Antihistamines
Work in Progress Updated Feb 6, 2026
shakouri et al. 2013.
most common reaction to cetirizine - a second generation piperazine, followed by the parent drug hydroxyzine - a first generation piperazine (other derivative is levocetirizine)
piperadine = loratidine, fexofenadine
most common reaction reported with antihistamines = urticaria with or without angioedema
generally believed that an individual who is allergic to an antihistamine is unlikely to tolerate anothe preparation in the same class.
Benadryl liquid gels contain gelatin
skin testing has not been shown to be an optimal diagnostic.
challenge testing is the most definitive diagnostic procedure
simons et al JACI december 2011
what is the MOA of H1-antihistamines - inverse agonists (no antagonists or blockers) with immunoregulatory effects
histamine - synthesized from the amino acid histidine by L-histidine decarboxylase, expressed in many different cell types - 4 subtypes of receptors
Yanai et al pharmacology and therapuetics 2017
Histamine receptor = G protein-coupled receptor
ceterizine = a racemic combination of levocetirizine and dextrocetirizine
antihistamines act as inverse agonists on constitutively active H1 receptors, rednering activated histamine receptors inactive
while potency of antihsitamines differ (low = loratidne, fexofenadine; high = cetirizine, levocetirizine), clinical efficiacy as represented by maximum responsiveness is the same if administered in sufficient doses
second generation - high H1 receptor selectivity - low brain penetrability – due to the introduction of a hydrophilic functional group (-COOH or -NH2), less likely to pass the blood brain barrier and lower incidence of sedation –COOH is important because give a positive and negative charge in the same molecule, called “zwitter-ionic” compounds, which can explain poor blood brain barrier penetration. - long plasma half-life
first generation antihistamines - including hydroxyzine, diphenhydramine, and promethazine, developed between the 1940’s and 1970’s
fig 7 - classification of antihistamines by H1 receptor occupancy and sedating actions after single dose administration
middleton’s In Vivo Methods for the Study and Diagnosis of Allergy Antihistamines.
The H 1 antihistamines inhibit the wheal and flare response to histamine, allergen, and mast cell secretagogues. The duration of the inhibitory effect is linked to the pharmacokinetics of the drug and its active metabolites. First-generation H 1 antihistamines reduce skin reactivity for up to 24 hours or slightly longer. Ketotifen, another first-generation H 1 antihistamine, suppresses skin test responses for more than 5 days. The second-generation H 1 antihistamines azelastine, bilastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mizolastine, and rupatadine may suppress skin responses for 3 to 7 days.