What ingredient causes drowsiness in allergy medicine

Alcohol may increase the drowsiness caused by diphenhydramine.[45][46]



Site Ki (nM) Species Ref
SERT ≥3,800 Human [48][49]
NET 960–2,400 Human [48][49]
DAT 1,100–2,200 Human [48][49]
5-HT2A 260 Human [49]
5-HT2C 780 Human [49]
α1B 1,300 Human [49]
α2A 2,900 Human [49]
α2B 1,600 Human [49]
α2C 2,100 Human [49]
D2 20,000 Rat [50]
H1 9.6–16 Human [51][49][49]
H2 >100,000 Canine [52]
H3 >10,000 Human [49][53][54]
H4 >10,000 Human [54]
M1 80–100 Human [55][49]
M2 120–490 Human [55][49]
M3 84–229 Human [55][49]
M4 53–112 Human [55][49]
M5 30–260 Human [55][49]
VGSC 48,000–86,000 Rat [56]
hERG 27,100 (IC50) Human [57]
Values are Ki (nM), unless otherwise noted.

The smaller the worth, the more strongly the drug binds to the site.

What ingredient causes drowsiness in allergy medicine

Diphenhydramine, while traditionally known as an antagonist, acts primarily as an inverse agonist of the histamineH1 receptor.[58] It is a member of the ethanolamine class of antihistaminergic agents.[29] By reversing the effects of histamine on the capillaries, it can reduce the intensity of allergic symptoms. It also crosses the blood–brain barrier and inversely agonizes the H1 receptors centrally.[58] Its effects on central H1 receptors cause drowsiness.

Like numerous other first-generation antihistamines, diphenhydramine is also a potent antimuscarinic (a competitive antagonist of muscarinic acetylcholine receptors) and, as such, at high doses can cause anticholinergic syndrome.[59] The utility of diphenhydramine as an antiparkinson agent is the result of its blocking properties on the muscarinic acetylcholine receptors in the brain.

What ingredient causes drowsiness in allergy medicine

Diphenhydramine also acts as an intracellular sodium channel blocker, which is responsible for its actions as a local anesthetic.[56] Diphenhydramine has also been shown to inhibit the reuptake of serotonin.[60] It has been shown to be a potentiator of analgesia induced by morphine, but not by endogenous opioids, in rats.[61] The drug has also been found to act as an inhibitor of histamine N-methyltransferase (HNMT).[62][63]


Oral bioavailability of diphenhydramine is in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after istration.[3] The primary route of metabolism is two successive demethylations of the tertiary amine.

The resulting primary amine is further oxidized to the carboxylic acid.[3] The elimination half-life of diphenhydramine has not been fully elucidated, but appears to range between 2.4 and 9.3 hours in healthy adults.[4] A 1985 review of antihistamine pharmacokinetics found that the elimination half-life of diphenhydramine ranged between 3.4 and 9.3 hours across five studies, with a median elimination half-life of 4.3 hours.[3] A subsequent 1990 study found that the elimination half-life of diphenhydramine was 5.4 hours in children, 9.2 hours in young adults, and 13.5 hours in the elderly.[5]

Medical uses

Diphenhydramine is a first-generation antihistamine used to treat a number of conditions including allergic symptoms and itchiness, the common freezing, insomnia, motion sickness, and extrapyramidal symptoms.[16][17] Diphenhydramine also has local anesthetic properties, and has been used as such in people allergic to common local anesthetics such as lidocaine.[18]


Diphenhydramine is effective in treatment of allergies.[19] As of 2007[update], it was the most commonly used antihistamine for acute allergic reactions in the emergency department.[20]

By injection it is often used in addition to epinephrine for anaphylaxis.[21] Its use for this purpose had not been properly studied as of 2007[update].[22] Its use is only recommended once acute symptoms own improved.[19]

Topical formulations of diphenhydramine are available, including creams, lotions, gels, and sprays.

