Antihistamines

An antihistamine is a drug which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions, through action at the histamine receptor. Only agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines – other agents may have antihistaminergic action but are not true antihistamines.

In common use, the term antihistamine refers only to H₁-receptor antagonists, also known as H₁-antihistamines. It has been discovered that these H₁-antihistamines are actually inverse agonists at the histamine H₁-receptor, rather than antagonists per se. (Leurs, Church & Taglialatela, 2002)

Pharmacology

In allergic reactions an allergen (a type of antigen) interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors.

Histamine, acting on H₁-receptors, produces pruritus, vasodilatation, hypotension, flushing, headache, tachycardia, bronchoconstriction, increases vascular permeability, potentiates pain, and more. (Simons, 2004)

While H₁-antihistamines ameliorate these effects, they are only efficacious if administered prior to the allergen-challenge. In severe allergies, such as anaphylaxis or angioedema, these effects may be so severe as to be life-threatening. Epinephrine, often in the form of an autoinjector (Epi-pen), is required by people with such hypersensitivities.

References

Forneau E, Bovet D (1933). Recherches sur l’action sympathicolytique d’un nouveau derive du dioxane. Arch Int Pharmacodyn 46, 178-91.
Leurs R, Church MK, Taglialatela M (2002). “H₁-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects”. Clin Exp Allergy 32 (4): 489-98. PMID 11972592.
Nelson, WL (2002). In Williams DA, Lemke TL (Eds.). Foye’s Principles of Medicinal Chemistry (5 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 0-683-30737-1
Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2
Simons FE (2004, Nov 18). “Advances in H₁-antihistamines”. N Engl J Med 351 (21): 2203-17. PMID 15548781.