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Can You Take Diphenhydramine Hcl and Melatonin Together

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Antihistamine medication

Diphenhydramine
Diphenhydramine 2D skeletal.svg
Diphenhydramine 3D 2aot.png
Clinical data
Pronunciation
Trade names Benadryl, Unisom, Nytol, others
AHFS/Drugs.com Monograph
MedlinePlus a682539
Pregnancy
category
  • AU: A
Dependence
liability		 Very low[one]
Routes of
administration		 By mouth, intramuscular injection, intravenous, topical, rectal
ATC code
  • D04AA32 (WHO) D04AA33 (WHO), R06AA02 (WHO)
Legal status
Legal status
  • AU: S2 (Pharmacy medicine)
  • Great britain: General sales list (GSL, OTC)
  • Us: OTC
Pharmacokinetic data
Bioavailability 40–threescore%[2]
Poly peptide binding 98–99%
Metabolism Liver (CYP2D6, others)[6] [7]
Elimination half-life Range: 2.four–xiii.v h[3] [2] [4]
Excretion Urine: 94%[5]
Carrion: 6%[5]
Identifiers

IUPAC name

  • 2-(diphenylmethoxy)-North,N-dimethylethanamine
CAS Number
  • 58-73-1 check Y
PubChem CID
  • 3100
IUPHAR/BPS
  • 1224
DrugBank
  • DB01075 check Y
ChemSpider
  • 2989 check Y
UNII
  • 8GTS82S83M
KEGG
  • D00669 ☒ N
ChEBI
  • CHEBI:4636 check Y
ChEMBL
  • ChEMBL657 check Y
CompTox Dashboard (EPA)
  • DTXSID4022949 Edit this at Wikidata
ECHA InfoCard 100.000.360 Edit this at Wikidata
Chemic and physical data
Formula C 17 H 21 N O
Molar mass 255.355 g·mol−one
3D model (JSmol)
  • Interactive image

SMILES

  • O(CCN(C)C)C(c1ccccc1)c2ccccc2

InChI

  • InChI=1S/C17H21NO/c1-18(2)13-14-19-17(15-9-v-3-6-ten-15)16-11-seven-4-8-12-sixteen/h3-12,17H,xiii-14H2,ane-2H3check Y

  • Primal:ZZVUWRFHKOJYTH-UHFFFAOYSA-Northcheck Y

☒ North check Y  (what is this?) (verify)

Diphenhydramine is an antihistamine mainly used to treat allergies.[8] It can as well be used for indisposition, symptoms of the mutual cold, tremor in parkinsonism, and nausea.[eight] Information technology is used by mouth, injection into a vein, injection into a muscle, or applied to the skin.[8] Maximal event is typically effectually two hours afterwards a dose, and effects can final for up to seven hours.[8]

Common side effects include sleepiness, poor coordination and an upset stomach.[8] Its use is not recommended in immature children or the elderly.[viii] [9] At that place is no clear risk of harm when used during pregnancy; all the same, use during breastfeeding is not recommended.[x] It is a first generation Hane-antihistamine and ethanolamine and works by blocking certain effects of histamine.[viii] Diphenhydramine is also an anticholinergic.[eleven]

Diphenhydramine was kickoff made by George Rieveschl and came into commercial use in 1946.[12] [thirteen] It is available as a generic medication.[8] It is sold nether the trade proper name Benadryl, among others.[8] In 2017, it was the 241st nearly usually prescribed medication in the United States, with more than ii million prescriptions.[14] [fifteen]

Medical uses [edit]

Diphenhydramine is a beginning-generation antihistamine used to treat a number of conditions including allergic symptoms and itchiness, the mutual cold, insomnia, movement sickness, and extrapyramidal symptoms.[sixteen] [17] Diphenhydramine also has local anesthetic properties, and has been used as such in people allergic to common local anesthetics such as lidocaine.[eighteen]

Allergies [edit]