What ingredient causes drowsiness in allergy medicine

These are used to relieve itching and own the advantage of causing fewer systemic effects (e.g., drowsiness) than oral forms.[23]


Because of its sedative properties, diphenhydramine is widely used in nonprescription sleep aids for insomnia. The drug is an ingredient in several products sold as sleep aids, either alone or in combination with other ingredients such as acetaminophen (paracetamol) in Tylenol PM or ibuprofen in Advil PM. Diphenhydramine can cause minor psychological dependence.[25] Diphenhydramine can cause sedation and has also been used as an anxiolytic.[26]


Diphenhydramine also has antiemetic properties, which make it useful in treating the nausea that occurs in vertigo and motion sickness.[27]

Movement disorders

Diphenhydramine is used to treat Parkinson’s disease–likeextrapyramidal symptoms caused by antipsychotics.[24]

Special populations

Diphenhydramine is not recommended for people older than 60 or children under the age of six, unless a physician is consulted.[7][8][28] These populations should be treated with second-generation antihistamines such as loratadine, desloratadine, fexofenadine, cetirizine, levocetirizine, and azelastine.[29] Due to its strong anticholinergic effects, diphenhydramine is on the Beers list of drugs to avoid in the elderly.[30][31]

Diphenhydramine is category B in the FDA Classification of Drug Safety During Pregnancy.[32] It is also excreted in breast milk.[33]Paradoxical reactions to diphenhydramine own been documented, in specific among children, and it may cause excitation instead of sedation.[34]

Topical diphenhydramine is sometimes used especially for people in hospice.

What ingredient causes drowsiness in allergy medicine

This use is without indication and topical diphenhydramine should not be used as treatment for nausea because research does not indicate this therapy is more effective than alternatives.[35]


Diphenhydramine overdose symptoms may include:[41]

Acute poisoning can be fatal, leading to cardiovascular collapse and death in 2–18 hours, and in general is treated using a symptomatic and supportive approach.[29] Diagnosis of toxicity is based on history and clinical presentation, and in general specific levels are not useful.[42] Several levels of evidence strongly indicate diphenhydramine (similar to chlorpheniramine) can block the delayed rectifierpotassium channel and, as a consequence, prolong the QT interval, leading to cardiac arrhythmias such as torsades de pointes.[43] No specific antidote for diphenhydramine toxicity is known, but the anticholinergic syndrome has been treated with physostigmine for severe delirium or tachycardia.[42]Benzodiazepines may be istered to decrease the likelihood of psychosis, agitation, and seizures in people who are prone to these symptoms.[44]

Adverse effects

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.[20]

Diphenhydramine is a potent anticholinergic agent.

What ingredient causes drowsiness in allergy medicine

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.[36]

Some people own an allergic reaction to diphenhydramine in the form of hives.[37][38] However, restlessness or akathisia can also be a side effect made worse by increased levels of diphenhydramine, especially with recreational dosages.[34] Normal doses of diphenhydramine, love other first generation antihistamines, can make symptoms of restless legs syndrome worse.[39] 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.[40]


Diphenhydramine is a diphenylmethanederivative.

Analogues of diphenhydramine include orphenadrine, an anticholinergic, nefopam, an analgesic, and tofenacin, an antidepressant.

Detection in body fluids

Diphenhydramine can be quantified in blood, plasma, or serum.[64]Gas chromatography with mass spectrometry (GC-MS) can be used with electron ionization on full scan mode as a screening test.

What ingredient causes drowsiness in allergy medicine

GC-MS or GC-NDP can be used for quantification.[64] Rapid urine drug screens using immunoassays based on the principle of competitive binding may show false-positive methadone results for people having ingested diphenhydramine.[65] Quantification can be used to monitor therapy, confirm a diagnosis of poisoning in people who are hospitalized, provide evidence in an impaired driving arrest, or help in a death investigation.[64]