Antihistamines (H1-receptor antagonists)

Key examples

• Cetirizine
• Loratadine
• Fexofenadine
• Chlorphenamine

 

Common indications

1. As a first-line treatment for allergies, particularly hay fever (seasonal allergic rhinitis).
2. To aid relief of itchiness (pruritus) and hives (urticaria) due, for example, to insect bites, infections (e.g. chickenpox) and drug allergies.
3. As an adjunctive treatment in anaphylaxis, after administration of adrenaline and other life-saving measures.
4. Other drugs in this class may be used for nausea and vomiting (see Antiemetics, histamine H1-receptor antagonists).

 

Mechanisms of action

• The term ‘antihistamine’ is generally used to mean an antagonist of the H1 receptor. H2-receptor antagonists have different uses and are discussed separately. Histamine is released from storage granules in mast cells as a result of antigen binding to IgE on the cell surface. Mainly via H1 receptors, histamine induces the features of immediate-type (type 1) hypersensitivity: increased capillary permeability causing oedema formation (wheal), vasodilatation causing erythema (flare), and itch due to sensory nerve stimulation. When histamine is released in the nasopharynx, as in hay fever, it causes nasal irritation, sneezing, rhinorrhoea, congestion, conjunctivitis and itch. In the skin, it causes urticaria. Widespread histamine release, as in anaphylaxis, produces generalised vasodilatation and vascular leakage, with consequent hypotension. Antihistamines work in these conditions by antagonism at the H1 receptor, blocking the effects of excess histamine. In anaphylaxis, their effect is too slow to be life-saving, so adrenaline is the more important first-line treatment.

 

Important adverse effects

• The ‘first-generation’ antihistamines (e.g. chlorphenamine) cause sedation. This because histamine, via H1 receptors, has a role in the brain in maintaining wakefulness. Newer ‘second-generation’ antihistamines (including loratadine, cetirizine and fexofenadine) do not cross the blood–brain barrier so tend not to have this effect. They have few adverse effects.

 

Warnings

• Commonly used antihistamines, including those mentioned above, are safe in most patients. Sedating antihistamines (e.g. chlorphenamine) should be avoided in severe liver disease, as they may precipitate hepatic encephalopathy.

 

Important interactions

• The antihistamines mentioned here are not subject to any major drug interactions.