Diphenhydramine is constructive in treatment of allergies.[nineteen] As of 2007[update], it was the most commonly used antihistamine for astute allergic reactions in the emergency section.[20]

By injection it is often used in addition to epinephrine for anaphylaxis,[21] although as of 2007[update] its use for this purpose had non been properly studied.[22] Its use is only recommended once acute symptoms have improved.[19]

A bottle of topical "Itch-Stopping Gel" diphenhydramine

Topical formulations of diphenhydramine are available, including creams, lotions, gels, and sprays. These are used to relieve itching and have the reward of causing fewer systemic effects (e.thousand., drowsiness) than oral forms.[23]

Movement disorders [edit]

Diphenhydramine is used to treat akathisia and Parkinson's disease–like extrapyramidal symptoms caused past antipsychotics.[24] Information technology is besides used to treat astute dystonia including torticollis and oculogyric crisis caused by first generation antipsychotics.

Slumber [edit]

Considering of its sedative properties, diphenhydramine is widely used in nonprescription sleep aids for insomnia. The drug is an ingredient in several products sold as slumber 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 has as well been used every bit an anxiolytic.[26]

Diphenhydramine has too been used off prescription by parents in an attempt to make their children sleep or remain sedated on long-distance flights.[27] This has been met with criticism, both by doctors and members of the airline industry, as sedating immature passengers may put them at risk if the flight encounters an emergency and they are unable to react to the situation efficiently,[28] and the drug'southward side furnishings, especially the chance of a paradoxical reaction, may result in some individuals becoming hyperactive rather than sedated. The ethics of this use have as well been challenged, with the Seattle Children's hospital arguing in a 2009 commodity that 'Using a medication for your convenience is never an indication for medication in a child.'[29]

Doses of diphenhydramine that take been used for sleep range from 12.five to 100 mg, with a typical dose of 50 mg.[xxx] [31] [32] [33] [34]

Nausea [edit]

Diphenhydramine also has antiemetic properties, which go far useful in treating the nausea that occurs in vertigo and motion sickness.[35]

Special populations [edit]

Diphenhydramine is not recommended for people older than 60 or children nether the age of six, unless a physician is consulted.[8] [9] [36] These populations should be treated with second-generation antihistamines such as loratadine, desloratadine, fexofenadine, cetirizine, levocetirizine, and azelastine.[37] Due to its stiff anticholinergic effects, diphenhydramine is on the Beers list of drugs to avoid in the elderly.[38] [39]

Diphenhydramine is category B in the FDA Classification of Drug Rubber During Pregnancy.[twoscore] It is also excreted in breast milk.[41] It is expected that low doses of diphenhydramine taken occasionally will non cause whatever adverse effects on breastfed infants. Big doses or long-term use may affect the baby or reduce breast milk supply, especially when combined with sympathomimetic drugs such as pseudoephedrine or earlier the institution of lactation. A single bedtime dose after the concluding feeding of the day may minimize whatsoever harmful effects of the medication on the baby and on the milk supply. Nonetheless, non-sedating antihistamines are the preferred alternative.[42]

Paradoxical reactions to diphenhydramine take been documented, in particular amongst children, and it may cause excitation instead of sedation.[43]

Topical diphenhydramine is sometimes used especially for people in hospice. This apply is without indication and topical diphenhydramine should non be used as treatment for nausea considering research does non indicate this therapy is more effective than alternatives.[44]

In that location were no documented cases of clinically credible acute liver injury caused by normal doses of diphenhydramine.[45]

Adverse effects [edit]

The nearly prominent side upshot is sedation. A typical dose creates driving impairment equivalent to a claret-alcohol level of 0.10, which is college than the 0.08 limit of most drunk-driving laws.[20]

