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Pharmacology: Uses of Albuterol and β2-Adrenergic Agonist

Introduction

Albuterol is generally used for treating reactive airway deceases. This remedy is also known as salbutamol, and its main predestination is the relief of bronchospasm in the case of such diseases like asthma or chronic obstructive pulmonary disease. The optimal frequency of albuterol usage is generally subjected to numerous researches, and it should be stated that studies, associated with the optimal frequency of administration, are generally based on the personal requirements of each patient, and the possible side effects of overdosing.

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This paper is aimed at reviewing research articles aimed at studying the use of albuterol and β2 adrenergic receptor agonist and defining the optimal frequency of its usage. These researches are focused on asthma treatment, the possible side effects of using β2 agonists, as well as the possible effects of combining β2 components with steroids. Another aspect of the researches is the frequency of administering albuterol: regular vs. as needed.

What is the optimal frequency for albuterol administration in the treatment of reactive airway disease: routine treatment or as-needed use?

Background

Previously to analyzing the possible variants of albuterol administration, the possible side effects should be reviewed. Therefore, as is stated by Cook, Guyatt et.al (2001, 87) the possible symptoms of overdosing and acute poisoning of albuterol are stenocardia, tachycardia (with the possible pulse of up to 200 strikes per minute), arrhythmia, vertigo, dry mouth, fatigue, headache, hyperglycemia (after hypoglycemia), increase or decrease of blood pressure, hypokalemia, insomnia, nausea, spasms, tremor. Considering the nature of albuterol, it should be stated that this is a short-acting selective agonist of β2 adrenergic receptors. As it is stated by Cook and Guyatt (2001, p, 87):

Salbutamol sulfate is usually given by the inhaled route for a direct effect on bronchial smooth muscle. This is usually achieved through a metered-dose inhaler, nebulizer, or other proprietary delivery devices. 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 or intravenously.

Therefore, the usual dose prescribed for bronchospasm prevention is 1-2 inhalations every 4-5 hours, if the drug is taken in aerosol form. The dose for nebulizer is 0.63 mg, 1.25 mg, or 2.5 mg 3-4 times a day. As for tablets or syrups, it is recommended that dosing did not overwhelm 2-4 mg 3-4 times daily. Therefore, if the instance of asthma or chronic bronchial obstructive attacks is more frequent, the obvious result of albuterol administering is clear. However, the question of optimal frequency stays open.

It should be stated that the question of frequency has been already arising. Therefore, in some researches before 1990 most scientists recommended regular usage of beta-agonists, however, this was acceptable for mild asthma treatment only. However, Sears’ (1993) research (in Drazen, Israel, 1996)reported that regular usage of β-agonists was featured with the decreased control level, and it may even increase the morbidity level

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Literature Review

Barnes (1995) emphasizes that most patients with asthma are treated with beta-2 agonists in junction with steroids, while this helps to control asthma better. The research is focused on studying the effect of fixed combinations, while the frequency of albuterol administration was regarded as the secondary aspect of the research. In order not to consider severe cases of asthma, and exclude the possible overuse of beta-2 agonists because of frequent asthma attacks, mild to moderate asthma cases were regarded for this research.

The key statement on the matters of regularity is based on the fact that this depends on the dose of beta-2 components, as well as using of additional bronchodilators. While few patients require these additions, there is no need to follow precise regularity. However, if the doses are too high, the risk of overdosing may be rather high, consequently, β2 adrenergic receptors should be taken periodically. As it is stated by Barnes (1995, p. 1053):

Inhaled steroids provide no immediate improvement in asthma symptoms, so patients may perceive this treatment to be relatively ineffective as an anti-asthma medication. In contrast, inhaled β2 agonists give rapid relief of asthma symptoms; therefore, this treatment is preferred.

In light of this fact, it should be stated that such an approach may cause the overuse of β2 agonists.

Considering the results of the study, it should be emphasized that each patient was offered an individual combination of beta 2 agonist and steroidal drug, however, mild asthma patients required low-dose short-acting β2, while the frequency of taking these doses was different. It was stated that there is no need for patients with mild asthma to take drugs periodically, while as-needed consumption was the optimal variant that helps to cope with the attack and avoid overdosing. Additionally, it was stated that regular use of fenoterol is featured with poorer control of asthma in comparison with on-demand use.

