Albuterol: An Adrenergic Agent for Use in the Treatment of Asthma Pharmacology, Pharmacokinetics and Clinical Use

Abstract

Albuterol is a long-acting beta 2-adrenergic receptor-selective drug that relaxes airway smooth muscle. It is currently available in the United States in oral and metered-dose inhaler forms. Nebulizer solutions and parenteral preparations are likely to be marketed here in the future. The chemical modifications that make albuterol beta 2-selective also promote oral bioavailability and increased duration of action by decreasing sensitivity to degradative enzymes. Albuterol can also produce undesirable dose-related effects: metabolic effects including decreased levels of plasma potassium, phosphate, calcium and magnesium; increased levels of plasma glucose, insulin, renin, lactate and ketones; peripheral vasodilation and perhaps some direct cardiac stimulation resulting in decreased systemic and pulmonary vascular resistance, increased pulse pressure and tachycardia; and skeletal muscle tremor. These side effects are most common with parenteral administration and much less prominent with aerosol administration, which yields lower systemic concentrations. Limited pharmacokinetic data suggest a long distribution phase, a terminal half-life of 3-8 hours, and 10-20% oral bioavailability. Aerosolization of albuterol or a similar agent with a compressed-air nebulizer appears to be best first-line management of the patient with acute dyspneic asthma, but appropriate preparations for this kind of therapy are currently missing from the United States market. Intravenous albuterol has also been employed in acutely dyspneic patients, but produces more side effects than carefully administered intravenous theophylline, is impaired by lack of sufficient pharmacokinetic information to guide dosing, and is of uncertain efficacy in the asthmatic with respiratory failure. However, it appears to lack the potentially life-threatening side effects that can result when theophylline is used carelessly . In the ambulatory patient, aerosolized albuterol (or a similar agent) administered by metered-dose inhaler is an excellent agent for treatment as needed and/or for prevention of acute bronchospasm triggered by exercise or other predictable cause. Advantages include a high degree of efficacy, rapid onset and long duration of effect, and minimal side effects. Regularly scheduled administration of albuterol by metered-dose inhaler is a widely used and effective maintenance medication for patients requiring long-term prophylactic therapy. However comparisons of the ability of this regimen and the other common maintenance regimens (cromolyn and theophylline) to control chronic symptoms of asthma are needed.

Plasma concentrations and effects of salbutamol administered orally to patients with cystic fibrosis.

“…The major route of elimination of orally administered salbutamol is conjugation with sulphate in the intestinal wall and liver [22,[28][29]. Previous studies have reported that sulphation of exogenous substrates and of endogenous macromolecules is increased in CF [13,30].…”

“…Eleven CF patients (aged [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] years; five females) and a control group of 10 healthy subjects (aged …”

Inhaled Insulin Using the AERx Insulin Diabetes Management System in Healthy and Asthmatic Subjects

“…Very real differences in serum insulin levels between the two groups could mask possible differences in insulin absorption if no C-peptide adjustment was conducted. It has been reported in the literature that inhaled ␤ 2 -agonists can increase insulin levels in asthmatic subjects (27)(28)(29), and thus the observed elevation of C-peptide level may be a direct result of chronic use of asthma medications. It is important to note that inhaled insulin did not exacerbate the baseline airway hyperreactivity state of asthmatic subjects in this study.…”

Long-Term Effects of Antepartum Bed Rest on Offspring

“…These drugs are believed to affect the immune system. Their effect is achieved by stimulation of adenyl cyclase which catalyzes conversion of ATP to cAMP [29]. An increase in cAMP results in relaxation of smooth muscle.…”