Autacoids 2 Histamine Histamine is a bio amine

Autacoids: 2 - Histamine • Histamine is a bio amine derived principally from dietary histidine which is decarboxylated by L- histidine decarboxylase. • Histamine is synthesized through the body but is highly concentrated in the granules of basophils and mast cells. Physiological functions of histamine 1. Allergic responses 2. Cell proliferation and cell differentiation 3. Hematopoiesis. 4. Neurotransmitter related to wakefulness and memory

• One approach to manage the effect of histamine is to inhibit histamine release from mast cells. • Cromolyn (intranasal, ophthalmic, inhalation), mast cell stabilizer used for treatment of allergic rhinitis, allergic conjunctivitis, and asthma. • Other ophthalmic mast cell stabilizers (iodoxamide, nedocromil, pemirolast). • Adverse effects of the mast cell stabilizers are generally related to the route of administration and includes burning or irritation of the tissues. • Histamine receptors H 1, H 2, H 3, H 4 (G protein coupled receptors)

The H 1 receptor • Mediate typical allergic and anaphylactic responses to histamine release such as bronchoconstriction, vasodilation, increased capillary permeability and spasmodic contraction of GI smooth muscles. • H 1 antagonists • Block the physiological response to histamine release and so act as symptomatic relief of allergic symptoms (Seasonal rhinitis and conjunctivitis) or the common cold caused by rhinovirus infections. • Symptomatic relief of urticaria • Because of some anticholinergic activities, some H 1 receptor antagonist can be used as antiemetics and anxiolytics

First generation H 1 receptor antagonists Group Drug Effect • ethanolami nes Clemastine, diphenhydramine, doxylamine. • Diphenhydramine have mild antiemetic effect diphenhydramine, doxylamine have sedating effect. Brompheniramine, chloropheniramine, alkylamines dexpromopheniramine, dexchloropheniramine. piperazine hydroxyzine piperidine cyproheptadine phenothiazi promethazine ne Mild anxiolytic antiemetic Many of the first-generation agents are significantly sedating and have anticholinergic activities

Second generation H 1 receptor antagonists. Group Drug piperazines Cetirizine, levocetirizine piperidines Loratadine, desloratadine and fexophenadine Less or non sedating due to limited ability to cross BBB.

• Many ophthalmic and intranasal preparations for allergic rhinitis and allergic conjunctivitis. • Adverse effects of H 1 receptor antagonists are relatively minor and so anti histaminics are available as over the counter preparations. • Common adverse effects includes CNS effects including sedation fatigue hallucination and ataxia mostly observed in first generation. • Anti cholinergic effects as dry mouth, urinary retention and constipation. • The second generation are relatively free of side effects.

The H 2 receptor Mediate production of gastric acid secretions. • The H 2 receptor antagonist Competitively block h 2 receptor and so limiting the effect of histamine on gastric acid secretion. • Used to treat gastric hyper secretory conditions such as gastric and duodenal ulcers. • OTC preparations are indicated for heart burn, (Cimetidine, ranitidine, famotidine and nizatidine). • Adverse effects CNS AE (confusion, dizziness), hepatic or renal dysfunction. Cimetidine have androgenic effects with high doses (impotence, and gynecomastia) and it’s a significant inhibitor of CYP 450 leading to potential for serious drug – drug interaction.