Alan Nathan discusses treatment for this common pollen allergy

WHAT’S AVAILABLE

• Antihistamines – oral
• Anti-inflammatories – nasal sprays, eye drops
• Allergen barrier – nasal spray.

ORAL ANTIHISTAMINES

How do they act?

Histamine is the principal chemical mediator responsible for the inflammatory response of hay fever. Antihistamines act as competitive histamine antagonists at the H1-receptor. There are two types:

• Sedating (first-generation) antihistamines are lipophilic and cross the blood–brain barrier readily. In the brain, in addition to binding to H1-receptors, they bind to and block muscarinic receptors and, in some cases, alpha-adrenoceptors and serotonergic receptors. As a result, they cause several generally undesirable side effects such as sedation, dry mouth, blurred vision, urinary retention, constipation and gastrointestinal disturbances.
• Non-sedating (second-generation) antihistamines are less lipophilic and do not penetrate the brain to a significant extent, and are less likely to cause centrally mediated side effects.

Antihistamines are generally effective in controlling the symptoms of hay fever, including sneezing, nasal itching, rhinorrhoea and, to a lesser extent, allergic conjunctivitis, but have little or no effect on nasal congestion.

The maximum effect of antihistamines is not achieved until several hours after peak serum levels have been reached

The maximum effect of antihistamines is not achieved until several hours after peak serum levels have been reached; in addition they cannot reverse the consequences of H1-receptor activation, and are effective only if they are able to block histamine release before it occurs. For maximum effectiveness, therefore, antihistamines should be taken when symptoms are expected, rather than after they have started.

Sedating antihistamines

Compounds marketed for OTC sale for hay fever are:

• Chlorphenamine
• Clemastine
• Cyproheptadine
• Diphenhydramine
• Promethazine
• Triprolidine.

There is no evidence of difference in effectiveness between older antihistamines, although individual response to specific drugs varies widely. Choice is often based on personal preference and factors such as degree of sedation caused and duration of action, which do differ between compounds.

• Promethazine is highly sedative but has a long half-life, and a single dose may provide symptom relief for up to 24 hours. The dose is preferably taken at night, on the assumption that the sedative effect will have largely worn off by the following morning.
• Clemastine has an intermediate sedative effect (about 20 per cent greater than placebo) and a duration of action of up to 12 hours.
• Chlorphenamine is about as sedating as clemastine, with a faster onset but shorter duration of action.
• Diphenhydramine has pronounced sedative properties.

Non-sedating antihistamines

In hay fever, these are generally preferable to the older antihistamines because of their lower incidence of side effects. Compounds available are:

• Acrivastine – a rapid onset of action and a short half-life, requiring more frequent dosing than cetirizine or loratadine, but it may be useful to provide rapid relief.
• Cetirizine – peak plasma levels of cetirizine and loratadine are reached in about 1 hour; they have a long elimination half-life and are long acting, requiring only once-daily dosage.
• Loratadine – is metabolised in the liver by cytochrome P450 isoenzymes CYP3A4 and CYP2D6, and theoretically can interact with drugs that inhibit or are metabolised by these enzymes.

Combination products

Some products containing combinations of antihistamines with a sympathomimetic decongestant are marketed for treating nasal congestion associated with hay fever. Antihistamines alone are effective for treating the typical symptoms of acute hay fever, known as the early phase. Prolongation of the condition by continued exposure to the allergen leads to a late-phase sustained response, producing mucus secretion in the nasal passages and increased permeability of the capillaries, resulting in submucosal swelling and blockage. First-generation antihistamines reduce rhinorrhoea through their antimuscarinic action but do little to relieve nasal congestion and co-administration of a sympathomimetic decongestant may be helpful.

NASAL SPRAYS

Nasal preparations contain anti-inflammatory corticosteroids. Compounds available are:

• Beclometasone
• Fluticasone
• Triamcinolone

Nasal sprays and drops containing xylometazoline, a sympathomimetic decongestant, are also licensed for hay fever (see ICP Dec 14, p14).

How do they act?

Corticosteroids down-regulate the inflammatory response of type I allergic reactions by reducing the number of basophils and mast cells and blocking release of mediator substances. They inhibit both early and late responses to allergen exposure, and are therefore effective in relieving nasal congestion. They take some days to achieve optimum effect, and treatment should ideally be started at least two weeks before symptoms are expected.

