INTRODUCTION TO HISTAMINE & HISTAMINE ANTAGONISTS

Introduction to Histamine and Histamine Antagonists

  • Chapter 74: Overview and critical review of histamine and its antagonists.

Overview of Histamine

  • Definition: Endogenous compound found in specialized cells throughout the body.

  • Roles:

    • Important in allergic reactions.

    • Regulation of gastric acid secretion.

    • Locally acting substance with varied effects.

  • Usage: Primarily restricted to diagnostic procedures.

  • Sources: Basophils, Respiratory system, GI tract.

Functions of Histamine

  • Receptors: Acts primarily on H1 and H2 receptors.

  • Systems Affected:

    • Vascular system (small blood vessels)

    • Bronchi

    • Central Nervous System (CNS)

    • Sensory nerves in nasal passages

    • Stomach

  • Pathologic States:

    • Allergic disorders

    • Peptic ulcer disease.

  • Physiological Effects:

    • Increases capillary permeability causing edema.

    • Bronchoconstriction leading to bronchospasms.

    • Modulates CNS functions impacting sleep-wake cycles and cognition.

    • Increases gastric motility and secretion.

Distribution, Synthesis & Storage of Histamine

  • Distribution:

    • Present in almost all tissues, most prevalent in skin, lungs, and GI tract.

    • Low plasma histamine content.

  • Synthesis & Storage:

    • Involves several peripheral cell types.

    • CNS production by neurons in the posterior hypothalamus with projections to the frontal and temporal cortices.

Release of Histamine

  • Allergic Release:

    • Mediates mild allergic reactions.

    • Initial requirement is the production of IgE antibodies in response to allergens.

    • IgE antibodies bind to mast cells and basophils.

    • Upon re-exposure, allergens bind to these antibodies, triggering the release of histamine.

    • Mechanism involves mobilizing intracellular calcium, causing histamine granules to fuse with cell membrane and release contents.

Mechanism of Allergy

  • Understanding allergenic reactions involving IgE, B-cells, and mast cells.

  • Graphical depiction of the immune response leading to allergy symptoms.

Nonallergic Release of Histamine

  • Causes:

    • Agents directly acting on mast cells.

    • Cell injury causing release.

    • Certain drugs and materials (e.g., radioactive contrast media).

    • No previous sensitization required.

Antihistamines Overview

  • Types:

    • H1 Receptor Antagonists (H1RA):

      • Selectively block H1 receptors.

      • Primarily treat mild allergic disorders; ineffective against colds.

    • H2 Receptor Antagonists (H2RA):

      • Block H2 receptors.

      • Treat gastric and duodenal ulcers.

H1 Receptor Antagonists (H1RA)

  • Actions:

    • Block actions of histamine-1 receptors.

    • Certain agents cause varied side effects due to blocking muscarinic receptors.

  • Generations:

    • First Generation: Produces significant sedation and anticholinergic effects; avoid alcohol and CNS depressants.

    • Second Generation: Minimal to no sedation and few anticholinergic effects.

Pharmacologic Effects of H1RA

  • Reductions:

    • Flushing, edema, itching, pain, and mucus secretion.

  • Additional Uses:

    • Insomnia (some agents may cause CNS depression).

    • Motion sickness treatment.

Nonsedative CNS Effects

  • Potential adverse effects of H1RAs includes:

    • Dizziness

    • Incoordination

    • Confusion

    • Paradoxical excitation (more common in children).

Acute Toxicity of H1RA

  • Symptoms (similar to atropine poisoning):

    • Dilated pupils, flushed face, hyperthermia, tachycardia, urinary retention.

    • CNS excitation, hallucinations, ataxia, and convulsions.

  • Management: Goals include removal of the drug and symptomatic relief.

Conclusion

  • End of Chapter 74: Summary of histamine, its functions and the implications of antihistamines.