Epinephrine has a narrow therapeutic window, reaching peak plasma levels in 5-10 minutes.17,40-44 Since it does not cross the blood-brain barrier, adverse reactions are the result of peripheral effects and may occur even with therapeutic doses. Signs and symptom may include restlessness, agitation, anxiety, tremulousness, headache, dizziness, pallor, palpitation, and tachycardia; and patients with Parkinson’s disease may experience increased tremor and rigidity.6-10,45-48
Particularly vulnerable populations to the effects of therapeutic doses of epinephrine include the young and the old; those with high BP, severe cardiovascular disease (i.e., unstable angina pectoris, recent myocardial infarction (MI), decompensated heart failure, severe valvular disease, supraventricular arrhythmias with uncontrolled ventricular rate, and symptomatic ventricular arrhythmias); patients with uncontrolled hyperthyroidism; and those taking certain drugs.6-10,45-48
Epinephrine should be used with caution in patients on other sympathomimetic agents because of additivity in patients on nonselective β-adrenoceptor antagonists, which block β2-adrenoceptor-mediated vasodilation resulting in unopposed α-adrenoceptor-induced vasoconstriction and high BP.17,45-50 Epinephrine should be avoided in patients on cocaine, since it inhibits the reuptake of epinephrine increasing HR and BP.50
Epinephrine should be used with caution in patients under the influence of general anesthetics (e.g., halothane and cyclopropane) that sensitize the myocardium to epinephrine causing ventricular arrhythmias (premature ventricular contractions, tachycardia, or fibrillation).17,45-50 Levonordefrin should be avoided in patients on tricyclic antidepressants (e.g., amitriptyline) that inhibit the reuptake of norepinephrine increasing HR.17,45-50
Epinephrine should be used with caution in patients with supraphysiological thyroid levels (i.e., thyroid overdose or hyperthyroidism) that upregulate β-adrenoceptors in vascular smooth muscles sensitizing the myocardium to β‑adrenergic effects of epinephrine increasing HR and BP.17,45-50 Caution is also recommended when patients are on digoxin and diuretics, which may increase cardiosensitivity and potentiate the arrhythmogenic effects of epinephrine, respectively.17
The β1-adrenergic activity of epinephrine may decrease uterine contraction and prolong labor; its α1-adrenergic activity may decrease uterine blood flow and fetal circulation. However, it has been shown that bolus doses of epinephrine, 0.1 mg, did not prolonged the duration of labor and did not adversely affect placental blood flow and fetal circulation.51-62 Investigators considered the addition of epinephrine to LAs beneficial for it reduced the dosage of LA required for pain relief.
Levonordefrin, in the mepivacaine 2% formulation, activates peripheral α2-adrenoceptors in vascular smooth muscles and causes vasoconstriction.49 It also activates α2-adrenoceptors in the cardiovascular control center of the CNS, thereby, suppresses sympathetic output from the brain and lowers BP. Consequently, levonordefrin is less likely than epinephrine to cause cardiac arrhythmias but it may cause reflex bradycardia.