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Diphenhydramine
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[[File:Generic-Benadryl-Diphenhydramine-antishistamine.jpg|alt=Two bright pink diphenhydramine tablets (generic form of Benadryl)|thumb]] '''Diphenhydramine''' or '''diphenhydramine hydrochloride''' is a commonly used antihistamine, which is also used for coughs, to aid [[sleep dysfunction|sleep]], for certain symptoms of [[Parkinson's disease]], as well as for [[allergy]] symptoms, bites, [[skin itch|itching]] and [[eczema]].<ref name="drugscom">{{Cite web | url = https://www.drugs.com/diphenhydramine.html | title = Diphenhydramine Uses, Dosage & Side Effects|website=Drugs.com|language=en|access-date=2020-11-09}}</ref><ref name="NHS">{{Cite web | url = https://www.nhs.uk/medicines/diphenhydramine/ | title = Diphenhydramine (including Nytol Original & Histergan): drowsy antihistamine | last = | first = | authorlink = | date = 2018-09-21 | website = [[National Health Service]]|language=en| archive-url = | archive-date = |url-status = | access-date=2021-02-14}}</ref> Diphenhydramine is the active ingredient in '''Benadryl''', which is sometimes used as a sleep aid as well as an anti-histamine.<ref name="drugscom" /> === Additional active ingredients === Many products containing diphenhydramine contain other ingredients, for example: * [[acetaminophen]] (paracetamol) for night-time pain relief * expectorants like [[guaifenesin]], or [[Dextromethorphan|dextromethorphan hydrobromide]] in cough products<ref name="medicines">{{Cite web | url = https://www.medicines.org.uk/emc/search?q=Diphenhydramine&filters=activeingredients%5B191%5D&offset=1&limit=50&orderBy=product&refreshFilters=true | title = Search results - Diphenhydramine | last = | first = | date = |website=Electronic Medicines Compendium| archive-url = | archive-date = |url-status = | access-date=2021-02-13}}</ref> * [[levopenthol]], a decongestant and [[Analgesics|pain reliever]]<ref name="medicines" /><ref name="levomenthol">{{Cite web | url = https://www.drugs.com/international/levomenthol.html | title = Levomenthol|website=Drugs.com|language=en|access-date=2021-02-13}}</ref> Other common ingredients include: * ethyl (a form of alcohol), especially used in cough syrups * [[lactose]], which is common in many tablets * [[food coloring]]s, especially reds and blues<ref name="medicines" /> ===Brand names=== Diphenhydramine is marketed under many different brand names including: * Allermax * Banophen * Benadryl * Benylin Chesty Coughs Original and Benylin Mucus Cough Nights (syrup) * Compoz Nighttime Sleep Aid * Covonia Nighttime Forumla * Diphedryl or Diphenhis * Nytol One-A-Night * Nytol QuickCaps * QlearQuil Nightitme Allergy Relief * Siladryl Allergy * Silphen Cough * Sominex original * Tranquil * Twilite * Vanamine PD * Unisom Sleepgels maximum strength * Z-Sleep * ZzzQuil<ref name="drugscom" /><ref>{{Cite web | url = https://www.weldricks.co.uk/products/benylin-chesty-coughs-original-300ml | title = Β£8.59 - Benylin Chesty Coughs Original 300ml|website=Weldricks Pharmacy|language=en-GB|access-date=2021-02-12}}</ref><ref name="Covonia">{{Cite web | url = https://www.medicines.org.uk/emc/product/4832/smpc | title = Covonia Night Time Formula - Summary of Product Characteristics (SmPC) | last = | first = | authorlink = | date = | website = Electronic Medicines Compendium| archive-url = | archive-date = |url-status = | access-date=2021-02-13}}</ref> ==Theory== ==Evidence== Clinical trials of the effects of diphenhydramine on ME/CFS patients have not been conducted. ===Long COVID === Two female patients have been reported to have experienced rapid and significant improvements in their [[Long COVID]] symptoms after taking diphenhydramine, in particular in [[exercise intolerance|exercise tolerance]] and [[post-exertional malaise]]. The patients used doses of 50mg and 25mg of diphenhydramine respectively, with one of these patients also responding to 50mg [[hydroxyzine pamoate]].<ref name="Pinto2022" /> These effects did not occur using [[fexofenadine]].<ref name="Pinto2022" /> Pinto et al. (2022) stated that some COVID-19 patients had improved after [[:Category:Antihistamines|antihistamine]] treatment, and according to [[Natalie Lambert]], long covid patients in a [[Survivor Corps]] social media group has frequently posted about antihistamines. Glynne et al. (2022) also commented on anecdoteal reports of long COVID patients improving with antihistamines, and the role of [[histamine]] in COVID-19.<ref name="Glynne2022" /> Glynne et al. conducted a small observational study using a combination of H1 ([[loratadine]] or [[fexofenadine]]) and H2 ([[famotidine]] or [[nizatidine]] histamine receptor antagonists (HRAs) for a minimum of 4 weeks, finding clinically significant improvement in the majority of patients.