Isoproterenol Side Effects
For the Consumer
Applies to isoproterenol: parenteral injection
Side effects include:
Nervousness, headache, dizziness, restlessness, insomnia, anxiety, tension, blurring of vision, fear, excitement, tachycardia, palpitations, angina, Adam-Stokes syndrome, pulmonary edema, hypertension, hypotension, ventricular arrhythmias, tachyarrhythmias, flushing of the skin, diaphoresis, mild tremors, weakness.
For Healthcare Professionals
Applies to isoproterenol: compounding powder, inhalation aerosol, inhalation aerosol with adapter, inhalation solution, intravenous solution
A 43-year-old man with normal coronary arteries developed reproducible chest pain, ST segment ECG changes, and ventricular tachycardia during an isoproterenol infusion, indicating isoproterenol-induced coronary artery vasospasm and arrhythmia. The man was successfully treated with diltiazem and isosorbide dinitrate.
A 51-year-old man status post cardiac transplant, with syncope upon standing, was found to have decreased right middle cerebral blood flow and decreased systolic blood pressure during a formal tilt test with isoproterenol. The authors believe that cerebral hypoperfusion in a patient with a denervated heart may be due to a combined effect of upright tilt and a direct vasomotor response of the middle cerebral artery to isoproterenol.
Catecholamines, in general, are associated with some types of ventricular tachycardia. Several cases of syncope or near syncope in patients with no structural cardiac disease, with ventricular tachycardia induced only by isoproterenol or exercise are reported.
In some patients who have died after prolonged treatment with high doses of some catecholamines, such as norepinephrine, or in some patients with high levels of endogenous catecholamines, such as pheochromocytoma, autopsy has revealed diffuse myocardial inflammation and necrosis consistent with direct myocardial toxicity. Prolonged exposure to high doses of catecholamines can also cause medial necrosis and destruction of the elastic lamellae of large blood vessels.[Ref]
Cardiovascular side effects have been significant. As a beta-adrenergic agonist, isoproterenol has caused tachycardia and palpitations, life-threatening ventricular arrhythmias, enhanced AV nodal conduction, enhanced myocardial contractility, and peripheral vasodilation. Some patients complained of chest tightness.
Due to an increase in the cardiac work and oxygen demand to oxygen supply ratio in some patients (particularly patients with coronary artery disease) during isoproterenol therapy, rare cases of myocardial ischemia and infarction are reported.
In some patients, presumably with organic disease of the AV node, isoproterenol injection has caused or worsened AV heart block. Cases of Adams-Stokes attacks are reported.[Ref]
Rare cases of paradoxical bronchospasm have been reported. Paradoxical bronchospasm may be due to a local irritative effect of inhaled isoproterenol on sensitive bronchial mucosa, a counteractive effect of a metabolite of isoproterenol, 3-methoxyisoproterenol, which is a weak beta-adrenergic antagonist, or an irritating effect of an inert inhalant are reported.[Ref]
Respiratory side effects have included throat irritation and rare cases of paradoxical bronchospasm. Other problems accompany excessive use of isoproterenol. In a select group of patients with refractory asthma who use progressively greater amounts of isoproterenol with less and less effectiveness, a vicious cycle, or "locked lung" syndrome develops, which may indicate severe underlying disease rather than toxicity of isoproterenol.[Ref]
Nervous system side effects have included nervousness or jitteriness, headache, dizziness, and tremors.[Ref]
Musculoskeletal side effects have included inhibition of myometrial contractility.[Ref]
