Beta-3 Agonists

The beta-1 receptor is located primarily on the myocardium, and stimulation of the receptor results in in- 

Dobutamine (Dobutrex). Dobutamine is used for short-term management of cardiac decompensation that sometimes occurs during exacerbations of heart disease or following cardiac surgery.28 This drug is often administered via intravenous pump infusion to allow relatively stable plasma levels. 

Because of their cardiostimulatory effects, beta-1-selective drugs may induce side effects such as chest pain and cardiac arrhythmias in some patients. Shortness of breath and difficulty in breathing (i.e., feelings of chest constriction) have also been reported. 

Ritodrine (Yutopar ]. The primary clinical application of this drug is to inhibit premature labor.22 Ritodrine activates uterine beta-2 receptors, which mediate relaxation of uterine muscle. This drug is usually administered initially via intravenous pump infusion, and maintenance therapy is accomplished through oral administration. There is little evidence, however, that ritodrine and other beta-selective ago- 

Exercise should only be considered when the subject knows that he or she will not be given a pop quiz in the near future. 

Studies have shown that Clenbuterol reduces fat, which would help rid lipid tissue of THC metabolities. Clenbuterol also increases metabolism. No studies have directly shown that Clenbuterol will help pass a drug test. However, provided that it reduces fat, 1 would assume that the fat breakdown would result in less fat soluble substances in the system. Caution Clenbuteral is labeled as a performance enhancer, and it s on the banned list for athlete testing. If are being tested as an athlete, avoid Clenbuterol  

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J. P. Hanrahan and co-workers, Beta-Agonists and Their Effects on Animal Growth and Carcass Quality, Elsevier Apphed Science, London, 1987, pp. 106-118. 

Attempts to diminish the overall metabolism of trichloroethylene might be useful (e.g., hypothermia, mixed-function oxidase inhibitors, competitive inhibitors of trichloroethylene metabolism [i.e., P-450 substrates]), if instituted soon enough after trichloroethylene exposure. Catecholamines (especially beta agonists) act in concert with trichloroethylene, increasing the risk of cardiac arrhythmias. Hence, catecholamines should be administered to patients only in the lowest efficacious doses and for certain limited presentations of trichloroethylene poisoning. Ethanol should also be avoided because concurrent exposure to trichloroethylene and ethanol can cause vasodilation and malaise and may potentiate central nervous system depression at high dosage levels of either compound. 

Worldwide Atosiban versus Beta-agonists Study Group. (2001) Brit. J. Obstet. Gynaec. 108, 133-142. 

Taylor DR, Drazen JM, Herbison GP, Yandava CN, Hancox RJ, Town GI. Asthma exacerbations during long term beta agonist use influence of beta[2] adrenoceptor polymorphism. Thorax 2000 55[9] 762 767. 

Caution Increasing use of beta-agonist or use >2 times a week for symptom control (not prevention of EIB) indicates inadequate control and the need to step up treatment. 

Relative extraction efficiencies of polar polymeric neutral, cation, and anion exchange sorbents (HLB, MCX, and MAX) for 11 beta antagonists and 6 beta agonists in human whole blood were probed.109 Initial characterization of MCX and MAX for acidic and basic load conditions, respectively, showed that both the agonists and antagonists were well retained on MCX, while they were recovered from MAX in the wash with either methanol or 2% ammonia in methanol (see Table 1.6). Blood samples were treated with ethanol containing 10% zinc sulfate to precipitate proteins and the supernatants loaded in 2% aqueous ammonium hydroxide onto the sorbents. After a 30% methanol and 2% aqueous ammonia wash, the analytes were eluted with methanol (HLB), 2% ammonia in methanol (MCX), or 2% formic acid in methanol (MAX). The best recoveries were observed with MCX under aqueous conditions or blood supernatant (after protein precipitation) spiked sample load conditions (see Table 1.7). Ion suppression studies by post-column infusion showed no suppression for propranolol and terbutaline with MCX, while HLB and MAX exhibited suppression (see Figure 1.6). 

Luo W, Grupp IL, Harrer J et al 1994 Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation. Cite Res 75 401 —409... 

