What are the differences between antihistamines? Others you can buy over the counter OTC at your local pharmacy. Interactions with other drugs are more common with first-generation antihistamines compared with second-generation antihistamines. But they can't relieve every symptom. Common antihistamines available in the U. Antihistamines also can be used on an as needed basis for those who experience occasional symptoms or symptoms triggered by exposure to certain irritants such as animal hair, plants, medications, and food products. The newer antihistamines second generation are less likely to cause these side effects.