It is available in generic and brand versions. Diphenhydramine (Benadryl, Diphenhist, Unisom, Zzzquil) is an antihistamine used to treat symptoms of seasonal allergies including sneezing, runny nose, and itching or watering eyes.It is also used as an over-the-counter sleep aid. Benadryl (diphenhydramine) is a well-known antihistamine used to treat allergy symptoms including sneezing, runny nose, and itchy and watery eyes, as well as colds, dry coughs, insomnia, and motion sickness.While typically mild, the side effects of Benadryl may be more intense for some people—making using the drug undesirable, especially during the day, or even unsafe. Benadryl (diphenhydramine) is an antihistamine used to treat symptoms of seasonal allergies including sneezing, runny nose, and itching or watering eyes.It works by blocking the action of histamine which causes allergic symptoms.It is available over-the-counter, and also sold as generic diphenhydramine. Long-Term Side Effects of Diphenhydramine Abuse. Benadryl Injection (diphenhydramine hydrochloride) is an antihistamine used to treat life-threatening allergic reactions (anaphylaxis) along with epinephrine and other treatments.Benadryl Injection is also used to relieve symptoms of household allergies, hay fever and the common cold when medication cannot be given by mouth. Side Effects of Benadryl. Minimizing Side Effects of Diphenhydramine. Benadryl (diphenhydramine hydrochloride) is a brand name antihistamine drug with anticholinergic (drying) and sedative side effects manufactured by McNeil Healthcare, a division of Johnson & Johnson. Taking Benadryl with Zyrtec may increase the risk of certain side effects such as sleepiness, dry mouth, fatigue, and headache. There are side effects associated with using Benadryl for dogs that all dog owners should be aware of. The undesirable effects of Benadryl can be minimized and managed so that patients can continue with their day-to-day activities in an efficient manner. Continued diphenhydramine use can cause long-term adverse side effects that result in permanent damage. Not only will prolonged use cause harm, but it can lead to other aspects such as dependence on the medication. Common long-term side effects of prolonged diphenhydramine use include: Dependence. In the case of interacting with alcohol, Benadryl and Zyrtec are quite similar, even though the second one is a second-generation non-sedative antihistamine. In a study of older adults, diphenhydramine reduced awakenings but didn't improve sleep latency, total sleep time, or sleep quality. These side effects may go away during treatment as your body adjusts to the medicine. 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