Antihistamines.ppt

Antihistamines Catherine Garrett Medicinal Chemistry Dr. Buynak Allergies Type I hypersensitivity Prevalence: 1 in 4 people 50 million Americans Sixth leading cause of chronic disease Healthcare system spends $18 billion a year Higher in urban areas The History of Allergies 1906- von Pirquet discovered tissue reactivity to external stimulants, called it “allergies” 1921- C. Prausnitz and H. Küstner found a connection between a serum factor, termed “reagine”, and allergies 1923- A.F. Coca and R. Cooke introduced the term atopy to define a “constitutional status of predisposition to develop allergic diseases as pollinosis and bronchial asthma with a reaginic pathogenesis.” 1945- Benadryl, first antihistamine introduced 1967- two American researchers discovered a “reaginic” factor with high reactivity that they named Immunoglobulin E 1981- Benadryl sold over the counter 1985- first non-sedating antihistamine introduced 1993- Claritin introduced 1996- Allegra and Zyrtec introduced Common Allergens Tree Pollen and Grass Pet Danders Mold Dust Mites Foods Symptoms Allergic Rhinitis Conjunctivitis Bronchoconstriction Urticaria Atopic Dermatitis Anaphylaxis /nasalsinus/allergicrhinitis.cfm Histamine Signal involved in local immune response, also a neurotransmitter synthesized by the decarboxylation of histidine Either stored or quickly inactivated by histamine-N-methyltransferase and diamine oxidase Release of histamine from mast cells is stimulated by IgE antibodies which respond to foreign antigens in the body Histamine Receptors H1 histamine receptor Found on smooth muscle, endothelium, and central nervous system tissue Activation results in vasodilatation, bronchoconstriction, smooth muscle activation, and separation of endothelial cells. H2 histamine receptor Found on parietal cells Regulates gastric acid secretion H3 histamine receptor Found in the central nervous system Regulates the release of other neurotransmitters H4 histamine receptor Recentl