Long-acting inhaled beta-2 agonists do not have an anti-inflammatory effect, in comparison with inhaled steroids, therefore, their use is often combined, however, they are rarely used for treating asthma, and they often require regular usage (Drazen, Israel, et.al., 1996).

Heino emphasizes that if asthma is moderate to severe, regular use of beta-agonists may be regarded as normal. The research was based on studying morning and evening peak expiratory flows that had been recorded daily for one week. β2 agonists and steroids had been used regularly during this week and used as needed for the next two weeks. As Heino states (1994, p. 80):

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The mean evening PEF values were significantly higher (difference = 9.55 L/min: p = 0.017: 95% confidence interval, 1.80 to 17.30 L/min, and the mean morning PEF values were nearly significantly higher (difference = 6.49 L/min; p = 0.088, 95% CI, – 0.99 to 14.00 L/min) during regular β2 agonist use.

Hence, it may be stated that regular use of short-acting beta 2 agonists is often regarded as a small benefit for patients. Chronic Obstructive Pulmonary Decease may be complicated with the regular usage of these agonists. Considering the results of the study, it should be emphasized that the actual importance of regular usage of beta 2 agonists is associated with the fact that long-acting agonists are intended for offering better control over asthma attacks, while COPD instances can not be subjected to better control. COPD requires the regular taking of beta 2 agonists, though, this therapy is often enforced with taking steroids. As for asthma, the given doses appeared to be more effective while taking them on an as-needed basis. However, the results may be distorted because some patients did not record all the symptoms, and failed to register all the necessary data for the research.

Therefore, by the research by Heino (1994), the results of randomized research with placebo-controlled crossover, involved regular albuterol therapy (2 puffs four times daily, with the 100 µg per puff dosage), revealed that patients who used regular short-acting beta-agonists inhaling revealed worse results in comparison with those who inhaled on an as-needed basis.

By Charpman, Kesten, and Szalai (1994), it should be stated that the actual importance of regular usage of albuterol (inhaled beta 2 agonists) is explained by the fact that mild severe instances of asthma can not be treated by as-needed taking. Therefore, regular inhaling of long-acting agonists will be more helpful, as this approach helps control the worseni9ng peak-flow rates, increased asthma symptoms, as well as the necessity of taking supplementary bronchodilators. The dosage, which was stated for this research is 200 µg per 2 puffs, four times daily. Patients were required to take salbutamol for two weeks on an as-needed basis, and two weeks on regular basis. Hence, Charpman, Kesten and Szalai (1994, p. 1379):

There were no significant differences in morning and evening peak-flow rates between treatments, but asthma symptoms and supplementary bronchodilator use were less frequent when salbutamol was given regularly. Asthma episodes occurred 1 39 (1 52) times per day during regular treatment and 2 44 (1 75) times per day during as-needed treatment. In 70 asthmatics there was no difference in symptom control between periods but in the remainder, control was achieved more often by regular than by as-needed salbutamol.

Additionally, it was stated that in the case of moderate asthma instance, regularly administered salbutamol is not featured with lower peak flow rates. Therefore, regular taking of salbutamol is suitable for less frequent asthma attacks. As it is seen, the study involves pure salbutamol taking, without enforcing the treatment with steroids, however, those patients that require steroids reveal different results in the peak flow rates. Therefore, the dosage of beta 2 agonists, jointly with steroids will be different, depending on the severity of asthma instance, as well as the individual requirements of a patient. The list of commonly accepted inhaled steroids is as follows:

  • Advair
  • Aerobid
  • Azmacort
  • Dulera
  • Flovent
  • Symbicort
  • Qvar

It is not recommended to use these steroids regularly to avoid overdosing. That is why, if therapy presupposes taking beta 2 agonists jointly with steroids, these are taken on an as-needed basis if the asthma severity is mild to moderate, and regularly (with clearly prescribed periods), if the case is severe enough. Because the doses prescribed are the lowest, the possible side effects will be minimal or avoided at all. However, the research by Charpman, Kesten, and Szalai (1994) does not involve the possibility of steroids taking, while the actual regularity studied is 2 inhales 4 times a day.

The research by Ernst, Hhabbick, Suissa et.al. (1993), is focused on studying taking the inhalers in the case of risk of asthma death and near-death instances. This research was not focused on the regularity of the taking remedies, as the key objective of the research is to study which beta-agonists were used for preventing the studied severe asthma attacks. The two variants that were subjected to research are fenoterol and albuterol.

