Respiratory - Antihistamines (H1 - Receptor antagonists

Question 1

Antihistamines

Indications?

Answer 1

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

Question 2

Antihistamines

Mode of Action?

Answer 2

• 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

Question 3

Antihistamines

Adverse Effects?

Answer 3

• 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.

Question 4

Antihistamines

Warnings/Important interactions

Answer 4

• 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.

Question 5

Antihistamines

Practical Prescribing?

Answer 5

• Cetirizine (10 mg tablets), loratadine (10 mg tablets) and chlorphenamine (4 mg tablets and 2 mg/5 mL oral solution) may be purchased without prescription.
• Cetirizine and loratadine are taken orally on a once daily basis.
• Chlorphenamine is taken orally every 4–6 hours. In anaphylaxis, chlorphenamine 10 mg IV or IM may be administered, but this must not be prioritised over adrenaline and other life-saving measures (e.g. fluid resuscitation).