Variations among non-sedating antihistamines: are there real differences?

Most of the modern non-sedating H-1 receptor antagonists (antihistamines) p enetrate the brain poorly, allowing the use of doses large enough to counte ract allergic processes in peripheral tissues without important central eff ects. The antihistamines reviewed here are acrivastine, astemizole, cetirizine, e bastine, fexofenadine, loratadine, mizolastine, and terfenadine. However. t hese drugs are not entirely free from central effects, and there are at lea st quantitative differences between them. Although psychomotor and sleep studies in healthy subjects in the laborator y may predict that an antihistamine does not cause drowsiness, the safety m argin can be narrow enough to cause a central sedating effect during actual treatment. This might result from a patient's individual sensitivity, dise ase-induced sedation, or drug dosages that are for various reasons relative ly or absolutely larger (patient's weight, poor response, reduced drug clea rance, interactions). Mild to even moderate sedation is not necessarily a major nuisance, particu larly if stimulants need be added to the regimen (e.g. in perennial rhiniti s). Furthermore, patients can adjust doses themselves if needed. Sedating a ntihistamines are not needed for long-term itching, because glucocorticoids are indicated and more effective. It is wise to restrict or avoid using an tihistamines (astemizole, terfenadine) that can cause cardiac dysrhythmias, because even severe cardiotoxicity can occur in certain pharmacokinetic dr ug-drug interactions. Histamine H-1 receptor antagonists (antihistamines) are used in the treatme nt of allergic disorders. The therapeutic effects of most of the older anti histamines were associated with sedating effects on the central nervous sys tem (CNS) and antimuscarinic effects causing dry mouth and blurred vision. Non-specific "quinidine-like" or local anaesthetic actions often led to car diotoxicity in animals and man. Although such adverse effects varied from d rug to drug, there was some degree of sedation with all old antihistamines. Non-sedating antihistamines have become available during the past 15 years . Some of them also have antiserotonin or other actions that oppose allergi c inflammation, and they are not entirely free from sedative effects either . In small to moderate "clinical" concentrations they are competitive H-1 r eceptor antagonists, although large concentrations of some of them exert no n-competitive blockade. Daytime drowsiness and weakness are seldom really i mportant, and they restrict patients' activities less than the old antihist amines. Some new antihistamines share with old antihistamines quinidine-lik e effects on the cardiac conducting tissues, and clinically significant int eractions have raised the question of drug safety [1]. This prodysrhythmic effect has also been briefly mentioned in comparisons of non-sedative H-1 a ntihistamines.