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Therefore, it is stated that most patients who suffered severe asthma were prescribed to take them regularly. The risk of fatal asthma attacks was associated with the physical parameters of each patient, his/her smoking, eating, behavioral habits, as well as the history of asthma treatment with the medicals prescribed. It is stated that most patients who had an instance (or several instances) of risk of death because of asthma attacks were prescribed to take beta 2 agonists regularly. However, some non-smokers with such instances took albuterol on an as-needed basis. The case does not involve the joint taking of beta 2 agonists with inhaled steroids.

Sears, Taylor, Print, et.al. (1990) are focused on studying patients with bronchial asthma by prescribing inhaled beta-agonists. Therefore, as it is emphasized in the results (1990, p.1391):

Of 64 patients who completed the study, 57 showed a clear difference in the degree of control of asthma between the fenoterol and placebo periods: in 17 asthma was better controlled during regular inhaled bronchodilator treatment, whereas in 40 control was better during placebo treatment with bronchodilator for symptom relief only. The adverse effect of regular bronchodilator inhalation occurred not only among subjects who used a bronchodilator as the sole treatment but also among those who took inhaled corticosteroids, while 14 patients revealed better results and 29 worse.

Some of the patients had to withdraw from the study, as they had to start taking oral steroids. By the given results, most of those who had to withdraw were taking a placebo, and the others were assigned with fenoterol. The requirements of the study did not involve the opportunity of as-needed taking of the remedies, therefore, all the results are given for regular use of the beta 2 agonists, as well as placebo taking. Nevertheless, it should be stated that regular inhalation of the prescribed drugs was featured with poorer overall control in the cases of chronic asthma. Even though PERF improved during regular treatment, all other parameters showed better results if the treatment was performed on an as-needed basis.

Conclusion

The matter of regularity in taking beta 2 agonists while treating asthma or bronchospasms which is a symptom of a chronic obstructive pulmonary disease depends on the dosage, enforcing the treatment with taking inhaled or oral steroids, as well as the severity of the asthma case. As a rule, most researches that are focused on studying the regularity of taking remedies involve setting a restricted dose of the remedy, while those researchers that include the possibility of taking steroids with the main remedy, or placebo instead of beta 2 agonists are mainly focused on the effectiveness of these prescriptions depending on the severity of the case.

Therefore, the main results of the literature review may be based on the fact, that most researchers have come to the result that regular taking of albuterol in the case of mild to moderate asthma is featured with the decreased asthma control, while severe and very severe cases require the regular taking of beta-2 agonists, jointly with steroids. This is explained by the fact that regular taking of maximal allowed doses helps to avoid overdosing. The maximal dose accepted for the studies is two puffs four times a day (200 µg per 2 puffs)

Reference List

Cook, Deborah; Guyatt, Gordon. Regular Versus As-Needed Short-Acting Inhaled beta -Agonist Therapy for Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2001 Volume 163, 85-90.

Drazen, Jeffry; Israel Elliot. Comparison of Regularly Scheduled with As-Needed Use of Albuterol in Mild Asthma. N Engl J Med 1996. VOl. 335 pp.841-847.

Barnes, Peter; O’Connor, Brian. Use of a fixed combination Beta 2-agonist and Steroid Dry Powder Inhaler in Asthma. Am J. Respir Care Med. 1995 Vol. 151 pp.1053-1057.

Heino, Matti. Regularly inhaled Beta-agonists with steroids are not harmful in stable asthma. Journal of Allergy Clinical Immunology. 1994 Vol. 93 pp.80-85.

Chapman, Kenneth; Kesten Steven; Szalai John. Regular vs as-needed inhaled salbutamol in asthma control. The Lancet Journal. 1994. 343. pp. 1379-82.

Ernst, Pierre; Habbick, Brian; Suissa, Samy. Et.al. Is the Association Between Inhaled Beta-Agonist Use and Life-Threatening Asthma Because of Confounding by Severity. American Review of Respiratory Disease. 1993 vol. 148. pp. 75-95.

Sears, R. Malcolm; Taylor, Robin; Print, Cristin. Regular inhaled beta-agonists treatment in bronchial asthma. The Lancet Journal 1990. 336: 1391-96.

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