Antihistamines

Antihistamines are medications that counteract the effect of the natural chemical histamine.

Histamine is a vasoactive chemical. This means it has an effect on small blood vessels, resulting in dilated capillaries (redness), and leakage of protein-rich fluid into surrounding skin (swelling). Histamine affects nearby nerves resulting in itching. Histamine is stored in granules within mast cells together with other vasoactive chemicals.

Histamine release occurs in the following skin conditions:

• Insect bites
• Urticaria (hives), angioedema and anaphylaxis
• Dermographism
• Scombroid fish poisoning
• Urticaria pigmentosa.

There are at least two kinds of histamine receptors hence there are H1 and H2 blockers (antihistamines).

H1 blockers

Antihistamines are available for oral use as tablets and elixirs. They take about 15 to 30 minutes to be effective. There are short-acting medications (when several doses may be given in a day) or longer-acting for once-daily use. An injection can be given in case of severe allergic reaction (although in such cases, adrenaline (epinephrine) may be more appropriate and can be life-saving).

Topical preparations (ointments and creams) are often applied to insect bites but are not very effective as the antihistamine chemical does not penetrate the skin well.

Antihistamines are valuable drugs to reduce symptoms due to allergic diseases, especially those mediated by histamine. They do not always completely control the allergic reaction however, because they do not counteract other chemicals that may be responsible for the symptoms.

As the older type of antihistamines result in relaxation and help sleeping, they can be useful in other itchy skin diseases such as eczema, particularly taken at night. They are not thought to be addictive.

Other uses of antihistamines include:

• Sedation, for example before an operation
• Reduce nasal secretions in hay fever, or during a cold
• Counteract motion sickness
• Increase appetite, for example in those who are unwell.

Conventional antihistamines

Conventional antihistamines are obtainable in New Zealand without prescription. In September 2005 they include:

Short acting alkylamines

• Pheniramine (as eyedrops for allergic conjunctivitis)
• Chlorpheniramine/chlorphenamine (Histafen™, Demazin™; and several combination products marketed for upper respiratory tract infections)
• Dextrochlorpheniramine (Polaramine™, Polaramine Repetabs™).

Longer acting phenothiazines (these can help reduce nausea but can be quite sedating)

• Promethazine (Phenergan™)
• Trimeprazine or alimemazine (Vallergan™ Forte).

Ethanolamine

• Diphenhydramine (Unisom Sleepgels™; in combination Benadryl™ for cough, Panadol Night Caplet™ and others)

Propylamine derivatives

• Triprolidine, available in combination (Actifed™, Codral™ Daytime/Nighttime Tablets)

Piperazine

• Cyclizine (Marzine™), often used for travel sickness.

Others

• Azatadine (Zadine™)
• Hydroxyzine (Serecid™)
• Cyproheptadine (Periactin™), which also has antiserotonin effects (useful for migraine and to increase appetite).

The manufacturer's recommended dose should not be exceeded without medical advice, but in some patients, larger doses are necessary to control the skin condition.

Side effects include:

• Drowsiness
• Dry mouth, blurring of vision, difficulty passing urine and impotence (anticholinergic effects)
• Paradoxical stimulant effect (wakefulness and even agitation).

It is best not to drink alcohol when taking antihistamines, because this combination could result in excessive and potentially dangerous drowsiness.

Care needs to be taken with antihistamines when driving, flying or underwater diving.

Because they are broken down by the liver, those with liver disease are best to take a reduced dose as there will be excessive levels circulating in the blood stream.

In general, all drugs are best avoided in pregnancy, but there is no data to suggest that antihistamines are harmful to the mother or fetus so they are sometimes prescribed for severe urticaria in pregnant women. If a mother is breastfeeding, antihistamines may reduce milk production and could result in drowsiness of the infant, so are best avoided.

Antihistamine creams

• Mepyramine (Antisan™ cream), an ethylenediamine.

Unfortunately, antihistamine creams can occasionally cause contact allergic dermatitis so they should not be applied to large areas, and should be discontinued if they result in a rash. They should be avoided on broken skin.

Non-sedating antihistamines

Non-sedating antihistamines are much less likely to cause drowsiness.

Those available in New Zealand (September 2005) are:

• Loratadine (Claratyne™, Lora-Tabs™) and desloratadine (Claramax™)
• Cetirizine (Zyrtec™, Razene™)
• Fexofenadine (Telfast™).

Terfenadine (Teldane™) and astemisole (Hismanal™) have been withdrawn from the New Zealand market. These drugs may result in electrical disturbances in the heart resulting in palpitations and rarely sudden death when taken at the same time as the following medicines:

• Erythromycin (ERA™, EES™ )
• Ketoconazole (Nizoral™)
• Itraconazole (Sporanox™)
• Ciclosporin (Neoral™).

H2 blockers

A second type of histamine receptor (H2) is found in the stomach and skin. H2 blockers were developed to reduce stomach acid secretion and proved useful for patients with peptic ulcers. H2 blockers have also been found helpful for some patients with urticaria.

H2 blockers available in New Zealand include:

• Cimetidine (Cytine™)
• Ranitidine (Zantac™)
• Famotidine (Famox™, Pepzan™)

Side effects of H2 blockers are uncommon but include:

• Gastrointestinal upset (diarrhoea)
• Hair thinning
• Gynaecomastia (breast enlargement in males)
• Confusion or psychosis (in the elderly)
• Reversible impotence
• Blood count, liver, kidney, pancreatic disturbance (very rare)