0.625 mg = racemic Albuterol 2.5 mg>racemic Albuterol 1.25 mg. Additionally, rescue Albuterol prescription application was slighter with the Levalbuterol 1.25 mg organization and there is a proposal of a decrease in the function of the lung with constant dosing occurring with racemic Albuterol (in relation to placebo).
A less double blind single dose, dose- range research studied asthmatics in 20 cases in a five-way intersect studying at effectiveness of three doses of Levalbuterol(0.31, 0.63 and 1.25mg), placebo and racemic Albuterol at 2.5 mg nebulization (Keir et al, 2002). The major result variables were: 1) the general adjustment in FEV1 from pre-dose to 6 hours post-dose, 2) the point to commencement of bronchodilation distinct as point from dosing waiting at least a 15% progress in FEV1 was noted, 3) the period of outcome, or the period the FEV1 was maintained over bottom line(Gumbhir-Shah et al, 1998).
All the dynamic cure groups registered an improvement in FEV1 of 28-32% (more than 15%) in 15 minutes of treatment in comparison with placebo. The development in FEV1 over 15% was maintained for like 4 hours in the Levalbuterol 0.63 and 1.25 mg groups and in the racemic Albuterol group. The highest period of outcome for upholding an FEV1 over 15% of predose was with Levalbuterol 1.25 mg (mean time of 275 minutes), then Levalbuterol 0.63 mg (mean time 237 minutes) and racemic Albuterol 2.5 mg(mean time 221 minutes).
Another dose ranging research involving 20 cases of asthma in a random, double-blind, 4-way intersect research made of 4 learning days each one divided by at lest 3 day failure period was carried out and Glaxo, a maker of racemic Albuterol, supported it (Keir et al, 2002). On a particular day these doses were given in an increasing manner at 25 minute intervals: 6.25, 12.5, 25, 50, 100, 200, 400, 800, and 1,600ug for R-or S-Albuterol and 12.5, 25, 50, 100, 200, 400, 800, 1,600, and 3,200ug for (R, S)-Albuterol together with placebo doses single day in the 4 days. The findings of the research evidently demonstrate a dose-related progress in FEV1 and consequences reliant on the quantity of (R)-Albuterol substance only, if or not (R)-Albuterol or (R, S)-Albuterol was utilized. None of the results were noted with (S)-Albuterol or placebo.
A study based on pediatric researched on racemic Albuterol and Levalbuterol in 28 cases of children with asthma aged between 6 to 11 (Keir et al, 2002). The research was a random double blind intersect study looking at single doses in groups of seven: 0.16, 0.31, 0.63, and 1.25 mg of Levalbuterol, placebo, and 1.25 and 2.5 mg of racemic Albuterol. Visits were programmed from 2 to 8 days spaced out with sequential dimensions of spirometry at bottom line to 6 hours post inhaling dose. Racemic Albuterol was withdrawn for not less than 8 hours to the research.
Clear results in the research were bigger progress in the function of the lung with 1.25 mg of Levalbuterol in comparison to 2.5 mg of racemic, Albuterol and what seemed to be a simple dose reaction connection between serum treatment levels of Levalbuterol and function of the lung, a thing that has not been there previously when using Albuterol. Effects of the heart rate depended on the dose of Levalbuterol administered (Gumbhir-Shah et al, 1998).
A great study based on pediatrics assessed constant dosing with Levalbuterol and racemic Albuterol in asthmatics cases of 338 pediatrics, aged between 4 and 11 years (Keir et al, 2002). Qualified cases were administered nebulization for three times a day treatment for twenty-one days for one of the 5 treatments: Levalbuterol 0.31 or 0.63 mg, placebo, or racemic Albuterol at 1.25 or 2.5 mg. The trial was a random, double blind. The major endpoint was FEV1 climax percent modification on the 21st day past treatment in comparison to bottom line prior to cure on the zero day.
All the dynamic treatments became better considerably in comparison to placebo on the 21st day similar to the major endpoint. Levalbuterol at doses of 0.31 and 0.63 mg seemed to be alike in result to racemic Albuterol at 1.25 and 2.5 mg with related or fewer consequences. It was suggested that asthmatic children aged 4 to 11 were supposed to start with a dose of Levalbuterol of 0.31 mg once administered for soft to temperate constant asthma (Gumbhir-Shah et al, 1998).
An extremely fascinating demonstration chart evaluation research undertaken, made use of a hospital’s changeover strategy in the application of Albuterol (Gumbhir-Shah et al, 1998)). The research looked at Albuterol application in the two 6-month periods July 1 to December 31, 1998 and July 1 to December 31, 1999. The principal proven endpoint of the research was the entire amount of nebulizer treatments essential of patients admitted in hospitals with COPD or asthma in those two point periods. In the primary time stage, only racemic Albuterol was applied for nebulization at 2.5 mg every 4 hours as required medically. In the other time stage, the hospital switched over to Levalbuterol nebulization of 1.25 mg every 8 hours as required medically.
Patients treated using Levalbuterol needed considerably less β2-agonist and ipratropium bromide treatments in hospitalized sick ones in relation to racemic Albuterol (Gumbhir-Shah et al, 1998)). It translated to an average entire price of nebulizer therapy that was considerably bigger in patients hospitalized with COPD and asthma in racemic Albuterol patients treated in comparison to Levalbuterol administered patients. After calculating for analysis, bottom-line FEV1, and ipratropium application, Levalbuterol was related with a lessened span of stay in the hospital, overall cost reserves and a reduction in the possibility of readmission in hospitals.
In general, Levalbuterol seems to progress pulmonary task to a faintly better degree and last slightly longer than racemic Albuterol for the equal dose of R-Albuterol. The development in pulmonary role is related to 2.5 mg of racemic Albuterol and 0.625 mg of Levalbuterol with reduced toxicity with the second. Albuterol general toxicity follows the total amount of R-Albuterol there in a particular preparation. To add to this, there seems to be a better overall expenditure savings with Levalbuterol in comparison to racemic Albuterol. The expenditure savings appears to be connected to a decrease in duration of hospital stay and a decrease in the entire nebulization therapy when Levalbuterol is applied in relation to racemic Albuterol. The etiologic causes in these variations are vague but might be linked to the S-Albuterol available in one preparation than in the other. According to studies, it is apparent that both albuterol and Levalbuterol are effective and safe whilst employed in constant form in the treatment of asthma (Schreck and Babin, 2005). Nevertheless, studies have revealed that albuterol might be superior compared to Levalbuterol.