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 AUTACOIDS ƒ a.k.a. Dz‘ ƒŽŠ‘”‘‡•dz ƒ endogenous substances with biological activity. ƒ not released or stored in glands. ƒ not circulated in blood. ƒ are formed at the site of action. ƒ produce localized action.  Classification of Autacoids 1. Biologically active ami...

 AUTACOIDS ƒ a.k.a. Dz‘ ƒŽŠ‘”‘‡•dz ƒ endogenous substances with biological activity. ƒ not released or stored in glands. ƒ not circulated in blood. ƒ are formed at the site of action. ƒ produce localized action.  Classification of Autacoids 1. Biologically active amines 9Histamine 9Serotonin  Classification of Autacoids 2. Lipid derived autacoids ( Eicosanoids) 9Prostaglandins 9Leukotrienes 9Thromboxanes 3. Ergot Alkaloids 9a small molecule produced by decarboxylation of the amino acid histidine 9 itis catalyzed by the enzyme L-histidine decarboxylase in a reaction that requires pyridoxal phosphate. o Histamine is found in many tissues, including the brain. o it is stored and found in the highest amounts in mast cells and basophils.  Two processes by which HISTAMINE IS RELEASED 1. Energy- and Ca2+-dependent degranulation reaction. 2. Energy- and Ca2+ - independent release (displacement). Storage & Release: 1.Energy- and Ca2+-dependent degranulation reaction. Immunologic Release o Mast cells, if sensitized by surface IgE antibodies, degranulate when exposed to specific antigen. o Histamine released by this mechanism is a mediator of in immediate (type I) allergic reactions. o This type of release requires energy and calcium. 2. Energy- and Ca2+ - independent release (displacement). Chemical & Mechanical Release o Occurs following chemical or mechanical injury to mast cells. o Displacement is induced by drugs such morphine, tubocurarine, guanethidine, and amine antibiotics. o This type of release does not require energy and is not associated with mast cell injury or degranulation. ƒ Histamine ƒ R-alpha methylhistamine is an H3-specific agonist. ƒ Betazole (histalog) ƒ tenfold greater activity at H2-receptors than at H1- receptors ƒ Impromidine ƒ investigational agent; its ratio of H2:H1 activity is about 10,000 o Flushing o Hypotension o Tachycardia o Headache o Wheals o Bronchoconstriction o Gastrointestinal upset o Aka : ANTIHISTAMINES o competitive inhibitors at the H1- receptor. 1. 1st Generation Antihistamines a. Ethanolamines: Carbonoxamine, Dimenhydrinate, Diphenhydramine, Doxylamine, Clemastine b. Ethylaminediamines: Pyrilamine, Tripelennamine c. Piperazine: Hydroxyzine, Cyclizine, Meclizine d. Alkylamines: BACphen Brompheniramine, Chlorpheniramine e. Phenothiazines: Promethazine f. Miscellaneous: Cyproheptadine ‰Piperidines ‰Miscellaneous agents o Terfenadine (Seldane) o metabolized to the active metabolite fexofenadine by a specific cytochrome P- 450. o Loratadine (Claritin). 9 Poor CNS penetration. o Cetirizine (Zyrtec) 9 not associated with cardiac abnormalities. 9 has poor penetration into the CNS. 9 less sedating; it is ineffective for motion sickness or antiemesis. A. well absorbed after oral administration. o Normal effects seen in 30 minutes (with maximal effects at 1-2 hours) o The duration of action is : ‰ 1ST generation compounds: 3-6 hours ‰ 2ND generation compounds: 3-24 hours o Treatment of allergic rhinitis and conjunctivitis. 9 treat the common cold based on their anticholinergic properties o Treatment of urticaria and atopic dermatitis, including hives o Sedatives 9Several (doxylamine, diphenhydramine) are marketed as over-the-counter (OTC) sleep aids. o Prevention of motion sickness o Appetite suppressants o sedation (synergistic w/ alcohol, other depressants, dizziness, and loss of appetite. CAUTION: drivers and machine operators o gastrointestinal upset, nausea, constipation and diarrhea. o anticholinergic effects (dry mouth, blurred vision, and urine retention). (1) Histamine (H2)-receptor antagonists include 9 Cimetidine (Tagamet) 9 Ranitidine (Zantac) 9 Famotidine (Pepcid AC) 9 Nizatidine (Axid) (2) competitive antagonists at the H2- receptor, which predominates in the gastric parietal cell. USE/S: ƒ treatment of gastrointestinal disorders: ¥ heartburn and acid-induced indigestion ¥ promote the healing of gastric and duodenal ulcers ¥ hypersecretory states such as Zollinger-Ellison syndrome Cimetidine, ranitidine, and famotidine 9 undergo first-pass hepatic metabolism resulting in a bioavailability of approximately 50%. 9 Nizatidine has little first-pass metabolism and a bioavailability of almost 100%. o inhibits binding of dihydrotestosterone to androgen receptors o (anti-ANDROGEN) o men= gynecomastia or impotence o inhibits metabolism of estradiol, and increases serum prolactin levels. o women= galactorrhea Cimetidine o Potent ENZYME INHIBITOR o interferes with several important hepatic cytochrome P450 drug metabolism pathways, including those catalyzed by CYP1A2, CYP2C9, CYP2D6, and CYP3A4 9cromolyn (Intal) 9nedocromil sodium (Tilade) 1. poorly absorbed salts; ROUTE of admin: inhalation 2. They inhibit the release of histamine and other autacoids from the mast cell. 3. Prophylactic agents in asthma