H-1 ANTAGONISTS

• H1 antagonists, also known as H1 blockers or antihistamines, are a class of drugs that inhibit the action of histamine at the H1 receptor sites.

• They are widely used to treat various allergic conditions and are classified into three main categories:

1. First-Generation H-1 Antagonists

2.Second-Generation H-1 Antagonists

3. Mast Cell Stabilizers

Medical Uses of H-1 Antagonists

• Allergic Rhinitis: Reduces symptoms like sneezing and nasal congestion.

• Allergic Conjunctivitis: Alleviates itching and redness in the eyes.

• Urticaria: Treats hives and skin rashes.

• Angioedema: Reduces swelling beneath the skin.

• Pruritus: Relieves itching from atopic dermatitis and insect bites.

• Nausea and Vomiting: Some antihistamines have antiemetic properties.

• Sedation: First-generation antihistamines are used as sleep aids due to their sedative effects.

Side Effects

• Sedation and Drowsiness (especially with first-generation agents)

• Blurred Vision

• Dry Mouth

• Constipation or Diarrhea

• Nausea and Vomiting

• Increased Appetite and Weight Gain

• Anxiety or Insomnia

• Dry Cough

Classification

1. First-Generation H1 Antagonists

Characteristics:

i) Sedative Effects: Easily cross the blood-brain barrier, causing drowsiness.

ii) Anticholinergic Activity: Block muscarinic acetylcholine receptors, leading to side effects like dry mouth and blurred vision.

iii) Affordable and Widely Available: Oldest class of antihistamines.

Mechanism of Action:

i) Histamine Blockade: Competitively inhibit histamine binding at H1 receptors.

ii) G-Protein Coupled Receptor Inhibition: Prevent activation of phospholipase C, reducing inositol phosphate (IP₃) and diacylglycerol (DAG) formation.

iii) Reduced Intracellular Calcium: Decreases the release of inflammatory mediators.

Functions:

i) Decrease Vascular Permeability: Reduces edema and swelling.

ii) Alleviate Pain and Headache: Minimizes discomfort associated with allergies.

iii) Prevent Hypotension: Stabilizes blood pressure by inhibiting vasodilation

2. Second-Generation H1 Antagonists

Characteristics:

i) Non-Sedative: Less likely to cross the blood-brain barrier, resulting in minimal sedation.

ii) Selective Action: More specific to peripheral H1 receptors.

iii) Hydrophilic Nature: Limits central nervous system penetration.

Mechanism of Action:

Similar to first-generation antihistamines but without significant central nervous system effects.

Functions:

i) Alleviate Allergy Symptoms: Effective in treating allergic rhinitis, conjunctivitis, and urticaria without causing drowsiness.

3. Mast Cell Stabilizers

Characteristics:

i) Prevent Histamine Release: Stabilize mast cell membranes, inhibiting degranulation.

ii) Anti-Inflammatory Activity: Reduce the release of other inflammatory mediators.

Mechanism of Action:

i) Calcium Channel Blockade: Inhibit IgE-mediated calcium influx into mast cells.

ii) Prevent Degranulation: Without intracellular calcium, histamine vesicles cannot fuse with the cell membrane.