Aerosolised medicines have been used for centuries to treat respiratory diseases, with inhalation therapy for the airways focused primarily on the treatment of asthma and chronic obstructive pulmonary disease (COPD). The development of new products for delivery to the lungs for these respiratory diseases includes new steroids and beta agonists plus combination products featuring both agents. New classes of anti-asthma medication are also being developed for inhalation with the aim of delivering them directly to the inflamed airways. 

Taylor DR, Sears MR, Herbison GP, et al. (1993) Regular inhaled beta agonist in asthma effects on exacerbations and lung function. Thorax. 48,134—138. 

Garrett JE, Lanes SF, Kolbe J, Rea HH. (1996) Risk of severe life threatening asthma and beta agonist type an example of confounding by severity. Thorax. 51, 1093-1099. 

Cho SH, Oh SY, Bahn JW, et al. (2005) Association between bronchodUating response to short-acting beta-agonist and non-synonymous single-nucleotide polymorphisms of beta-adrenoceptor gene. Clin Exp Allergy. 35, 1162-1167. 

McGraw DW, Almoosa KF, Paul RJ, Kobilka BK, Liggett SB. (2003) Antithetic regulation by beta-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway beta-agonist paradox. J Clin Invest. 112, 619-626. 

LTB4 is a potent bronchoconstrictor, as are several other leukotrienes. A 5-lip-oxygenase inhibitor, Zileuton, is approved for therapy of asthma (though it is not much used for this purpose) as is a leukotriene blocker, montelukast, marketed as Singulair. Singulair is widely used by asthmatics as a preventive for asthma attacks. Certain corticosteroids are employed for the same purpose. Neither montelukast nor the steroids are effective in terminating an established asthmatic attack. Beta agonists are employed for that purpose (see chapter 17). 

Beta agonists (terbutaline, albuterol) Theophylline Antidepressants Bupropion Citalopram Escitalopram Duloxetine Fluoxetine Fluvoxamine... 

Orciprenaline is a partially selective adrenoceptor-agonist and hence it is more likely to have effects on the cardiovascular system, such as arrhythmias, than the selective adrenoceptor-agonists, such as salbutamol, terbutaline and the long-acting beta-agonists salmeterol and formoterol. Orciprenaline is available only as tablets or syrup and can be prescribed to 4-year-old children. 

A failure to detect these classes of ADE may have serious consequences, as the ADE itself may be disabling or even life threatening, but even when it is relatively trivial it may be a reason for the patient s discontinuing effective treatment, which in turn may cause a deterioration in their condition. An example would be the patient who discontinues the treatment of his asthma with a beta-agonist because of tremor and then goes into status asthmaticus, with fatal consequences. 

Morbidity/Mortality - Regularly scheduled, daily use of beta agonists is not recommended. 

Exercise-induced bronchoconstriction Do not use montelukast as monotherapy. Patients should continue to use their usual regimen of inhaled beta-agonists as prophylaxis and have a short-acting inhaled beta-agonist available for rescue. 

Piletsky SA, Piletska EV, Chen B, Karim K, Weston D, Barrett G, Lowe P, Turner AP. Chemical grafting of molecularly imprinted homopolymers to the surface of microplates. Application of artificial adrenergic receptor in enzyme-linked assay for beta-agonists determination. Anal Chem 2000 72 4381-4385. 

Cates CJ, CriUy JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev 2006. 

Pharmacokinetics PO route onset rapid, peak 1-4 minutes, duration 15-75 minutes or 5 minutes if methacholine challenge is followed with a beta-agonist agent. Undergoes rapid hydrolysis in the plasma by acetylcholinesterase. 

Severe bronchoconstriction and reduction in respiratory function can result. Patients with severe hyperreactivity of the airways can experience bronchoconstriction at a dosage as low as 0.025 mg/ml (0.125 cumulative units). If severe bronchoconstriction occurs, reverse immediately by administration of a rapid-acting inhaled bronchodilator (beta-agonist). 

Previous trials with the beta-agonist salmeterol had given an average difference from placebo in PEF of 371/min while the effect of inhaled steroids was of the order of 251/min and A was chosen as a proportion of those effects. 

Typically, a mean improvement of 701/min would be seen following treatment with a short acting beta-agonist and A was chosen to be about 20 per cent of this. 

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