Histamine is the main chemical mediator responsible for the inflammatory response of hay fever. All oral formulations for treatment of hay fever are antihistamines and act through competitive antagonism of histamine at the H1-receptor.

Systemic antihistamines are generally effective in controlling symptoms of hay fever, including sneezing, nasal itching, rhinorrhoea and, to a lesser extent, allergic conjunctivitis, but they have little or no effect on nasal congestion. The maximum effect is not achieved until several hours after peak serum levels have been reached and they cannot reverse the consequences of H1-receptor activation, so are only effective 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.

Oral antihistamines fall into two groups€“ sedating and non-sedating:

Sedating antihistamines

These are lipophilic and readily cross the blood€“brain barrier. As well as binding to H1-receptors, they bind to and block muscarinic receptors and, in some cases, alpha-adrenergic and serotonergic receptors in the brain. As a result they can cause several generally undesirable side-effects, including sedation, dry mouth, blurred vision, urinary retention, constipation and gastrointestinal disturbances.

Sedating antihistamines available without prescription are chlorphenamine, clemastine, cyproheptadine, diphenhydramine and promethazine. There is no evidence of difference in effectiveness between them, although individual response to specific drugs varies widely. Choice is often based on personal preference and factors such as the degree of sedation caused and duration of action, which do differ between compounds.

Non-sedating antihistamines

In comparison with sedating antihistamines, non-sedating antihistamines are less lipophilic. They do not reach the brain to a significant extent and are much less likely to cause centrally mediated adverse side-effects. However, some individuals exhibit drowsiness and other central nervous system side-effects in response to them, and impairment of function, if it occurs, is not always accompanied by subjective feelings of drowsiness. Patients should therefore be warned that these antihistamines may affect driving and other skilled tasks and that excess alcohol should be avoided.

Compounds available are acrivastine, cetirizine and loratadine. All are of equal efficacy. Acrivastine has a rapid onset of action and a short half-life, necessitating more frequent dosing than cetirizine or loratadine, but it may be 

useful to give rapid relief. Peak plasma levels of cetirizine and loratadine are reached in about an hour; they have long elimination half-lives and are long-acting, requiring only once-daily dosage. The incidence of sedation is extremely low for all three drugs, but loratadine is less likely to be sedating than acrivastine or cetirizine.

Combination products Some oral products combine antihistamines with sympathomimetic decongestants and are marketed for nasal congestion associated with hay fever and with the common cold. Antihistamines on their own are effective for treating the early-phase symptoms of hayfever. Sedating antihistamines reduce rhinorrhoea through their anticholinergic action but do little to relieve the nasal congestion associated with the late-phase response; co-administration of a sympathomimetic decongestant may be helpful.