Intramuscular (IM) adrenaline should be considered in the initial management when anaphylaxis is diagnosed, or strongly suspected, or when intravenous (IV) access is not established. It should be injected at mid-anterolateral thigh in a dose of 0.01 mg/kg of 1:1,000 (1 mg/ml) solution, to a maximum of 0.5 mg in adults (0.3 mg in children). The dose can be repeated every 5–15 min depending on the response and the severity of anaphylaxis.

When IV access is established and in the presence of close hemodynamic monitoring, adrenaline 1:10,000 (0.1 mg/ml) can be administered intravenously in small doses, titrating to effect (50 mcg (0.5 ml) boluses in adults, 1 mcg/kg in children).

Serious adverse effects such as hypertensive crises, ventricular arrhythmias and pulmonary edema can occur after an overdose of adrenaline. Groups of patients who are at higher risk in the event of overdose include patients at the extremes of age and patients with ischemic heart disease, hypertension or hyperthyroidism. Cocaine and amphetamines sensitize the myocardium to the effects of adrenaline. In contrast, beta blockers and angiotensin converting enzyme inhibitors can decrease the effectiveness of endogenous and exogenous catecholamines.

H1-antihistamines are a second-line medication for anaphylaxis and should not be a substitute for adrenaline. In Cochrane systematic review, the administration of H1-antihistamine in anaphylaxis was not supported by evidence from randomized controlled trials.

Examples of H1-antihistamines are IV Chlorpheniramine (10–20 mg in adults; 0.2 mg/kg in children) or IV diphenhydramine (10–50 mg in adults; 5 mg/kg/24 h in children). H1-antihistamines exert their pharmacologic effects at H1-receptors with inverse agonist effect and stabilize receptors in an inactive conformation. Compared to adrenaline, H1-antihistamines have slow onset of action.

H1-antihistamines are useful for symptomatic treatment of flushing, urticaria, pruritus, sneezing and rhinorrhea but are not life-saving as they have little effect on bronchospasm and hypotension.

First-generation H1-antihistamines can cause somnolence and impaired cognitive function with the usual dosage. In the event of overdosage, they can cause extreme drowsiness, coma, respiratory depression and seizures in infants and children.