Diphenhydramine is a stiff anticholinergic amanuensis and potential deliriant in college 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 adaptation (cycloplegia), aberrant sensitivity to vivid light (photophobia), sedation, difficulty concentrating, curt-term memory loss, visual disturbances, irregular animate, dizziness, irritability, itchy skin, confusion, increased body temperature (in general, in the hands and/or anxiety), temporary erectile dysfunction, and excitability, and although information technology can exist used to treat nausea, higher doses may cause vomiting.[46] Diphenhydramine in overdose may occasionally consequence in QT prolongation.[47]

Some individuals experience an allergic reaction to diphenhydramine in the form of hives.[48] [49]

Conditions such as restlessness or akathisia can worsen from increased levels of diphenhydramine, specially with recreational dosages.[43] Normal doses of diphenhydramine, like other beginning generation antihistamines, tin also make symptoms of restless legs syndrome worse.[fifty] Equally diphenhydramine is extensively metabolized by the liver, caution should exist exercised when giving the drug to individuals with hepatic harm.

Anticholinergic use later in life is associated with an increased risk for cognitive decline and dementia among older people.[51]

Contraindications [edit]

Diphenhydramine is contraindicated in premature infants and neonates too as breastfeeding mothers. Information technology is a pregnancy Category B drug. Diphenhydramine has additive effects with booze and other CNS depressants. Monoamine Oxidase inhibitors prolong and intensify the anticholinergic consequence of antihistamines. [52]

Overdose [edit]

Diphenhydramine is 1 of the most usually misused over the counter drugs in the United States.[53] In cases of extreme overdose, if not treated in fourth dimension, acute diphenhydramine poisoning may take serious and potentially fatal consequences. Overdose symptoms may include:[54]

  • Euphoria or dysphoria
  • Hallucinations (auditory, visual, etc.)
  • Heart palpitations
  • Farthermost drowsiness
  • Severe dizziness
  • Abnormal speech communication (inaudibility, forced oral communication, etc.)
  • Flushed pare
  • Severe mouth and throat dryness
  • Tremors
  • Seizures
  • Inability to urinate
  • Vomiting
  • Acute megacolon
  • Motor disturbances
  • Anxiety/nervousness
  • Disorientation
  • Abdominal pain
  • Delirium
  • Coma
  • Death

Acute poisoning can be fatal, leading to cardiovascular collapse and death in ii–18 hours, and in general is treated using a symptomatic and supportive approach.[37] Diagnosis of toxicity is based on history and clinical presentation, and in general specific levels are not useful.[55] Several levels of show strongly indicate diphenhydramine (similar to chlorpheniramine) can block the delayed rectifier potassium channel and, equally a issue, prolong the QT interval, leading to cardiac arrhythmias such equally torsades de pointes.[56] No specific antitoxin for diphenhydramine toxicity is known, but the anticholinergic syndrome has been treated with physostigmine for severe delirium or tachycardia.[55] Benzodiazepines may be administered to decrease the likelihood of psychosis, agitation, and seizures in people who are prone to these symptoms.[57]

Interactions [edit]

Booze may increment the drowsiness caused by diphenhydramine.[58] [59]

Pharmacology [edit]

Pharmacodynamics [edit]


Diphenhydramine[60]
Site Ki (nM) Species Ref
SERT ≥3,800 Human [61] [62]
Net 960–2,400 Human [61] [62]
DAT 1,100–two,200 Human [61] [62]
v-HT2A 260 Homo [62]
v-HT2C 780 Human being [62]
α1B 1,300 Human [62]
α2A two,900 Human [62]
α2B 1,600 Human [62]
α2C 2,100 Human being [62]
Dii 20,000 Rat [63]
Hi 9.half dozen–16 Human [64] [62]
H2 >100,000 Canine [65]
H3 >10,000 Man [62] [66] [67]
Hfour >10,000 Man [67]
M1 80–100 Human [68] [62]
Mtwo 120–490 Human [68] [62]
Mthree 84–229 Human [68] [62]
10004 53–112 Human [68] [62]
Chiliad5 xxx–260 Human [68] [62]
VGSC 48,000–86,000 Rat [69]
hERG 27,100 (IC50 ) Man [seventy]
Values are Mi (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.

