Histamine and serotonin
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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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Histamine and serotonin

Histamine and Serotonin

By

S.Bohlooli, PhD

Ardabil University of Medical Sciences


Basic pharmacology of histamine

Basic pharmacology of histamine

Chemistry

Pharmacokinetics

Pharmacodynamics

Ardabil University of Medical Sciences


Distribution

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


Chemistry and pharmacokinetics

Chemistry and pharmacokinetics

Ardabil University of Medical Sciences


Metabolism

Metabolism

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Storage and release

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


Pharmacodynamics

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


Histamine and serotonin

Ardabil University of Medical Sciences


Nervous system

Nervous system

  • regulation of drinking

  • body temperature

  • secretion of antidiuretic hormone

  • control of blood pressure

  • perception of pain

  • wakefulness

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Cardiovascular system

Cardiovascular System

  • Vasodilation

  • Increased "Capillary" Permeability

  • Triple Response of Lewis

  • Heart

  • Histamine Shock

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Extravascular smooth muscle

Extravascular Smooth Muscle

  • Contraction is due to activation of H1 receptors

  • relaxation (for the most part) is due to activation of H2 receptors

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Exocrine glands

Exocrine Glands

  • regulator of gastric acid secretion

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Peripheral nerve endings

Peripheral Nerve Endings

  • Pain

  • Itch

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Clinical pharmacology of histamine

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


Histamine antagonists

Histamine antagonists

  • H1 receptor antagonists

  • H2 receptor antagonists

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Basic pharmacology of h 1 receptor antagonists

Basic Pharmacology of H1 Receptor Antagonists

Chemistry

Pharmacokinetics

Pharmacodynamics

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Chemistry

Chemistry

  • Structure-activity Relationship

    • reversible competitive inhibitors

    • contain a substituted ethylamine moiety

Ardabil University of Medical Sciences


Histamine and serotonin

Ardabil University of Medical Sciences


Pharmacokinetics

Pharmacokinetics

  • Absorption, distribution

  • Metabolism:

    • Astemizole and Terfenadine

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Pharmacological properties

Pharmacological Properties

  • Smooth Muscle

  • Capillary Permeability

  • Flare and Itch

  • Immediate Hypersensitivity Reactions

  • Central Nervous System

    • Can both stimulate and depress the CNS

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Pharmacodynamics1

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

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Clinical pharmacology of h 1 receptor antagonists

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


Histamine and serotonin

Ardabil University of Medical Sciences


Histamine and serotonin

Ardabil University of Medical Sciences


Histamine and serotonin

Ardabil University of Medical Sciences


Application common cold

Application:Common Cold?

  • Despite persistent popular belief, H1 antagonists are without value in combating the common cold.

Ardabil University of Medical Sciences


Basic pharmacology of serotonin

Basic pharmacology of serotonin

Chemistry

Pharmacokinetics

Pharmacodynamics

Ardabil University of Medical Sciences


Chemistry pharmacokinetics

Chemistry & pharmacokinetics

Ardabil University of Medical Sciences


Histamine and serotonin

Ardabil University of Medical Sciences


Pharmacodynamics2

Mechanism of action

Tissue and organ system effect

Nervous system

Airways

Cardiovascular system

Gastrointestinal tract

Skeletal muscle

Pharmacodynamics

Ardabil University of Medical Sciences


Histamine and serotonin

Ardabil University of Medical Sciences


Histamine and serotonin

Ardabil University of Medical Sciences


Clinical pharmacology of serotonin

Clinical pharmacology of Serotonin

  • Serotonin agonists

  • Serotonin antagonists

Ardabil University of Medical Sciences


Histamine and serotonin

Ardabil University of Medical Sciences


Serotonin antagonists

Serotonin antagonists

  • Phenoxybenzamine (5HT2)

  • Cyproheptadine (5HT2)

  • Ketanserin (5HT1C)

  • Odansetrone (5HT3)

Ardabil University of Medical Sciences


Appetite control through serotonin

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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