<ref name="Glynne2022" /> ==Dosage== The usual dose suggested is: * creams for bites, itches or eczema - apply a thin layer once or twice a day * [[Allergy|allergies]] and [[hayfever]], itching or as an anti-histamine - 25mg to 25mg, 3 or 4 times a day * [[cough]] and cold symptoms β diphenhydramine is typically mixed with other medicines, the dose depends on the medicine * creams for bites, itches or eczema - apply a thin layer once or twice a day * [[Sleep dysfunction|sleep problems]] or [[insomnia]] - 25mg to 50mg<ref name="NHS" /> ==Risks and safety== Diphenhydramine has a wide range of side effects include [[dizziness]] and [[Daytime sleepiness|drowsiness]] (sedation), and is sometimes used for [[insomnia]].<ref name="drugscom" /> It is described as non-addictive/not habit forming, but recently concerns have been raised about long term use including the reduced effectiveness in the long term, causing people to increase the dose.<ref name="Theoharides2016">{{Cite journal| title = Antihistamine and mental status | date = 2016 | url=https://www.mastcellaware.com/media/articles/Antihistamines-mental-status-Jrnl-Clin-Pshychopharm-v36-3-2016.pdf | pmid= | last = Theoharides | last2 =Stewart | first2 =JM| first = TC|journal =J Clin Psychopharmacol|volume= 36 | issue= 3 | pages = 195-7 }}</ref> Theoharides and Stewart (2016) stated that in high risk over 65s taking 50mg for 3 years or 50mg for 3 years was associated with [[cognitive dysfunction]].<ref name="Theoharides2016" /> Using a product containing diphenhydramine marketed for nighttime pain, coughs or cold and flu, also involves the side effects of other active ingredients, or from inactive ingredients such as food colorings.<ref name="medicines" /><ref name="Covonia" /> ==Costs and availability== Diphenhydramine is available over the counter, under many different brand names including Benadryl.<ref name="drugscom" /> Diphenhydramine is available in tablet, capsule or syrup/liquid form, and in anti-histamine products as a cream, spray or ointment to be applied to the skin.<ref name="webmd">{{Cite web | url = https://www.webmd.com/drugs/2/drug-1428/diphenhydramine-oral/details | title = Diphenhydramine Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing | last = | first = | authorlink = | date = | website = WebMD|language=en| archive-url = | archive-date = |url-status = | access-date=2021-02-13}}</ref> In the UK, diphenhydramine is a pharmacy-only medication and is not given on prescription.<ref name="medicines" /> Diphenhydramine is available under the brand names Benylin Chesty Coughs, Histergan, and Nytol Once-A-Day.<ref name="NHS" /> ==Notable studies == *2022, Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines<ref name="Glynne2022">{{Cite journal | title = Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines | date = Jan 2022 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494538/|journal=Journal of Investigative Medicine|volume=70|issue=1 | pages = 61β67 | last = Glynne | first = Paul | authorlink = Paul Glynne | last2 = Tahmasebi | first2 = Natasha | authorlink2 = | last3 = Gant | first3 = Vanya | authorlink3 = | last4 = Gupta | first4 = Rajeev | authorlink4 = |doi=10.1136/jim-2021-002051|pmc=8494538|pmid=34611034|access-date=|issn=1081-5589|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494538/ (Full text)] *2022, Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection<ref name="Pinto2022">{{Cite journal | title = Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection | date = 2022-02-07 | url = https://www.npjournal.org/article/S1555-4155(21)00547-X/abstract|journal=The Journal for Nurse Practitioners|volume=0|issue=0 | pages = | last = Pinto | first = Melissa D. | authorlink = Melissa Pinto | last2 = Lambert | first2 = Natalie | authorlink2 = Natalie Lambert | last3 = Downs | first3 = Charles A. | authorlink3 = | last4 = Abrahim | first4 = Heather | authorlink4 = | last5 = Hughes | first5 = Thomas D. | author-link5 = | last6 = Rahmani | first6 = Amir M. | author-link6 = | last7 = Burton | first7 = Candace W. | last8 = Chakraborty | first8 = Rana|language=English|doi=10.1016/j.nurpra.2021.12.016|pmc=PMC8820139|pmid=35153633|access-date=|issn=1555-4155|quote=|via=}}</ref> - [https://doi.org/10.1016/j.nurpra.2021.12.016 (Full text)] ==See also== *[[Insomnia]] *[[Sleep dysfunction]] *[[Histamine]] ==Learn more== *[https://www.drugs.com/diphenhydramine.html Diphenhydramine] - drugs.com *[https://www.nhs.uk/medicines/diphenhydramine/ Diphenhydramine] - NHS *[https://www.webmd.com/drugs/2/drug-1428/diphenhydramine-oral/details Diphenhydramine] - WedMD ==References== {{reflist}} [[Category:Potential treatments]] [[Category:Sleep aids and hypnotics]] [[Category:Antihistamines]] [[Category:H1 antihistamines]] [[Category:Non-benzodiazepine hypnotics]] [[Category:Sedating antihistamines]]
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