Diphenhydramine
Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremors in parkinsonism, and nausea.[10] It is taken by mouth, injected into a vein, injected into a muscle, or applied to the skin.[10] Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours.[10]
Not to be confused with dimenhydrinate.
Common side effects include sleepiness, poor coordination and an upset stomach.[10] Its use is not recommended in young children or the elderly.[10][11] There is no clear risk of harm when used during pregnancy; however, use during breastfeeding is not recommended.[12] It is a first-generation H1-antihistamine and it works by blocking certain effects of histamine, which produces its antihistamine and sedative effects.[10][2] Diphenhydramine is also a potent anticholinergic, which means it also works as a deliriant at much higher than recommended doses as a result.[13] Its sedative and deliriant effects have led to some cases of recreational use.[14][2]
Diphenhydramine was first developed by George Rieveschl and came into commercial use in 1946.[15][16] It is available as a generic medication.[10] It is sold under the brand name Benadryl, among others.[10] In 2021, it was the 242nd most commonly prescribed medication in the United States, with more than 1 million prescriptions.[17][18]
Adverse effects[edit]
The most prominent side effect is sedation. A typical dose creates driving impairment equivalent to a blood-alcohol level of 0.10, which is higher than the 0.08 limit of most drunk-driving laws.[23]
Diphenhydramine is a potent anticholinergic agent and potential deliriant in higher doses. This activity is responsible for the side effects of dry mouth and throat, increased heart rate, pupil dilation, urinary retention, constipation, and, at high doses, hallucinations or delirium. Other side effects include motor impairment (ataxia), flushed skin, blurred vision at nearpoint owing to lack of accommodation (cycloplegia), abnormal sensitivity to bright light (photophobia), sedation, difficulty concentrating, short-term memory loss, visual disturbances, irregular breathing, dizziness, irritability, itchy skin, confusion, increased body temperature (in general, in the hands and/or feet), temporary erectile dysfunction, and excitability, and although it can be used to treat nausea, higher doses may cause vomiting.[45] Diphenhydramine in overdose may occasionally result in QT prolongation.[46]
Some individuals experience an allergic reaction to diphenhydramine in the form of hives.[47][48]
Conditions such as restlessness or akathisia can worsen from increased levels of diphenhydramine, especially with recreational dosages.[42] Normal doses of diphenhydramine, like other first generation antihistamines, can also make symptoms of restless legs syndrome worse.[49]
As diphenhydramine is extensively metabolized by the liver, caution should be exercised when giving the drug to individuals with hepatic impairment.
Anticholinergic use later in life is associated with an increased risk for cognitive decline and dementia among older people.[50]
Contraindications[edit]
Diphenhydramine is contraindicated in premature infants and neonates, as well as people who are breastfeeding. It is a pregnancy Category B drug. Diphenhydramine has additive effects with alcohol and other CNS depressants. Monoamine oxidase inhibitors prolong and intensify the anticholinergic effect of antihistamines.[51]
History[edit]
Diphenhydramine was discovered in 1943 by George Rieveschl, a former professor at the University of Cincinnati.[88][89] In 1946, it became the first prescription antihistamine approved by the U.S. FDA.[90]
In the 1960s, diphenhydramine was found to weakly inhibit reuptake of the neurotransmitter serotonin.[80] This discovery led to a search for viable antidepressants with similar structures and fewer side effects, culminating in the invention of fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI).[80][91] A similar search had previously led to the synthesis of the first SSRI, zimelidine, from brompheniramine, also an antihistamine.[92]
In 1975, diphenhydramine was still available only by prescription in the U.S. and required medical supervision.[93]