Medications for Allergy

• describe the pathophysiology of allergic rhinitis;

• outline the causes of allergic rhinitis;

• explain why antihistamines may be contraindicated in asthmatic patients;

• describe alternatives to antihistamines in treating allergic rhinitis.

Part 1

It’s that time of year when 14-year-old Dean’s symptoms trouble him most. He suffers from excessive sneezing, rhinorrhoea and nasal congestion. These symptoms make him very irritable, he cannot sleep properly, feels very fatigued and as a result is less focused on his school work. Since some important school exams are due to begin soon, his mother insists that Dean sees a doctor. His doctor prescribes azelastine hydrochloride. Before writing the prescription, the doctor checked Dean’s medical notes and questioned him to make sure that he did not suffer from asthma.

What is the likely diagnosis of Dean’s symptoms?

Allergic rhinitis.

What is allergic rhinitis and what are the causative factors?

Perennial and seasonal allergic rhinitis affects many individuals and can cause serious complications, such as otitis media and chronic sinusitis. The symptoms of allergic rhinitis can be caused by house dust mites, pollens, moulds and other allergens.

Comment on the pathophysiology of this condition.

A type 1 hypersensitivity reaction is responsible for the development of the allergy. The symptoms are due to the effects of mast cell degranulation with the release of histamine. Mast cells are located in the nasal passages and the nasal mucosa is sensitive to the effects of histamine released from these cells, leading to inflammation of the mucous membranes of the nose. The inflammation is associated with oedema and swelling, vasodilation and an increase in the secretion of mucus. The mucous membrane of other sections of the respiratory tract (accessory sinuses, nasopharynx, and upper and lower respiratory tract) will also be affected by the allergic reaction.

What category of drugs can be used for perennial allergic rhinitis?

Perennial allergic rhinitis can be treated with antihistamines and corticosteroids.

To which category of drugs does azelastine hydrochloride belong?

Azelastine hydrochloride is an antihistamine, an H1 receptor antagonist which is available as a nasal spray.

Why is it important that Dean’s doctor checks whether he suffers from asthma?

Antihistamines should be used with caution in patients with asthma. This is due to a reduction in expectoration following the drying effect of the drugs, which may thicken the bronchial and bronchiolar secretions.

Part 2

After a couple of weeks Dean returned to his doctor, complaining that his symptoms were persistent.

Is there an alternative medication for Dean’s persistent symptoms?

An alternative medication could be the use of topical nasal corticosteroids, such as beclometasone or budesonide, administered as a nasal spray: cromoglicate may also be used. The mechanism of cromoglicate is poorly understood; it may stabilize the mast cells to reduce degranulation and histamine release. It is useful in the prophylaxis of both asthma and allergic rhinitis. The topical antihistamines are less effective than topical corticosteroids, but more effective than cromoglicate. Cromoglicate, however, is the first choice in children < 12 years of age.

Key Points

• Perennial and seasonal allergic rhinitis are type 1 hypersensitivity reactions to an allergen.

• The symptoms are due to the effects of mast cell degranulation. The effects can cause serious complications, such as otitis media and chronic sinusitis.

• Allergens which cause these symptoms include house dust mites, pollens and moulds.

• Treatment of allergic rhinitis includes antihistamines, H1 receptor antagonists, such as axelastine, and corticosteroids, such as beclometasone or budesonide. However, cromoglicate is the first choice for children.

Second-generation antihistamines

The newer antihistamines are devoid of anticholinergic and sedative effects with the exception of cetirizine, which may be mildly sedating in some patients. The low incidence of side effects is attributed to their high selectivity for peripheral H1-receptors and low propensity to cross the blood-brain barrier. Three 2nd-generation antihista-mines for oral administration are currently available in the United States: cetirizine, fexofenadine, and loratadine. All appear effective in mitigating the symptoms of allergic rhinitis. Table 2 lists available agents and dosages.

Table 2 Second-generation antihistamines

Cardiotoxicity associated with astemizole and terfenadine is the most serious side effect associated with the 2nd-generation antihistamines. Serum accumulation of these agents may deleteriously prolong the QT interval. Serious ventricular arrhythmias (including Torsades de pointes), cardiac arrest, and death have ensued as a result of overdoses and concomitant use of medications that impair the metabolism of terfenadine and astemizole (potent inhibitors of cytochrome P450 3A4 isoenzymes, such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, indinavir, fluoxamine). These reactions and interactions have not been associated with the currently available agents. (Both terfenadine and astemizole have since been voluntarily withdrawn from the US market; terfenadine has been replaced with its nonarrhythmogenic metabolite, fexofenadine.)

