Beta-adrenergic agonists

Respiratory smooth-muscle cells contain the beta-2 subtype of adrenergic receptors.76 (See Chapter 18 for a discussion of adrenergic receptor classifications.) Stimulation of these beta-2 receptors results in relaxation of bronchiole smooth muscle. Lienee, drugs that stimulate these beta-2 adrenergic receptors (i.e., beta-adrenergic agonists) produce bronchodilation and can be used to prevent or inhibit airway obstruction in bronchospastic diseases.22,99 

Beta-adrenergic agonists are believed to induce smooth-muscle relaxation by the mechanism illustrat- 

FIGURE 26-1 Mechanism of action of beta agonists on respiratory smooth muscle. Beta agonists facilitate bronchodilation by stimulating adenyl cyclase activity, which in turn increases intracellular cyclic AMP production. Cyclic AMP activates protein kinase, which appears to add an inhibitory phosphate group to contractile proteins, thus causing muscle relaxation and bronchodilation. 

Beta-adrenergic drugs can be administered orally, subcutaneously, or by inhalation. Inhalation of these drugs is often the preferred method of administration in treating respiratory disorders. Inhalation allows the drug to be delivered directly to the respiratory tissues with a minimum of systemic side effects because of its absorption into the systemic circulation.4 The onset of action is also more rapid with inhalation. 

Drug Albuterol Primary Receptor Beta-2 Route of Administration Inhalation Oral Onset of Action (min) 5-15 15-30 Time to Peak Effect 1- 1.5 2- 3 Duration of Action (hr) 3-6 8 or more 

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Beta adrenergic agonists also exert bronchodilating effects. These drugs are thus often used in conjunction with theophiline in asthma therapy. A drug that combines both moieties, reproterol (40), has interestingly proved... 

Taylor DR, Sears MR. (1994) Regular beta-adrenergic agonists. Evidence, not reassurance, is what is needed. Chest. 106, 552-559. 

Drugs that may interact with labetalol include beta-adrenergic agonists, cimetidine, glutethimide, halothane, and nitroglycerin. 

Metaproterenol (Alupent, Metaprel) [Bronchodilator/Beta Adrenergic Agonist] Uses Asthma rev ible bronchospasm Action Sympathomimetic bronchodilator Dose AduUs. Inhal 1-3 inhal q3-4h, 12 inhal max/24 h wait 2 min between inhal PO 20 mg q6-8h Peds. Inhal 0.5 mg/kg/dose, 15 mg/dose max inhaled q4-6h by neb or 1-2 puffs q4-6h PO 0.3-0.5 mg/kg/dose... 

Alpha- and beta-adrenergic agonists epinephrine bitartrate epinephrine hydrochloride, racemic... 

Beta-adrenergic agonists, nonselecitve isoproterenol hydrochloride orciprenaline sulfate... 

Metaproterenol (Alupent, Metaprel) [Bronchodilator/ Beta-Adrenergic Agonist] Uses Asthma reversible bronchospasm Action Sympathomimetic bronchodilator Dose Adults. Neb 0.2-0.3 mL in 2.5-3.0 mL of NS Peds. Neb 0.1-0.2 mL/kg of a 5% soln in 2.5 mL NS Caution [C, /-] Contra Tach, other arrhythmias Disp Aerosol 0.65 mg/inhal soln for inhal 0.4, 0.6% tabs 10, 20 mg syrup 10 mg/5 mL SE Nervousness, tremors (common), tach, HTN Interactions T Effects W/ sympathomimetic drugs, xanthines T risk of arrhythmias W/ cardiac glycosides, halothane, levodopa, theophylline, thyroid hormones T HTN W/ MAOIs effects W/ BBs EMS Separate additional aerosol use by 5 min fewer 3i effects than isoproterenol longer-acting monitor lung sounds before/after administration... 

Goldstone, T.P., Duddridge, R. J., and Crompton, M., 1983, The activation of Na+-dependent efflux of Ca2+ from liver mitochondria by glucagon and beta-adrenergic agonists, Biochem. J. 210, pp. 463 172 Green, D.R. and Kroemer, G., 2004, The pathophysiology of mitochondrial cell death, Science 305, pp. 626-629... 

Chelmicka-Schorr E, Kwasniewski MN, Thomas BE, Amason BG (1989) The beta-adrenergic agonist isoproterenol suppresses experimental allergic encephalomyelitis in Lewis rats. J. Neuroimmunol. 25 203-207. 

Farmer P, Pugin J (2000) beta-adrenergic agonists exert their "anti-inflammatory" effects in monocytic cells through the IkappaB/NF-kappaB pathway. Am. J. Physiol. Lung Cell Mol. Physiol. 279 L675-682. 

Hetier E, Ayala J, Bousseau A, Prochiantz A (1991) Modulation of interleukin-1 and tumor necrosis factor expression by beta-adrenergic agonists in mouse ameboid microglial cells. Exp. Brain Res. 86 407-413. 

Severn A, Rapson NT, Hunter CA, Liew FY (1992) Regulation of tumor necrosis factor production by adrenaline and beta-adrenergic agonists. J. Immunol. 148 3441-3445. 

The cellular and molecular events involved in the dopamine-stimulated release of PTH can be clarified in experiments utilizing bovine parathyroid cells dispersed with collagenase and DNase (ft). This dispersion procedure yields parenchymal cells with only a slight contamination by red blood cells. The parenchymal cells exclude trypan blue and appear normal by light and electron microscopy (ft). These cells release PTH in a linear fashion for several hours the release is inhibited by calcium and stimulated by dopamine and beta-adrenergic agonists at concentrations comparable to those used to elicit physiological responses in vivo (ft,ft). 

The dopamine-stimulated formation of cAMP may initiate the dopamine-induced release of IR-PTH. A linear relationship exists between the dopamine-induced release of IR-PTH and the logarithm of the dopamine-induced accumulation of cAMP (17). Similarly, other agents increasing cAMP accumulation and IR-PTH release (e.g. beta-adrenergic agonists, secretin and phosphodiesterase inhibitors, also display such a log-linear relationship. Additional support for the possibility that intracellular cAMP might initiate PTH secretion comes from the observations that cholera toxin (JJ.), phosphodiesterase inhibitors (17) and dibutyryl cAMP (18), agents known to increase intracellular cAMP or mimic the biochemical effects of cAMP, increase the release of IR-PTH. 

Pure Gs that has been incorporated into phospholipid vesicles exhibits a very low GTPase activity, ranging from 0.02 to 0.05 mol hydrolyzed per min per mol of Gs [31], Co-incorporation into these vesicles of pure beta-adrenergic receptors increases this activity by a factor of 2-3 to 0.05-0.1 mol of GTP hydrolyzed per min per mol of Gs. Stimulation of the receptor with a beta-adrenergic agonist (isoproterenol) results in a further increase in GTP hydrolysis to rates of ca 1.0 mol of GTP hydrolyzed per min per mol of Gs [31,32],... 

M19. Mitra, S. P., and Carraway, R. E., Synergistic effects of neurotensin and beta-adrenergic agonist on 3,5-cyclic adenosine monophosphate accumulation and DNA synthesis in prostate cancer PC3 cells. Biochem. Pharmacol. 57, 1391-1397 (1999). 

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