38. HISTAMINES AND ANTIHISTAMINICS

Introduction

Histamine is a chemical messenger naturally present in many tissues such as skin, lungs, stomach and blood vessels. It is stored mainly in mast cells and plays an important role in allergic reactions, inflammation, gastric acid secretion and neurotransmission. Antihistamines are drugs that block the effects of histamine and are widely used in allergic conditions.

Histamine: Formation and Storage

Histamine is formed by the decarboxylation of the amino acid histidine. It is stored in mast cell granules in tissues like skin, bronchial mucosa, liver and placenta. When triggered by allergens, drugs or injury, mast cells release histamine, leading to symptoms such as itching, redness, swelling and bronchoconstriction.

Mechanism of Action of Histamine

Histamine works by binding to different receptors in the body:

  • H1 receptors: Involved in allergic reactions, bronchoconstriction, vasodilation and increased capillary permeability.
  • H2 receptors: Increase gastric acid secretion in the stomach.
  • H3 and H4 receptors: Present in the nervous and immune system (less clinically important).

Histamine Liberators

Certain agents can cause release of histamine from mast cells without immune activation. Examples include opiates, radiographic contrast media and some muscle relaxants.

Clinical Use of Histamine

Histamine has no major clinical use. An exception is betahistine, a histamine analogue used orally for vertigo in Meniere’s disease. It improves blood flow in the inner ear. Side effects include nausea, headache and itching. It should be avoided in peptic ulcer and asthma.

Antihistamines (H1-Receptor Antagonists)

H1-antihistamines block the H1 receptors and prevent the actions of histamine. They are widely used in allergies, motion sickness and as sedatives.

Classification of H1-Antihistamines

First-Generation (Sedating)

  • Promethazine
  • Diphenhydramine
  • Chlorpheniramine
  • Dimenhydrinate
  • Cinnarizine

Second-Generation (Non-Sedating)

  • Loratadine
  • Desloratadine
  • Cetirizine
  • Levocetirizine
  • Fexofenadine
  • Azelastine (nasal spray/eye drops)

Mechanism of Action of H1 Blockers

These drugs act as competitive antagonists at H1 receptors. They reduce the allergic symptoms caused by histamine such as itching, swelling and redness. First-generation drugs also cross the blood–brain barrier, producing sedation and anticholinergic effects.

Pharmacological Actions of First-Generation Antihistamines

  • CNS depression: Sedation, drowsiness and impaired concentration.
  • Antiallergic action: Relieves symptoms of type-I hypersensitivity reactions.
  • Anticholinergic effects: Dry mouth, blurred vision, constipation and urinary retention.
  • Antiemetic action: Useful in motion sickness due to vestibular suppression.
  • Local anaesthetic effect: Mild numbing action.

Adverse Effects of First-Generation Antihistamines

  • Drowsiness and lack of focus
  • Headache and fatigue
  • Dry mouth and urinary retention (anticholinergic effects)
  • Nausea, vomiting and gastric discomfort
  • Rarely, allergic reactions or dermatitis

Uses of First-Generation Antihistamines

  • Allergic diseases: Urticaria, rhinitis, conjunctivitis, dermatitis, angioedema.
  • Common cold: Provide symptomatic relief through anticholinergic and sedative effects.
  • Pre-anaesthetic medication: Promethazine for sedation and prevention of nausea.
  • Motion sickness: Dimenhydrinate and diphenhydramine.
  • Parkinsonism: Promethazine and diphenhydramine reduce tremors.
  • Vertigo: Cinnarizine and meclizine are effective in Meniere’s disease.
  • Adjunct in anaphylaxis: Combined with adrenaline for supportive therapy.

Second-Generation Antihistamines

These drugs selectively block H1 receptors without significant CNS penetration, therefore cause minimal or no sedation.

Properties

  • No anticholinergic effects
  • Do not cause sedation or impair psychomotor function
  • Longer duration of action
  • Better safety profile

Uses

  • Allergic rhinitis (e.g., cetirizine, fexofenadine, loratadine)
  • Urticaria and eczema
  • Allergic conjunctivitis (azelastine or levocabastine eye drops)

Antivertigo Drugs

Vertigo is a spinning sensation caused by problems in the inner ear or brain. Drugs used include:

  • Cinnarizine, promethazine, diphenhydramine (H1-blockers)
  • Hyoscine (anticholinergic)
  • Prochlorperazine (phenothiazine)
  • Betahistine (H1-analogue)
  • Diuretics (acetazolamide, thiazides)
  • Diazepam, tricyclic antidepressants, corticosteroids

Cinnarizine reduces calcium entry into vestibular cells and helps control vertigo.

Detailed Notes:

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