• Clinical science

Antihistamines

Abstract

Histamine is a biologically active substance that potentiates the inflammatory and immune responses of the body, regulates physiological function in the gut, and acts as a neurotransmitter. Drugs that antagonize these effects by blocking or inhibiting histamine receptors (H receptors) are called antihistamines. Antihistamines are divided into two classes (H1 antihistamines and H2 antihistamines), based on the type of H receptor targeted. H1 antihistamines are mostly used to treat allergic reactions and mast cell-mediated disorders. This subtype is further divided into two generations. While the first-generation H1 antihistamines have a central effect and, thus, are also used as sedatives, second-generation H1 antihistamines have less central effects and are used primarily as antiallergenic drugs. H2 antihistamines are indicated primarily for gastric reflux disease because they reduce the production of stomach acid by reversibly blocking the H2 histamine receptors in the parietal cells of the gastric mucosa. Use of most H1 and H2 antihistamines is contraindicated during pregnancy and childhood. First-generation H1 antihistamines are specifically contraindicated in angle-closure glaucoma and pyloric stenosis.

Overview

Group Generation Drug Uses Characteristics
H1 antihistamines First
Second
  • Non-sedative/mildly sedative
H2 antihistamines
  • Usually used as a second-line treatment, or in combination with PPIs

References:[1][1][1][2][2][3][4]

H1 antihistamines

General physiology

  • Target: histamine H1 receptors
  • Location of H1 receptors
    • Smooth muscles (esp. bronchial and nasopharyngeal lining)
    • Vascular endothelial cell surfaces
    • Heart
    • Central nervous system
  • Effect of histamine on target
    • Capillary dilation and permeability → hypotension and edema
    • ↑ Bronchiolar smooth muscle contraction (via IP3 and DAG release) → bronchoconstriction
    • ↑ Nasal and bronchial mucus production
    • ↑ Activation of peripheral nociceptive receptorspain and pruritus
    • ↓ Conduction in AV node

Effects

  • Competitive, reversible antagonism of histamine H1 receptors
    • Inhibition of increased vascular permeability
    • Inhibition of allergic bronchial constriction
    • Central action: sedation

Side effects

Indications

Contraindications

[2]

H2 antihistamines

Target receptors

  • Target: histamine H2 receptors
  • Location of H2 receptors
  • Effect of histamine on target
    • ↑ Gastric acid secretion
    • Positive inotropism and automaticity
    • Smooth muscle relaxation → vasodilatation

Effects

  • Competitive, reversible antagonism of histamine H2 receptors → reduced production of stomach acid

Side effects

Indications

Contraindications

References:[2][5]