Azelastine is a new topically administered 2nd-generation antihistamine that has demonstrated efficacy in improving both early- and late-phase symptoms of allergic rhinitis. Symptomatic response may be seen as early as 30 minutes after dose. In comparative trials, intranasal azelastine appears equally as efficacious as oral antihistamines but generally less effective than corticosteroids in relieving nasal symptoms. The most commonly reported adverse effects are bitter taste, application site irritation, and somnolence. Azelastine is administered 2 sprays per nostril twice daily.

It is well-known that people in certain parts of the planet are far more likely to suffer from allergic rhinitis than in other parts, though it is not so clear why that happens. In Denmark, just over one in every 100 visits to a family physician involves seasonal allergic rhinitis, though in Britain the figure is one in 50 and in Australia almost one in 10. The disease is more of an urban than a rural phenomenon, a fact which has led many researchers to point a finger at air pollution as an aggravating condition.

Air pollution may indeed play a role in the increased incidence of this condition, perhaps because gases such as ozone and nitrous oxide are harming epithelial cells, the bloodless surface covering of human tissues, glands, and organs. But one study suggested that the role of air pollution may have been exaggerated. The children of Leipzig, despite breathing the notoriously polluted and sulfur dioxide-laden air of former East Germany, were found to have lower rates of rhinitis than children in the western, alpine city of Munich.

Physicians and rhinologists have traditionally divided allergic patients into those whose symptoms were seasonal and those who suffered all year round. Yet a single patient with a number of seasonal reactions to allergens that peak at different times of year may appear to have a year-round allergy. In any case, an individual with severe perennial symptoms should receive different drug treatments from an individual with mild seasonal symptoms.

For the person who suffers moderate, occasional allergic rhinitis symptoms, there are a variety of pharmacological allies available. Allergen avoidance is, as always, the ideal solution, but it may prove practically impossible for allergy sufferers who have no choice but to share the air they breathe with allergenic pollen. It helps, however, to know when the pollen count of a particular allergenic plant is going to begin climbing, and when it will peak, in order to begin therapy beforehand.

Treatment may include the use of non-sedating oral antihistamines, or topical antihistamines or so-called mast cell stabilizers to the nose and eyes. Mast cells act as receptors for the allergenic pollen, and for the antibody immunoglobulin E which the body uses to defend itself. Its reaction to these signals is to release substances such as histamine that worsen rhinitis symptoms.

Oral antihistamines, which are used to prevent this histamine reaction, offer a number of alternatives in terms of speed of onset and duration of effect for the treatment of milder seasonal rhinitis, available under names such as terfenadine, cetirizine (Zyrtec), astemizole (Hismanal) and acrivastine (Semprex). Topical antihistamines such as levocabastine (Livostin) and azelastine (Astelin), however, are becoming more widely used because their effect can be concentrated on the most affected organ. Topical sodium cromoglycate, long used in treatment of allergic rhinitis symptoms, still has a place today because the absence of significant side effects permits regular use without worry.

Those who suffer from more severe forms of seasonal allergic rhinitis should be treated according to whether they are primarily eye sufferers or primarily nose sufferers. If their symptoms are mostly in the nose, they should receive topical nasal steroids before the beginning of the pollen season to minimize early damage to cells and inflammation, which would release aggravating substances such as histamines and tryptase. Eye treatment may also be necessary for mostly nasal sufferers.

If the eye is the source of most discomfort, choices are limited to the topical use of sodium cromoglycate in conjunction with nasal steroids to lessen general irritation. The only readily-available alternative to that is an oral antihistamine.

Should allergic rhinitis be really severe and treatment beyond the limits of such drugs, the patient will probably need to see a specialist who may, in a crisis, recommend short-term systemic corticosteroids. Immunotherapy may also be considered at this juncture. These more drastic treatments represent the weapons of last resort against seasonal allergic rhinitis at present, but with allergic mechanisms better understood every year, it may not be that way for long.