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Histamine and Serotonin

Histamine and Serotonin. By S.Bohlooli, PhD. Basic pharmacology of histamine. Chemistry Pharmacokinetics Pharmacodynamics. Distribution. Histamine is widely, if unevenly, distributed throughout the animal kingdom and is present in many venoms, bacteria, and plants.

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Histamine and Serotonin

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  1. Histamine and Serotonin By S.Bohlooli, PhD Ardabil University of Medical Sciences

  2. Basic pharmacology of histamine Chemistry Pharmacokinetics Pharmacodynamics Ardabil University of Medical Sciences

  3. Distribution Histamine is widely, if unevenly, distributed throughout the animal kingdom and is present in many venoms, bacteria, and plants. Ardabil University of Medical Sciences

  4. Chemistry and pharmacokinetics Ardabil University of Medical Sciences

  5. Metabolism Ardabil University of Medical Sciences

  6. Storage and release • Immunologic release • histamine plays a central role in immediate hypersensitivity and allergic responses • The release of histamine only partially explains the biological effects that ensue from immediate hypersensitivity reactions • Chemical and mechanical release • Tubocurarine, succinylcholine, morphine Ardabil University of Medical Sciences

  7. Pharmacodynamics • Mechanism of action • Tissue and organ system effect • Nervous system • Cardiovascular system • Bronchial smooth muscle • Gastrointestinal tract smooth muscle • Other smooth muscle organs • Secretary tissue • Metabolic effects • The triple response • Other effects possibly mediated by histamine Ardabil University of Medical Sciences

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  9. Nervous system • regulation of drinking • body temperature • secretion of antidiuretic hormone • control of blood pressure • perception of pain • wakefulness Ardabil University of Medical Sciences

  10. Cardiovascular System • Vasodilation • Increased "Capillary" Permeability • Triple Response of Lewis • Heart • Histamine Shock Ardabil University of Medical Sciences

  11. Extravascular Smooth Muscle • Contraction is due to activation of H1 receptors • relaxation (for the most part) is due to activation of H2 receptors Ardabil University of Medical Sciences

  12. Exocrine Glands • regulator of gastric acid secretion Ardabil University of Medical Sciences

  13. Peripheral Nerve Endings • Pain • Itch Ardabil University of Medical Sciences

  14. Clinical pharmacology of histamine • Clinical use • a diagnostic agent • to assess nonspecific bronchial hyperreactivity in asthmatics • as a positive control injection during allergy skin testing • Toxicity and contraindications • Flushing, hypotension,tachycardia, headache wheals, brochoconstriction, gastrointestinal upset Ardabil University of Medical Sciences

  15. Histamine antagonists • H1 receptor antagonists • H2 receptor antagonists Ardabil University of Medical Sciences

  16. Basic Pharmacology of H1 Receptor Antagonists Chemistry Pharmacokinetics Pharmacodynamics Ardabil University of Medical Sciences

  17. Chemistry • Structure-activity Relationship • reversible competitive inhibitors • contain a substituted ethylamine moiety Ardabil University of Medical Sciences

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  19. Pharmacokinetics • Absorption, distribution • Metabolism: • Astemizole and Terfenadine Ardabil University of Medical Sciences

  20. Pharmacological Properties • Smooth Muscle • Capillary Permeability • Flare and Itch • Immediate Hypersensitivity Reactions • Central Nervous System • Can both stimulate and depress the CNS Ardabil University of Medical Sciences

  21. Pharmacodynamics • Histamine receptor blockade • Other actions • Sedation • Antinausea and antiemetic actions • Antiparkinsonism effects • Antichlinoceptor effect: Promethazine • Adrenoceptor blocking action • Serotonin blocking action • Local anesthesia: Promethazine Ardabil University of Medical Sciences

  22. Clinical pharmacology of H1 receptor antagonists • Clinical use • Allergic reaction • Motion sickness and vestibular disturbance • Nausea and vomiting of pregnancy? • Toxicity • Sedation, antimuscarninc action, • Drug allergy • Drug interaction • Teratogenic effects Ardabil University of Medical Sciences

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  26. Application:Common Cold? • Despite persistent popular belief, H1 antagonists are without value in combating the common cold. Ardabil University of Medical Sciences

  27. Basic pharmacology of serotonin Chemistry Pharmacokinetics Pharmacodynamics Ardabil University of Medical Sciences

  28. Chemistry & pharmacokinetics Ardabil University of Medical Sciences

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  30. Mechanism of action Tissue and organ system effect Nervous system Airways Cardiovascular system Gastrointestinal tract Skeletal muscle Pharmacodynamics Ardabil University of Medical Sciences

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  33. Clinical pharmacology of Serotonin • Serotonin agonists • Serotonin antagonists Ardabil University of Medical Sciences

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  35. Serotonin antagonists • Phenoxybenzamine (5HT2) • Cyproheptadine (5HT2) • Ketanserin (5HT1C) • Odansetrone (5HT3) Ardabil University of Medical Sciences

  36. Appetite control through serotonin? • Sertonin related to sleep, emotion, sex, and appetite • Could reduce food intake • Fenfluramine, dexfenfluramine • Cause serotonin release and inhibition of food uptake • Toxicity: • fatal and nonfatal pulmonary hypertension • Valvular lesions Ardabil University of Medical Sciences

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