Antihistaminics
Histamine
• physiologically active amine C5H9N3
• plant and animal tissue• Released from mast cells as part of an allergic
reaction (IgE / PG / LT / TNF-A / SP/ NKA Complement-mediated)
-Gastric Secretion-Capillary Dilatation-Bronchoconstriction-Hypotension Imidazoline
ring and amine gp
Synthesis
• Decarboxylation of AA Histidine by Histidine decarboxylase
• Mast cells and basophils
Mechanism of Action
• Combining with specific cellular receptors on cells viz H1-H4 ; Leucocyte diapedesis Neutrophil Chemotaxis Mast Cell Degranulation
• Primarily H1-mediated in Lewis’ Triple Response / UV
• H2-H4 blockers / Atypical Antihistaminics found largely ineffective
Type Location Function
H1 Found on smooth muscles, endothelium, and central nervous system tissue
Causes vasodilation, bronchoconstriction bronchial smooth muscle contraction, separation of endothelial cells (responsible for hives), and pain and itching due to insect stings; the primary receptors involved in allergic rhinitis symptoms and motion sickness; sleep regulation.
H2 Located on parietal cells Primarily stimulate gastric acid secretionAnd we use antiacidic drugs for this receptor
H3 Found on central nervous system and to a lesser extent peripheral nervous system tissue
Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin
H4 Found primarily in the basophils and in the bone marrow. It is also found onthymus, small intestine, spleen, andcolon.
Plays a role in chemotaxis.
1st Antihistaminic
• Piperoxan
• Discovered in 1933 by Jeff Forneau and Daniel Bovent while developing a guinea pig animal model of anaphylaxis
• They received the Nobel Prize in 1957
Antihistaminics
• Pharmaceutical agents that inhibit the action of histamine
• blocking its attachment to histamine receptors (Classic Antihistaminics)
• inhibiting the enzymatic activity of histidine decarboxylase (atypical antihistaminics)
• The term antihistamine only refers to H1 receptor antagonists
ClassificationH1 Blockers
Traditional Sedatives (esrt 1st Gen <1981)Low-Sedation agents (erst 2nd Gen)
H2 / H3 / H4-receptor Antagonists
Tricyclic Antihistaminics
Histidine Decarboxylase Enzyme-Inhibitors
Mast Cell Degranulation Inhibitors
• a
Traditional Sedative H1 blockers
• a
Low-Sedation H1 Blockers
• aa
H2 Receptor Antagonists
• Parietal Cells – Inhibit Gastric Secretion
• Cimetidine• Ranitidine• Nizatidine• Roxatidine• Famotidine• Lafutidine
H3 Receptor Antagonists
• Nootropics / Neuromodulators
• Ciproxifan• Clobenpropit• Conessine
H4 Receptor Antagonists
• Immunomodulators
• Thioperamide• VUF-6002• JNJ 7777120
Histidine Decarboxylase Inhibitors
• Tritoqualine• Catechin
Mast Cell Degranulation Inhibitors
• Sodium Cromogylcate• Nedocromil
• Inhalational Agents ; Ineffective in Cutaneous Dermatoses
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