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Table 8 Second-Line Medications for Anaphylaxis Treatment

From: World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis

Medication H1-Antihistaminesa (eg. Intravenous Chlorpheniramine or Diphenhydramine; Oral Cetirizine) Beta-2 Adrenergic Agonistsa (eg. Salbutamol [Albuterol] by Inhalation) Glucocorticoidsa (eg. Intravenous Hydrocortisone or Methylprednisolone; Oral Prednisone or Prednisolone)
Strength of recommendation for use in anaphylaxisb C C C
Pharmacologic effects At H1-receptor, inverse agonist effect; stabilize receptors in inactive conformation; decrease skin and mucosal symptoms At beta-2 receptor, increase bronchodilation Switch off transcription of activated genes that encode pro-inflammatory proteins; decrease late phase allergic response
Clinical relevance Decrease itch, flush, urticaria, sneezing, and rhinorrhea, but are not life-saving because they do not prevent or relieve obstruction to airflow or hypotension/shock Decrease wheeze, cough and shortness of breath but are not life-saving because they do not prevent or relieve upper airway obstruction or hypotension/shock Onset of action takes several hours; therefore, are not life-saving in initial hours of an anaphylactic episode; used to prevent and relieve protracted or biphasic anaphylaxis; however, these effects have not been proven
Potential adverse effects (usual dose) First-generation drugs cause drowsiness, somnolence, and impaired cognitive functionc Tremor, tachycardia, dizziness, jitteriness Unlikely during a short course
Potential adverse effects (overdose) Extreme drowsiness, confusion, coma, respiratory depression, and paradoxical central nervous system stimulation, eg. seizures in infants and children Headache, hypokalemia, vasodilation Unlikely
Comment From 0 to 14 different H1-antihistaminesc and different dose regimens are listed as adjunctive medications in anaphylaxis guidelines; role not proven Use in anaphylaxis is extrapolated from use in acute asthma; if given as adjunctive treatment for bronchospasm not relieved by epinephrine, should optimally be delivered by face mask and nebulization From 0 to 3 different glucocorticoidsd and different dose regimensd are listed as adjunctive medications in anaphylaxis guidelines; role not proven
  1. aH1-antihistamines, beta-2 adrenergic agonists, and glucocorticoids are considered to be second line (adjunctive or ancillary) medications relative to epinephrine, the first-line medication. There are no randomized placebo-controlled trials of any of these medications in the treatment of acute anaphylactic episodes.
  2. bLevels of evidence are defined as: A: directly based on meta-analysis of randomized controlled trials or evidence from at least one randomized controlled trial; B: directly based on at least one controlled study without randomization or one other type of quasi-experimental study, or extrapolated from such studies; C: directly based on evidence from non-experimental descriptive studies such as comparative studies, or extrapolated from randomized controlled trials or quasi-experimental studies.
  3. cH1-antihistamine use and dosing in anaphylaxis are extrapolated from urticaria treatment. The route of administration depends on the severity of the episode. Only first-generation H1-antihistamines are available for intravenous use. They potentially increase vasodilation and hypotension if given rapidly. If an oral H1-antihistamine is given, a low sedating medication such as cetirizine, which is available generically and absorbed rapidly, is preferable to a sedating H1-antihistamine such as chlorpheniramine or diphenhydramine.
  4. dGlucocorticoid use and dosing in anaphylaxis are extrapolated from acute asthma treatment. The route of administration depends on the severity of the episode.
  5. Adapted from references [2, 3, 15, 16, 2125, 3032, 121126].