Histamines and Antihistamines Synthesis Pharmacology Classification Drugs Brands

Histamine Pharmacology • Demonstrated to be a natural constituent of mammalian tissues (1927) • Involved in inflammatory and anaphylactic reactions. • Local application causes swelling redness, and edema, mimicking a mild inflammatory reaction. • Large systemic doses leads to profound vascular changes similar to those seen after shock or anaphylactic origin.

Histamine formation • Synthesized in mammalian tissues by decarboxylation of the amino acid l-histidine. • Histamines are stored in mast cells, skin, gastric and intestinal mucosa, lungs, liver and placenta, brain, epidermis, gastric mucosa etc.

Conditions That Release Histamine 1. Tissue injury 2. Allergic reactions 3. Drugs and other foreign compounds

Histamine receptors 1. H 1 receptors: mediate effects on smooth muscle leading to vasodilation, increased vascular permeability, and contraction of nonvascular smooth muscle. 2. H 2 receptors: mediate histamine stimulation of gastric acid secretion and may be involved in cardiac stimulation. 3. H 3 receptors: feedback inhibitors in CNS, gastrointestinal tract, lung, heart.

Pharmacological Effects: Exocrine Glands • • Gastric glands Salivary glands Sweat glands Pancreas Bronchial glands Lacrimal glands Secretion • All Secretions

Pharmacological Effects: Arterioles, Capillaries & Venules • Vasodilation • Increased permeability, (edema) • Systemic hypotension

Pharmacological Effects Vascular Smooth Muscles • Bronchial tree • Gastrointestinal tract • Uterus • Contraction

Antihistamines • Daniel Bovet, Nobel Prize 1944 Synthesized first antihistamines • Compounds appeared to prevent the binding of histamine to H 1 receptors through their structural similarities

General Mechanism of Action of Antihistamines • • Blocks action of histamine at receptor Competes with histamine for binding Displaces histamine from receptor Most beneficial when given early

Therapeutic Uses of H 1 Antihistamine Blockers 1. Allergic rhinitis, relieves rhinorrhea, sneezing, and itching of eyes and nasal mucosa. 2. Common cold: palliative, dries out the nasal mucosa. Often combined with nasal decongestant and analgesics. 3. Allergic dermatoses: can control itching associated with insect bites. 4. Outpatient procedures for preanesthetic sedation and prevention of nausea and vomiting 5. Antiemetic: prevention or treatment of nausea and vomiting 6. Hypnotics: limited value. 7. Other uses: a. Reduction of tremors and muscle rigidity in Parkinson's disease b. Treatment of migraine headaches

Classification of Antihistamines • First generation 1) Highly sedative. 2) Moderately sedative 3) Mild sedative • Second Generation /Non sedative antihistamines

First generation antihistamines • Highly sedative: - Drugs are Diphenhydramine, Dimenhydrinate, Promethazine, Hydroxyzine etc. Brands Diphenhydramine: -Amydramine, Histalix Stopkcough, Viscordil, Exylin etc. Dimenhydrinate: - Dizinil Promethazine: - Phenergan, Histazin Histaloc etc. Hydroxyzine: - Atarax

First generation antihistamines • Moderately sedative Drugs: - Pheniramine, Cyproheptidine, Meclizine, Cinnarizine etc. Brands: Pheniramine: - Avil Meclizine: - Longifene, Diligan Cinnarizine: - Stugeron Cyproheptidine: - Periactin Ketotifen: - Zaditen

First generation antihistamines • Mild sedatives Drugs: - Chlorpheniramine, Dexchlorpheniramine, Dimethindene, Triprolidine, Cyclizine, Clemastine etc. Brands: Chlorpheniramine: - Allerfin, Chlorhistol, Histop etc Dexchlorpheniramine: - Polaramine Dimethindene: - Fenistil Triprolidine: - Actifed, Sudafed, Sedofan etc. Clemastine: - Tavegyl

Second Generation /Non Sedative Antihistamines Drugs: - Fexofenadine, Loratidine, Desloratidine, Cetrizine, Levocetrizine, Azelastine, Mizolastine Ebastine, Rupatadine etc. Brands: Fexofenadine: - Telfast Loratidine: -Claritine, Restamine, Tidilor, clara, Lorine, etc Desloratidine: -Aerius Cetrizine: -Zyrtec, Zeran, Cetralon, Artiz, Alerid etc. Levocetrizine: - Xyzal

Thank You By, Philip K Mathew Clinical instructor University of Nizwa