Antihistamine
The vast majority of marketed H-antihistamines are receptor antagonists and only a minority of marketed compounds are inverse agonists at the receptor. Clinically, H-antihistamines are used to treat allergic reactions and mast cell-related disorders. Sedation is a common side effect of H-antihistamines that readily cross the blood–brain barrier; some of these drugs, such as diphenhydramine and doxylamine, are therefore used to treat insomnia. H-antihistamines can also reduce inflammation, since the expression of NF-κB, the transcription factor the regulates inflammatory processes, is promoted by both the receptor's constitutive activity and agonist (i.e., histamine) binding at the H receptor.
Angioedema
In allergic angioedema, avoidance of the allergen and use of antihistamines may prevent future attacks. Cetirizine is a commonly prescribed antihistamine for angioedema. Some patients have reported success with the combination of a nightly low dose of cetirizine to moderate the frequency and severity of attacks, followed by a much higher dose when an attack does appear. Severe angioedema cases may require desensitization to the putative allergen, as mortality can occur. Chronic cases require steroid therapy, which generally leads to a good response. In cases where allergic attack is progressing towards airway obstruction, epinephrine may be life-saving.