Diphenhydramine, while traditionally known as an antagonist, acts primarily as an changed agonist of the histamine Hane receptor.[71] It is a fellow member of the ethanolamine class of antihistaminergic agents.[37] By reversing the effects of histamine on the capillaries, it can reduce the intensity of allergic symptoms. Information technology also crosses the blood–brain barrier and inversely agonizes the Hone receptors centrally.[71] Its furnishings on cardinal H1 receptors cause drowsiness.

Like many other first-generation antihistamines, diphenhydramine is also a potent antimuscarinic (a competitive antagonist of muscarinic acetylcholine receptors) and, every bit such, at loftier doses can crusade anticholinergic syndrome.[72] The utility of diphenhydramine as an antiparkinson agent is the outcome of its blocking backdrop on the muscarinic acetylcholine receptors in the encephalon.

Diphenhydramine besides acts as an intracellular sodium channel blocker, which is responsible for its deportment as a local coldhearted.[69] Diphenhydramine has also been shown to inhibit the reuptake of serotonin.[73] It has been shown to exist a potentiator of analgesia induced by morphine, but not by endogenous opioids, in rats.[74] The drug has also been found to act as an inhibitor of histamine N-methyltransferase (HNMT).[75] [76]

Overview of diphenhydramine targets and effects
Biological target Fashion of action Effect
H1 receptor Inverse agonist Allergy reduction; Sedation
mACh receptors Antagonist Anticholinergic; Antiparkinson
Sodium channels Blocker Local coldhearted

Pharmacokinetics [edit]

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

The primary route of metabolism is two successive demethylations of the 3rd amine. The resulting primary amine is further oxidized to the carboxylic acrid.[2] Diphenhydramine is metabolized by the cytochrome P450 enzymes CYP2D6, CYP1A2, CYP2C9, and CYP2C19.[half-dozen]

The elimination half-life of diphenhydramine has non been fully elucidated, simply appears to range between 2.4 and 9.three hours in salubrious adults.[three] A 1985 review of antihistamine pharmacokinetics found that the emptying one-half-life of diphenhydramine ranged between iii.4 and ix.iii hours across five studies, with a median elimination one-half-life of 4.3 hours.[2] A subsequent 1990 study establish that the elimination half-life of diphenhydramine was v.iv hours in children, ix.2 hours in immature adults, and 13.v hours in the elderly.[4] A 1998 study establish a half-life of 4.one ± 0.iii hours in young men, 7.iv ± 3.0 hours in elderly men, 4.4 ± 0.3 hours in young women, and 4.9 ± 0.six hours in elderly women.[77] In a 2022 study in children and adolescents, the half-life of diphenhydramine was 8 to 9 hours.[78]

Chemistry [edit]

Diphenhydramine is a diphenylmethane derivative. Analogues of diphenhydramine include orphenadrine, an anticholinergic, nefopam, an analgesic, and tofenacin, an antidepressant.

Detection in body fluids [edit]

Diphenhydramine can be quantified in blood, plasma, or serum.[79] Gas chromatography with mass spectrometry (GC-MS) can be used with electron ionization on total scan style as a screening test. GC-MS or GC-NDP can be used for quantification.[79] Rapid urine drug screens using immunoassays based on the principle of competitive binding may show false-positive methadone results for people having ingested diphenhydramine.[fourscore] Quantification can exist used to monitor therapy, ostend a diagnosis of poisoning in people who are hospitalized, provide testify in an impaired driving arrest, or help in a death investigation.[79]

History [edit]

Diphenhydramine was discovered in 1943 by George Rieveschl, a erstwhile professor at the University of Cincinnati.[81] [82] In 1946, it became the starting time prescription antihistamine canonical past the U.South. FDA.[83]

