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Epinephrine topical Side Effects

Applies to epinephrine topical: topical solution


Cardiovascular side effects have included elevations in heart rate or blood pressure in up to 55% and arrhythmias in 3% to 17% (including fatal ventricular arrhythmias) when used to treat cardiac arrest. In smaller doses, epinephrine has caused peripheral coronary arterial vasodilation, but in larger doses, epinephrine has caused diffuse vasoconstriction. This has caused increased peripheral vascular resistance, which was important in patients with coronary artery disease (worsened myocardial ischemia/angina) or hypertension (risk of emergent hypertension/stroke). Dilated cardiomyopathy and acute left ventricular dysfunction have been associated with the use of epinephrine.[Ref]

Epinephrine can induce hypokalemia with resultant T wave changes on the electrocardiogram.

Rare cases of myocardial infarction have been associated with relatively small doses of epinephrine in patients at risk for coronary artery disease.

Rare cases of cardiomyopathy have been associated with brief and chronic exposure to epinephrine (including inhaled epinephrine). Animal studies have shown that catecholamines can cause an influx of calcium into myocardial cells, which may cause myocardial injury, particularly during periods of epinephrine-induced coronary vasoconstriction. Limited animal data suggest that calcium antagonists may protect against the cardiotoxic effects of catecholamines by preventing the generation of plasma borne cytotoxic compounds, which are probably free radicals.

Epinephrine may be more arrhythmogenic in some patients, such as patients with congenital long QT syndrome.[Ref]

Nervous system

Nervous system side effects have included fear, agitation, anxiety, tenseness, restlessness, headache, tremor, dizziness, lightheadedness, nervousness, sleeplessness, excitability, weakness, and increased parkinsonian tremors. Complications associated with epidural anesthesia with epinephrine have included nerve root ischemia and clinical paralysis/plegia..[Ref]


Respiratory side effects have rarely included pulmonary edema. In some cases, acute left ventricular dysfunction has been documented in the presence of epinephrine-induced pulmonary edema. In some patients, epinephrine has precipitated severe, prolonged asthmatic attacks.[Ref]


Hypersensitivity side effects have been extremely unusual. Contact dermatitis has been associated with ocularly applied epinephrine. These reactions have typically presented with lid edema and a thick yellow discharge.[Ref]


Local side effects have included local tissue ischemia after repeated injections. Chronic IM epinephrine injections have induced local vasoconstriction, predisposing patients to Clostridial infections.[Ref]


Metabolic side effects have included severe metabolic acidosis because of elevated blood concentrations of lactic acid after prolonged use of intravenous epinephrine. Catecholamines have induced glycogenolysis, elevated blood glucose and insulin concentrations, and hypokalemia. Rare cases of hyperglycemia and acidosis have been associated with high catecholamine states, such as anaphylaxis.[Ref]


Psychiatric side effects have included agitation, disorientation, impaired memory, aggressive or assaultive behavior, hallucinations, and psychosis.[Ref]


Mattana and Singhal reviewed 420 consecutive cases of cardiac arrest and found a 28.6% incidence of acute renal failure (ARF) among patients who survived for at least 24 hours after cardiac arrest. Patients in whom ARF developed received markedly higher doses of epinephrine during resuscitative efforts than patients without ARF. High doses of epinephrine were associated with a longer duration of cardiopulmonary resuscitation. The patients with ARF had a significantly decreased survival rate. It is possible that patients with severe cardiac disease were less resuscitatable, required more epinephrine, and were prone to develop ARF anyway. Other data have failed to associated ARF with the use of high dose epinephrine.[Ref]

Renal side effects have included new or worsened renal insufficiency in adult survivors of cardiac arrest, adults who underwent epinephrine-assisted venography, and in rare pediatric cases.[Ref]


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2. Speer F, Tapay NJ "Syncope in children following epinephrine." Ann Allergy 28 (1970): 50-4

3. Piscatelli RL, Fox LM "Myocardial injury from epinephrine overdosage." Am J Cardiol 21 (1968): 735-7

4. Maguire WM, Reisdorff EJ, Smith D, Wiegenstein JG "Epinephrine-induced vasospasm reversed by phentolamine digital block." Am J Emerg Med 8 (1990): 46-7

5. Ferry DR, Henry RL, Kern MJ "Epinephrine-induced myocardial infarction in a patient with angiographically normal coronary arteries." Am Heart J 111 (1986): 1193-5

6. Tisdale JE, Patel RV, Webb Cr, Borzak S, Zarowitz BJ "Proarrhythmic effects of intravenous vasopressors." Ann Pharmacother 29 (1995): 269-81

7. McManus BM, Fleury TA, Roberts WC "Fatal catecholamine crisis in pheochromocytoma: curable cause of cardiac arrest." Am Heart J 102 (1981): 930-2

8. Kalsner S "High-dose epinephrine in cardiopulmonary resuscitation." N Engl J Med 328 (1993): 735

9. Fyfe AI, Daly PA, Dorian P, Tough J "Reversible "cardiomyopathy" after accidental adrenaline overdose." Am J Cardiol 67 (1991): 318-9

10. Taub SJ "Reactions to aerosol therapy." Eye Ear Nose Throat Mon 48 (1969): 653-4

11. Lansche RK "Systemic reactions to topical epinephrine and phenylephrine." Am J Ophthalmol 61 (1966): 95-8

12. Haft JI "Cardiovascular injury induced by sympathetic catecholamines." Prog Cardiovasc Dis 17 (1974): 73-86

13. Roy RC, Weeks DB "Otolaryngologists using local anesthetics containing epinephrine." Arch Otolaryngol 111 (1985): 280-1

14. Verrill PJ "Adverse reactions to local anaesthetics and vasoconstrictor drugs." Practitioner 214 (1975): 380-7

15. Whelan TV "Propranolol, epinephrine, and accelerated hypertension during hemodialysis." Ann Intern Med 106 (1987): 327

16. Ward CF "Otolaryngologists using local anesthetics containing epinephrine." Arch Otolaryngol 111 (1985): 281

17. "Product Information. Epinephrine Hydrochloride Injection (epinephrine)." Abbott Pharmaceutical, Abbott Park, IL.

18. Webster NR, Hinton W "Topical adrenaline." Anaesthesia 41 (1986): 435

19. Brummett RE "Warning to otolaryngologists using local anesthetics containing epinephrine. Potential serious reaction occurring in patients treated with beta-adrenergic receptor blockers." Arch Otolaryngol 110 (1984): 561

20. Clutter WE, Bier DM, Shah SD, Cryer PE "Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man." J Clin Invest 66 (1980): 94-101

21. "Product Information. Adrenalin Chloride Solution (epinephrine)." Parke-Davis, Morris Plains, NJ.

22. Hartman MM "Capabilities and limitations of major drug groups in allergy: their role within current theories." Ann Allergy 27 (1969): 164-81

23. Romaguera C, Grimalt F "Contact dermatitis from epinephrine." Contact Dermatitis 6 (1980): 364

24. Gibbs RC "Allergic contact dermatitis to epinephrine." Arch Dermatol 101 (1970): 92-4

25. Brown C, Martin D, Pepe P "High-dose epinephrine in cardiopulmonary resuscitation." N Engl J Med 328 (1993): 735-6

Not all side effects for epinephrine topical 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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