antihistamines

Overview of Histamine

Histamine is a chemical messenger found in mast cells, playing a significant role in:

• Mediating allergic and inflammatory responses

• Stimulating gastric acid secretion

• Functioning as a neurotransmitter in the brain. Although histamine itself has no clinical applications, antihistamines that block its actions are therapeutically important.

Key Locations: High concentrations are found in the lungs, skin, blood vessels, and gastrointestinal tract, predominantly in mast cells and basophils, with some functions in the brain.

Synthesis and Release:

• Synthesis: Formed by the decarboxylation of histidine, facilitated by histidine decarboxylase. It is stored in mast cell granules, with rapid inactivation by amine oxidase if not stored.

• Release: Triggered by cell damage, toxins, insect venoms, and trauma. Allergies and anaphylaxis can cause significant histamine release.

Mechanism of Action: Histamine binds to receptors (H1, H2, H3, H4). H1 and H2 are clinically important:

• H1 effects: Smooth muscle contraction, increased capillary permeability, vasodilation.

• H2 effects: Stimulates gastric parietal cells, increasing acid secretion.

Role in Allergy and Anaphylaxis: Symptoms from histamine release mimic anaphylactic shock. Reactions can be localized (skin/respiratory) or systemic (anaphylaxis). Slow histamine release can cause localized reactions; rapid release can lead to anaphylaxis.

H1 Antihistamines Classifications:

• First generation: Older agents, cause sedation; examples include diphenhydramine, promethazine.

• Second generation: More selective for peripheral H1 receptors, causing less sedation; examples include cetirizine, loratadine.

Actions of H1 Antihistamines: Block histamine effects but do not prevent histamine formation or release. More effective in preventing symptoms than reversing them.

Therapeutic Uses:

• Allergic/Inflammatory Conditions: Effective for allergic reactions (e.g., allergic rhinitis) but not for bronchial asthma.

• Motion Sickness and Nausea: Agents like diphenhydramine are effective for travel-related symptoms.

• Somnifacients: First-generation antihistamines used occasionally for insomnia due to sedative properties.

Pharmacokinetics: Generally well absorbed orally; peak levels at 1-2 hours, with a plasma half-life of 4-6 hours. First-generation agents have widespread distribution, including CNS.

Adverse Effects:

• First-generation: Sedation, dizziness, potential anticholinergic effects (dry mouth, blurred vision).

• Second-generation: Minimal CNS effects; common adverse effect is headache.

Drug Interactions: May enhance effects of CNS depressants; contraindicated in patients on MAOIs.

Histamine H2-Receptor Blockers: Block histamine actions at H2 receptors, essential for reducing gastric acid secretion. Key drugs include cimetidine, ranitidine, famotidine, and nizatidine.