7.a. histamine & antihistaminics


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Third Year

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7.a. histamine & antihistaminics

  1. 1. Histamine & Antihistaminics Dr. fouzia nausheen
  2. 2. HISTAMINE • Histamine is a biologically active amine (autacoid & neurotransmitter in brain ) is Synthesized from the amino acid Histidine by decarboxylation • High amounts found in mast cells or basophils, lung, skin, & GIT & released by immunological mechanisms (Ag-Ab interaction ) →allergic response • Also occurs in venoms & in secretions from insect stings. Release of histamine • Stimuli causing the release of histamine from tissues include hypersensitivity reaction, cold, drugs(morphine), bacterial toxins, insect bite, trauma, etc. Mechanism of action : • Bind to 2 types of histamine receptors H1 & H2
  3. 3. Effects of histamine 1- CVS hypotension (vasodilatation), reflex tachycardia, flushing and feeling warm and headache Triple response (flush, flare “redness“ and wheal “local edema“) 2- Smooth muscles Bronchoconstriction and contraction of intestinal smooth muscles (diarrhea) 3- Nerve ending Stimulate sensory nerve endings, mediating pain and Itching 4. GIT-Stimulates gastric HCL secretion 5. It is released in anaphylactic reaction causing anaphylactic shock
  4. 4. Receptor Actions of Histamine H1 receptors located on nerve endings, smooth muscle & glandular cells. 1. Involved in inflammation & allergic reactions, 2. hypotension in anaphylaxis 3. Bronchoconstriction 4.  production of respiratory secretions 5. Abdominal cramps and diarrhea 6. Itching & pain by stimulating the sensory nerve endings. H2 receptors • Gastric acid secretion from the stomach.
  5. 5. Clinical uses of histamine Histamine aerosol has been used as in “Broncho-provocation test” in pulmonary function laboratories. It is done for patients with mild, atypical or non-specific symptoms of bronchial asthma. It is also done for occupational reasons. Agents used: histamine or methacholine. Histamine has no valid clinical use for any condition. Histamine analogue Betahistine used in the treatment of vertigo and meniers disease Adverse effects 1- flushing, ↓BP and ↑HR 2- headache 3- wheals 4- broncho-constriction and GI upset
  6. 6. Histamine antagonists 1. Physiologic antagonist Adrenaline has smooth muscle actions opposite to those of histamine, but they act at different receptors. Life saving in Anaphylactic shock which occurs due to massive release of histamine & other mediators. 2. Release Inhibitors- degranulation of mast cells triggered by IgE. Cromolyn & Nedocromil used in the treatment of asthma. 3. Histamine receptor antagonists Block the H1, H2 receptors
  7. 7. Antihistaminics- receptor antagonists H1 receptor blockers Competitive antagonists at H1 receptor First generation • Chlorpheniramine, Diphenhydramine, Doxylamine, Hydroxyzine, Promethazine , Cyproheptadine • Short to intermediate acting , • More sedating, more antimuscarinic side effects Second generation • Weak sedating - Cetrizine , Acrivastine, • Non sedating - Loratadine, Fexofenadine, • Longer duration of action, • Poor CNS entry (less lipid soluble) , least sedating, • No autonomic side effects.
  8. 8. Antihistaminics Uses : • Allergic reactions – Chlorphenaramine, Diphenhydramine Allergic rhinitis, conjunctivitis, pruritis (itching) angioneuritic oedema, urticaria . atopic dermatitis,and Anaphylaxis • Motion sickness - Diphenhydramine, • Antiemetic Prevention of nausea and vomiting in pregnancy – Promethazine, Doxylamine, • Drug induced parkinsonism - Diphenhydramine & Promethazine • Insect bite • Insomnia & anxiety for sedation Promethazine 2nd generation, less/non-sedating • Allergic rhinitis, urticaria, hay fever, pruritus - Loratadine, Cetrizine & Fexofenadine
  9. 9. Adverse effects : • CNS: sedation,  cognitive & psychomotor performance, appetite. • Anticholinergic – dry mouth, blurred vision, tachycardia, urinary retention & constipation • α adrenergic blockade-- Hypotension, reflex tachycardia • Additive effects with CNS depressants like benzodiazepines, barbiturates, MAO-Inhibitors & alcohol. Contraindicated in the treatment of individuals working in jobs where wakefulness is critical ( Drivers & Machine operators)
  10. 10. Second generation antihistamines Properties of second generation H1 antagonists include the following ---- 1.Have no anti cholinergic effect-------------- 2. Do not cross BBB hence no sedation 3. Do not impair psychomotor performance
  11. 11. H2 receptor blockers Cimetidine, Ranitidine, Famotidine, & Nizatidine • Inhibit gastric acid secretion Uses • Peptic ulcer, • Stress/Drug (e.g.NSAIDs) induced ulcers • Gastro Esophageal Reflux Disease, • Zollinger Ellison syndrome Drawbacks of Cimetidine • Antiandrogenic effects–(↑prolactin) gynaecomastia in males & galactorrhea in females • Confusion, agitation, & hallucination