Anti-allergic Drugs

January 02 2006 Monday

Prescribing Notes

Antihistamines are indicated (1) to relieve itching, sneezing and rhinorrhoea of allergic rhinitis and hay fever, (2) in acute and chronic urticarias, (3) in acute mild allergic reactions and (4) i.v. as an adjunct to adrenaline in life-threatening anaphylaxis and angioneurotic oedema.

They are of no benefit in asthma. The most troublesome side effect is sedation, which is potentiated by other CNS depressants including alcohol. Sedation is so marked with alimemazine and promethazine that they are often used as sedatives in children. Promethazine is a potent antihistamine and is probably the drug of choice when both properties are required eg in the relief of nocturnal itch associated with urticaria.

Other side I effects of antihistamines can be traced; to their mild anticholinergic action (dry mouth, blurring of vision, constipation) and, in some, a-adrenergic blocking activity (impotence). In general, dose titration may be necessary to minimise 'side effects and achieve therapeutic success, and a trial of an alternative antihistamine from another chemical group may be necessary.

Non-Sedating Antihistamines

Sedation can largely be avoided using a non-sedating antihistamine such as cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine ormizolastine. Mizolastine has a weak potential to prolong the QT interval the degree of prolongation is modest and has not been associated with cardiac arrhythmias.

However, QT prolongation leading to life-threatening ventricular arrhythmias may occur due to elevated plasma levels of mizolastine in patients with hepatic impairment, or following drug interactions with liver enzyme inhibitors such as azole antifungals and macrolide antibiotics. It is contraindicated in such circumstances and it also must not be used with drugs known to prolong the QT interval.

Emollients and anti-pruritics

Prescribing Notes

Emollients are used to smooth the surface of the skin and to increase its degree of hydration. They act either by occluding water loss from the outer layer of skin, eg white soft paraffin, greasy emollients, emulsions and sprays - or by improving the binding of water to the skin, eg urea creams. Some patients experience a stinging sensation after application of a urea containing cream and also find their odour unpleasant. Stinging is reduced if preparations are applied to moist skin. Lanolin containing creams can cause allergic sensitisation unless rendered hypoallergenic by purification. Emollients can be added to the bath or used in the shower and are especially useful in atopic eczema and ichthyoses. Some may also be used as substitutes for soap. Sodium pyrrolidone carboxylate is a key constituent of the natural moisturising factor (NMF), which occurs in high concentrations in skin. It is a potent hygroscopic agent which is thought to repair, rehydrate and maintain the skin.

ECZEMA

A deficiency in cutaneous fatty acids is suspected as being implicated in the pathogenesis of atopic eczema, resulting in a defective immune system and impaired suppression of inflammatory responses. Topical application of the evening primrose extract, gamolenic acid, may help to correct the deficiency of this essential . fatty acid, thereby reducing the symptoms of atopic dermatitis such as irritation and dryness.

When applied topically, immunomodulators such as tacrolimus ointment inhibit calcium-dependent signal transduction in T-cells, thereby preventing the transcription and synthesis of interleukins and other cytokines involved in the inflammatory process. They have also been shown to inhibit the release of inflammatory mediators from mast cells, basophils and eosinophils. Pimecrolimus cream, a skin selective anti-inflammatory, has a similar mode of action with a low potential to impair local and systemic immunosurveillance. These agents have the advantage that they can be applied to delicate areas such as the face and neck, and do not cause the side effects commonly associated with topical steroids.

In infected eczema, emollients containing antibacterial agents such as benzalkonium chloride are effective against the causative bacterium Staphylococcus aureus.

PRURITIS

Antipruritics act by counter-irritation, and are applied topically. Crotamiton relieves itching, partly by production of erythema and a feeling of warmth.

Antihistamines block H1-receptors and reduce the swelling and irritation caused by the histamine that is released in response to injuries such as sunburn, insect stings and bits. Topical applications however may cause sensitisation and so antihistamines are best given orally, preferably as elixirs or syrups to increase their rate of absorption.

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