Absorption from the nasal mucosa is low, and systemic effects are highly unlikely at recommended doses. Any local reactions, such as stinging, burning and aftertaste, are mild and transient. Long-term use appears to be safe. Treatment may need to be maintained throughout the hay fever season, and repeated each year. The recommended adult dosage is two sprays twice a day.

EYE DROPS

Most eye symptoms relating to hay fever will be controlled by oral antihistamines, but if symptoms are persistent or particularly troublesome eye drops are usually effective. Compounds available are:

• Mast cell stabilisers: sodium cromoglicate and lodoxamide
• Antazoline/xylometazoline, an antihistamine/sympathomimetic decongestant combination

Mast cell stabilisers

Mast cell stabilisers are thought to act by blocking a calcium channel essential for the degranulation of mast cells, thereby stabilising them and preventing the release of histamine produced in response to antigen stimulation. Sodium cromoglicate and lodoxamide are licensed for the treatment of seasonal allergic conjunctivitis in adults and children.

Antazoline/xylometazoline

Xylometazoline has vasoconstrictor action and is included as a conjunctival decongestant. The drops can be used for the short-term treatment of hay fever symptoms. However, prolonged use may raise intraocular pressure and precipitate glaucoma. The preparation is not suitable for use in children.

ALLERGEN BARRIER

A thixotropic gel nasal spray is available that forms a barrier preventing contact between allergens and the nasal mucosa. It is also claimed to control eye symptoms. It is licensed as a medical device.

How effective are OTC hay fever treatments?

• All OTC non-sedating antihistamines are of equal efficacy.¹
• The incidence of sedation is low for all second generation antihistamines, but loratadine is associated with a lower incidence of sedation than acrivastine or cetirizine, and has been recommended as the antihistamine of choice for people in occupations in which any degree of sedation is undesirable.²
• Several trials have found antihistamine-decongestant combinations to be more effective than an antihistamine alone.^3–5
• Intranasal corticosteroids are regarded as the treatment of choice for moderate-to-severe hay fever and are superior to oral antihistamines.⁶
• All three intranasal corticosteroids have been found to be of equivalent efficacy and safe in use; there is some evidence that fluticasone may be superior and faster acting.^7,8,9
• In a small trial, an allergen barrier spray was effective in preventing allergic reactions induced by dust mite allergen challenge.¹⁰

 

REFERENCES

1. Slater JW, Zechnich AD, Haxby DG. Second-generation antihistamines: a comparative review. Drugs 1999; 57:31–47.
2. Mann RD, Pearce GL, Dunn N, Shakir S. Sedation with ‘non-sedating’ antihistamines: four prescription-event monitoring studies in general practice. BMJ 2000; 320:1184–86.
3. Pleskow W, Grubbe R, Weiss S, Lutsky B. Efficacy and safety of an extended-release formulation of desloratadine and pseudoephedrine vs the individual components in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2005; 94:348–54.
4. Sussman GL, Mason J, Compton D, et al. The efficacy and safety of fexofenadine HCl and pseudoephedrine, alone and in combination, in seasonal allergic rhinitis. J Allergy Clin Immunol 1999; 104:100–106.
5. Nuutinen J, Holopainen E, Malmberg H, et al. Terfenadine with or without phenylpropanolamine in the treatment of seasonal allergic rhinitis. Clin Exp Allergy 1989; 19:603–8.
6. National Prescribing Centre. Common questions about hay fever. MeReC Bulletin 2004; 14, Number 5.
7. Sheik A, Panesar SP, Dhami S, Salvilla S. Seasonal allergic rhinitis in adolescents and adults. BMJ Clinical Evidence. November 2009. (http://clinicalevidence.bmj.com/x/systematic-review/0509/overview.html)
8. LaForce CF, Dockhorn RJ, Findlay SR, et al. Fluticasone propionate: an effective alternative treatment for seasonal allergic rhinitis in adults and adolescents. J Fam Pract 1994; 38:145–52.
9. an As A, Bronsky EA, Dockhorn RJ, et al. Once daily fluticasone propionate is as effective for perennial allergic rhinitis as twice daily beclomethasone diproprionate. J Allergy Clin Immunol 1993; 91:1146–54.
10. Stoelzel K, Bothe G, Win Chong P, Lenarz M. Safety and efficacy of Nasya/Prevalin in reducing symptoms of allergic rhinitis Clin Respir J. 2014; 8:382–90.