Hypersensitivity side effects have included rare cases of severe pharyngeal and true vocal cord edema and erythema.[Ref]
A 48-year-old man with reactive airways disease developed pharyngeal and true vocal cord edema and erythema within 2 days after starting an isoproterenol metered dose inhaler. Skin patch testing revealed sensitivity to pure isoproterenol hydrochloride. No complement-fixing antibody was demonstrated.[Ref]
Metabolic side effects have included rare reports of decreased serum potassium.[Ref]
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2. Mann DE, Marmont P, Shultz J, Reiter MJ "Atrioventricular nodal reentrant tachycardia initiated by catecholamine-induced ventricular tachycardia. A case report." J Electrocardiol 24 (1991): 191-5
3. Njemanze PC "Isoproterenol induced cerebral hypoperfusion in a heart transplant recipient." Pacing Clin Electrophysiol 16 (1993): 491-5
4. Winsor T, Wright RW, Berger HJ "Isoproterenol toxicity." Am Heart J 89 (1975): 814-7
5. Jones SE, Epstein AE "Variant angina provoked by isoproterenol: an unusual cause of syncope." Am Heart J 116 (1988): 1628-30
6. Castellanos A, Mendoza IJ, Luceri RM, Castillo CA, Zaman L, Saoudi N, Myerburg RJ "Concealment of manifest, and exposure of concealed, ventricular parasystole produced by isoproterenol." Am J Cardiol 55 (1985): 1344-9
7. Finch JS "Cardiovascular toxicity: clinical evaluation of albuterol, isoproterenol and placebo in rising dose tolerance trial." Ann Allergy 47 (1981): 402-4
8. Winsor T, Mills B, Winbury MM, Howe BB, Berger HJ "Intramyocardial diversion of coronary blood flow: effects of isoproterenol-induced subendocardial ischemia." Microvasc Res 9 (1975): 261-78
9. Light RW, Taylor RW, George RB "Albuterol and isoproterenol in bronchial asthma. Efficacy and toxicity of drugs administered via intermittent positive pressure breathing." Arch Intern Med 139 (1979): 639-43
10. "Product Information. Isuprel (isoproterenol)." Sanofi Winthrop Pharmaceuticals, New York, NY.
11. Windom HH, Burgess CD, Siebers RW, Purdie G, Pearce N, Crane J, Beasley R "The pulmonary and extrapulmonary effects of inhaled beta-agonists in patients with asthma." Clin Pharmacol Ther 48 (1990): 296-301
12. Price DE "Isoprenaline--kill or cure?" Med Sci Law 7 (1967): 215-6
13. Berger HJ, Winsor R "Letter: Isoproterenol and electrocardiographic findings." Ann Intern Med 84 (1976): 221-1
14. Brandon ML "Long-term study comparing fenoterol and isoproterenol inhalation in asthmatic patients." Ann Allergy 40 (1978): 86-93
15. Haft JI "Cardiovascular injury induced by sympathetic catecholamines." Prog Cardiovasc Dis 17 (1974): 73-86
16. Vlay SC "Catecholamine-sensitive ventricular tachycardia." Am Heart J 114 (1987): 455-61
17. Gavrilescu S "Manifestation of the Wolff-Parkinson-White syndrome during isoprenaline infusion and carotid sinus massage." Cardiology 61 (1976): 146-9
18. Page R, Gay W, Friday G, Fireman P "Isoproterenol-associated myocardial dysfunction during status asthmaticus." Ann Allergy 57 (1986): 402-4, 429-30
19. Spector S "Tolerance to beta-adrenergics and results of rising dose studies of albuterol, isoproterenol and placebo." Ann Allergy 47 (1981): 394-401
20. Van Metre TE, Jr "Adverse effects of inhalation of excessive amounts of nebulized isoproterenol in status asthmaticus." J Allergy 43 (1969): 101-13
21. Trautlein J, Allegra J, Field J, Gillin M "Paradoxic bronchospasm after inhalation of isoptroterenol." Chest 70 (1976): 711-4
22. Ke R, Vohra M, Casper R "Prolonged inhibition of human myometrial contractility by intermittent isoproterenol." Am J Obstet Gynecol 149 (1984): 841-4
23. Warth J, Rappaport A "Atypical reaction to isoproterenol." JAMA 209 (1969): 417
Not all side effects for isoproterenol may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.
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