In the 1960s, diphenhydramine was constitute to weakly inhibit reuptake of the neurotransmitter serotonin.[73] This discovery led to a search for viable antidepressants with similar structures and fewer side furnishings, culminating in the invention of fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI).[73] [84] A similar search had previously led to the synthesis of the offset SSRI, zimelidine, from brompheniramine, also an antihistamine.[85]

Social club and culture [edit]

Diphenhydramine is deemed to have express abuse potential in the U.s.a. attributable to its potentially serious side-effect profile and express euphoric furnishings, and is not a controlled substance. Since 2002, the U.S. FDA has required special labeling alarm against use of multiple products that contain diphenhydramine.[86] In some jurisdictions, diphenhydramine is often present in postmortem specimens nerveless during investigation of sudden baby deaths; the drug may play a role in these events.[87] [88]

Diphenhydramine is among prohibited and controlled substances in the Zambia,[89] and travelers are advised not to bring the drug into the country. Several Americans have been detained by the Zambian Drug Enforcement Commission for possession of Benadryl and other over-the-counter medications containing diphenhydramine.[90]

Recreational use [edit]

Although diphenhydramine is widely used and by and large considered to be prophylactic for occasional usage, multiple cases of abuse and habit have been documented.[91] Considering the drug is cheap and sold over the counter in almost countries, adolescents without access to more than sought-after, illicit drugs are particularly at risk.[92] People with mental health problems—specially those with schizophrenia—are likewise decumbent to corruption the drug, which is cocky-administered in large doses to treat extrapyramidal symptoms caused by the apply of antipsychotics.[93]

Recreational users report calming effects, mild euphoria, and hallucinations every bit the desired furnishings of the drug.[93] [94] Enquiry has shown that antimuscarinic agents, including diphenhydramine, "may have antidepressant and mood-elevating properties".[95] A study conducted on adult males with a history of sedative abuse found that subjects who were administered a high dose (400 mg) of diphenhydramine reported a want to accept the drug again, despite besides reporting negative effects, such as difficulty concentrating, confusion, tremors, and blurred vision.[96]

In 2020, an Internet challenge emerged on social media platform TikTok involving deliberately overdosing on diphenhydramine; dubbed the Benadryl claiming, the challenge requires participants to overdose on Benadryl for the purpose of filming the resultant psychoactive furnishings, and has been implicated in several hospitalisations[97] and at least one death.[98] [99]

Names [edit]

Diphenhydramine is marketed nether the merchandise name Benadryl past McNeil Consumer Healthcare in the U.South., Canada, and South Africa.[100] Trade names in other countries include Dimedrol, Daedalon, and Nytol. Information technology is also available as a generic medication.

Procter & Gamble markets an over-the-counter conception of diphenhydramine as a sleep aid under the make ZzzQuil. In 2022 this product had almanac sales of over $120 million and had a 29.iii% share of the $411 one thousand thousand slumber-help market category.[101]

Run across also [edit]

  • Tripelennamine

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Further reading [edit]

  • Lieberman JA (2003). "History of the use of antidepressants in primary care" (PDF). Chief Care Companion J. Clinical Psychiatry. 5 (supplement 7): 6–10.
  • Cox D, Ahmed Z, McBride AJ (March 2001). "Diphenhydramine dependence". Addiction. 96 (3): 516–vii. PMID 11310441.
  • Björnsdóttir I, Einarson TR, Gudmundsson LS, Einarsdóttir RA (December 2007). "Efficacy of diphenhydramine confronting cough in humans: a review". Pharmacy World & Science. 29 (6): 577–83. doi:10.1007/s11096-007-9122-ii. PMID 17486423. S2CID 8168920.

External links [edit]

  • Drugs.com: Diphenhydramine
  • "Diphenhydramine". Drug Information Portal. U.S. National Library of Medicine.

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Source: https://en.wikipedia.org/wiki/Diphenhydramine

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