Diphenhydramine (DPH) is an antihistamine medication mainly used to treat allergies.

It is a  first-generation antihistamine.

It is also a potent antimuscarinic and, as such, at high doses can cause anticholinergic syndrome.

It can also be used for insomnia, symptoms of the common cold, tremor in parkinsonism, nausea, insomnia, motion sickness, and extrapyramidal symptoms.

It is taken by mouth, intravenously, intramuscular, rectally, or applied to the skin.

Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours.

Pregnancy category AU: A

Use during breastfeeding is not recommended.

In general: Over-the-counter (OTC)

Bioavailability 40–60%

Protein binding 98–99%

Metabolism Liver CYP2D6

Elimination half-life Range: 2.4–13.5 h

Excretion Urine: 94%

Feces: 6%

Common side effects: sleepiness, poor coordination and GI upset.

Its use is not recommended in young children or the elderly.

A first generation H1-antihistamine and and works by blocking certain effects of histamine.

IT is also a potent anticholinergic, and works as a deliriant at higher than recommended doses as a result.

There are some cases of recreational use and addiction.

Sold under the brand name Benadryl, among others.

It also has local anesthetic properties.

By injection it is often used in addition to epinephrine for anaphylaxis,once acute symptoms have improved.

Topical formulations are used to relieve itching and have the advantage of causing fewer systemic effects.

Diphenhydramine is used to treat akathisia and Parkinson’s disease–like extrapyramidal symptoms caused by antipsychotics.

It is used to treat acute dystonia including torticollis and oculogyric crisis caused by first generation antipsychotics.

Widely used in nonprescription sleep aids for insomnia. 

D is an ingredient in several products sold as sleep aids, either alone or in combination with other ingredients such as acetaminophen or ibuprofen.

Diphenhydramine can cause minor psychological dependence.

It  has also been used as an anxiolytic.

Diphenhydramine has also been used off prescription by parents in an attempt to make their children sleep or remain sedated on long-distance flights: highly criticized activity.

The use of diphenhydramine in the treatment of insomnia is discouraged due to poor effectiveness and low quality of evidence.

It’s antiemetic properties, make it useful in treating the nausea that occurs in vertigo and motion sickness.

It’s use is not recommended for people older than 60 or children under the age of six: it has strong anticholinergic effects and should be to avoided in the elderly.

It is is category B for Pregnancy.

It is also excreted in breast milk, and large doses or long-term use may affect the baby or reduce breast milk supply, especially when combined with sympathomimetic drugs such as pseudoephedrine or before the establishment of lactation. 

Paradoxical reactions occur, particularly among children, causing excitation instead of sedation.

Side effects: 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.

Other side effects include: motor impairment, ataxia, flushed skin, blurred vision owing to lack of accommodation, photophobia, sedation, difficulty concentrating, short-term memory loss, visual disturbances, irregular breathing, dizziness, irritability, itchy skin, confusion, increased body temperature 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.

It is is a potent anticholinergic agent responsible for dry mouth and throat, increased heart rate, pupil dilation, urinary retention, constipation, and, at high doses, hallucinations or delirium.

In overdose may occasionally result in QT prolongation.

Increased levels of diphenhydramine, especially with recreational dosages can cause restlessness or akathisia.

It can worsen restless legs syndrome worse.

It is extensively metabolized by the liver, and should be used with caution in individuals with hepatic impairment.

Anticholinergic is associated with an increased risk for cognitive decline and dementia among older people.

Diphenhydramine is contraindicated in premature infants and neonates as well as people who are breastfeeding. 

Diphenhydramine has additive effects with alcohol and other CNS depressants. 

Monoamine Oxidase inhibitors prolong and intensify the anticholinergic effect of antihistamines. 

Diphenhydramine is one of the most commonly misused over-the-counter drugs in the United States.

Acute diphenhydramine poisoning may have serious and potentially fatal consequences. 

Diphenhydramine overdose symptoms may include:

Euphoria or dysphoria

Hallucinations, both auditory, and visual.

Heart palpitations

Extreme drowsiness

Severe dizziness

Abnormal speech 


Mouth and throat dryness



Inability to urinate


Acute megacolon

Motor disturbances



Abdominal pain




Acute diphenhydramine poisoning can be fatal, leading to cardiovascular collapse and death in 2–18 hours.

Acute diphenhydramine poisoning is treated using a symptomatic and supportive approach.

Evidence exists to indicate diphenhydramine can block the delayed rectifier potassium channel and, as a consequence, prolong the QT interval, leading to cardiac arrhythmias such as torsades de pointes.

No specific antidote for diphenhydramine toxicity is known.

The anticholinergic syndrome has been treated with physostigmine May benefit delirium or tachycardia.

Benzodiazepines decrease the likelihood of psychosis, agitation, and seizures.

Alcohol may increase the drowsiness caused by diphenhydramine.

Diphenhydramine acts primarily as an inverse agonist of the histamine H1 receptor.

It reversing the effects of histamine on the capillaries, reducing the intensity of allergic symptoms. 

Diphenhydramine can cross  the blood–brain barrier and inversely agonizes the H1 receptors centrally causing drowsiness.

Diphenhydramine use as an antiparkinson agent is the result of its blocking properties on the muscarinic acetylcholine receptors in the brain.

Diphenhydramine also acts as an intracellular sodium channel blocker, and acts  as a local anesthetic.

Oral bioavailability is in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration.

Diphenhydramine is metabolized by the cytochrome P450 enzymes CYP2D6, CYP1A2, CYP2C9, and CYP2C19.

The elimination half-life ranges between 2.4 and 9.3 hours in healthy adults.

Diphenhydramine can be quantified in blood, plasma, or serum.

Urine drug screens using immunoassays based on the principle of competitive binding may show false-positive methadone results for people having ingested diphenhydramine.

Diphenhydraminemcan br measured to monitor therapy, confirm a diagnosis of poisoning,  provide evidence in an impaired driving arrest, or assist in a death investigation.

Diphenhydramine is often present in postmortem specimens collected during sudden infant deaths.

Multiple cases of abuse and addiction have been documented.

Recreational users report calming effects, mild euphoria, and hallucinations.

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