Diphenhydramine, which is available as an over-the-counter medication, is a first-generation antihistamine that is used in a variety of conditions to treat and prevent dystonias, insomnia, pruritis, urticaria, vertigo, and motion sickness. It also possesses local anesthetic properties for those patients who have allergies to other, more commonly used local anesthetics; however, this is an off-label use of the medication. An additional off-label use is for the treatment of oral mucositis.
Diphenhydramine mainly works through antagonizing the H1 (Histamine 1) receptor, although it has other mechanisms of action as well.
The H1 receptor is located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons. When the H1 receptor is stimulated in these tissues it produces a wide variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and GIT, and eosinophilic chemotaxis promoting the allergic immune response.
Diphenhydramine acts as an inverse agonist at the H1 receptor, thereby reversing effects of histamine on capillaries, reducing allergic reaction symptoms.
Given that diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center.
The H1 receptor is similar to muscarinic receptors. Therefore, diphenhydramine also acts as an antimuscarinic; it is a competitive antagonist of muscarinic acetylcholine receptor, resulting in its use as an antiparkinson medication
Lastly, diphenhydramine acts as an intracellular sodium channel blocker, resulting in local anesthetic properties.
The liver metabolizes diphenhydramine via CYP450. It is excreted in the urine, unchanged, and has a half-life of 3.4-9.2h. Its time to peak, serum is 2 hours.
Diphenhydramine can be given by tablet, capsule, or in solution by mouth; by intramuscular (IM) or intravenous (IV) injection; or topically.
The following are recommended dosages for allergy symptoms:
More Severe Symptoms
Insomnia (Short Treatment)
Motion Sickness Prevention
Pruritis/Urticaria (Topical Treatment)
Common Adverse Effects
Obtain baseline creatinine level in pediatric patients.
Monitor all patients for mental alertness and relief of symptoms.
The intravenous infusion rate should be no higher than 25 mg/min.
Store at room temperature of 15 to 30 degrees C, and protect from freezing and light.
Diphenhydramine overdose can cause significant toxicity, ranging from agitation to cardiac arrhythmias to rhabdomyolysis and classic anticholinergic toxidrome. Signs and symptoms may include the following:
Treatment involves the following: