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Moderate Beta- 2 adrenergic bronchodilators (Includes salmeterol) ↔ cardiovascular Moderate Potential Hazard, Moderate plausibility. Applies to: Hyperthyroidism, Heart Disease, Hypertension Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression). Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol. However, beta-2-selectivity is not absolute and can be lost with larger doses. High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias. Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and/or underlying cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, or hypertension.

The recommended dosages should not be exceeded. References • 'Product Information. Brethaire (terbutaline).'

Novartis Pharmaceuticals, East Hanover, NJ. • Tranfa CME, Pelaia G, Grembiale RD, Naty S, Durante S, Borrello G 'Short-term cardiovascular effects of salmeterol.' Chest 113 (1998): 1272-6 • Price AH, Clissold SP 'Salbutamol in the 1980s. A reappraisal of its clinical efficacy.' Drugs 38 (1989): 77-122 • Richards DM, Brogden RN 'Pirbuterol. A preliminary review of its pharmacological properties and therapeutic efficacy in reversible bronchospastic disease.'

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Drugs 30 (1985): 6-21 • Maguire GP, Emirgil C 'Bronchodilator and side effects of different modes of administration of metaproterenol: inhaled, oral, and in combination.' Am J Med Sci 291 (1986): 168-74 • Finch JS 'Cardiovascular toxicity: clinical evaluation of albuterol, isoproterenol and placebo in rising dose tolerance trial.'

Ann Allergy 47 (1981): 402-4 • Chodosh S, Crooks LA, Tuck J 'Comparative effects of pirbuterol acetate, metaproterenol, and placebo aerosols on pulmonary function and incidence of cardiac ectopy.' J Asthma 26 (1989): 309-15 • Hibbard JU 'Chronic terbutaline therapy and peripartum cardiomyopathy: a case-control study.' Hypertens Pregnancy 15 (1996): 183-91 • Spitzer WO, Suissa S, Ernst P, Horwitz RI, Habbick B, Cockcroft D, Boivin JF, McNutt M, Buist AS, Rebuck AS 'The use of beta-agonists and the risk of death and near death from asthma.' N Engl J Med 326 (1992): 501-6 • 'Adverse effects and complications of treatment with beta-adrenergic agonist drugs.

Committee on drugs, the American Academy of Allergy and Immunology.' J Allergy Clin Immunol 75 (1985): 443-9 • Bierman CW, Kemp JP, Nathan RA 'Efficacy and safety of inhaled bitolterol mesylate via metered-dose inhaler in children with asthma.' Ann Allergy Asthma Immunol 76 (1996): 27-35 • 'Product Information. Severent (salmeterol).' Glaxo Wellcome, Research Triangle Park, NC. • Maconochie JG, Forster JK 'Dose-response study with high-dose inhaled salmeterol in healthy subjects.' Br J Clin Pharmacol 33 (1992): 342-5 • Larsson S 'Long-term treatment with beta2-adrenostimulants in asthma.