From the Guidelines
Second-generation antihistamines are generally preferred over first-generation antihistamines due to their improved side effect profile and convenient dosing schedule. The primary differences between first-generation (Gen I) and second-generation (Gen II) antihistamines lie in their side effect profiles and dosing schedules. First-generation antihistamines, such as diphenhydramine, chlorpheniramine, and hydroxyzine, readily cross the blood-brain barrier, causing significant sedation, drowsiness, and cognitive impairment, as well as anticholinergic effects including dry mouth, blurred vision, urinary retention, and constipation 1. In contrast, second-generation antihistamines, including cetirizine, loratadine, fexofenadine, and desloratadine, are more selective for peripheral H1 receptors and have limited penetration of the blood-brain barrier, resulting in minimal sedation and generally lacking anticholinergic effects 1.
Some key points to consider when differentiating between Gen I and Gen II antihistamines include:
- Sedative properties: Fexofenadine, loratadine, and desloratadine do not cause sedation at recommended doses, while loratadine and desloratadine may cause sedation at doses exceeding the recommended dose; cetirizine and intranasal azelastine may cause sedation at recommended doses 1.
- Anticholinergic effects: First-generation antihistamines can cause dry mouth, constipation, and urinary retention, among other effects, which can be particularly problematic in older adults or those with certain comorbid conditions 1.
- Dosing schedule: Second-generation antihistamines often offer the convenience of once-daily dosing due to their longer half-lives, whereas first-generation antihistamines typically require dosing every 4-6 hours 1.
Given these differences, second-generation antihistamines are the preferred first-line treatment for allergic conditions like allergic rhinitis, urticaria, and other histamine-mediated reactions, although first-generation options may still be useful in specific situations where sedation is desired, such as for sleep or acute allergic reactions with significant itching 1.
From the Research
Differences between Gen I and Gen II Antihistamines
- The primary difference between first-generation (Gen I) and second-generation (Gen II) antihistamines is their ability to cross the blood-brain barrier, which affects their sedative properties 2, 3.
- Gen I antihistamines, such as diphenhydramine, can cause significant sedation, impairing performance, and decreasing alertness, whereas Gen II antihistamines, like loratadine, cetirizine, and fexofenadine, are less likely to produce sedation 2, 4.
- Gen II antihistamines have been shown to have excellent safety records, with minimal cardiovascular risks and no significant interactions with other medications 2, 5.
- Within the Gen II category, there are differences in the side effect profiles of individual medications, such as cetirizine, which can cause some sedation, whereas fexofenadine is nonsedating even at high doses 2, 5, 4.
- The choice of antihistamine depends on the specific needs of the patient, including the severity of symptoms, potential for sedation, and individual response to treatment 3, 6.
Efficacy and Safety
- Gen II antihistamines are effective in treating allergic disorders, such as seasonal allergic rhinitis and chronic urticaria, with minimal adverse effects 3, 5.
- Fexofenadine may offer the best overall balance of effectiveness and safety among Gen II antihistamines, while cetirizine is the most potent and suitable for patients with severe symptoms 5.
- Newer antihistamines, including Gen II options, provide similar efficacy to Gen I antihistamines but with less sedation, making them a preferable choice for managing acute allergic reactions 4.