Epinephrine is relatively contraindicated in diabetes mellitus because the drug can cause hyperglycemia due to increased glycogenolysis in the liver, decreased tissue uptake of glucose, and decreased insulin release from the pancreas. Systemic administration of epinephrine with other sympathomimetics may produce additive pharmacodynamic effects that increase the risk of developing adverse effects. Epinephrine is ineffective as a vasopressor for phenothiazine-induced hypotension and may worsen this condition. Epinephrine should not be used as a vasopressor for phenothiazine overdose. Halothane, cyclopropane, and other general anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines.
Cardiac glycosides can sensitize the myocardium to the actions of epinephrine.
Systemic administration of epinephrine to patients receiving cardiac glycosides may induce proarrythmias. Simultaneous use of epinephrine with oxytocics can cause severe, prolonged hypertension. Systemic administration of epinephrine may lead to generalized CNS stimulation manifested as fear, anxiety, nervousness, sleeplessness, excitability, psychomotor agitation, impaired memory, headache, and disorientation. These reactions can occur with therapeutic doses of systemic epinephrine. In patients with underlying psychiatric disturbances, epinephrine can induce more pronounced CNS effects including panic, hallucinations, aggressive behavior, and expression of suicidal or homicidal tendencies.