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<!-- Clinical data -->| pronounce = {{IPAc-en|ˌ|d|aɪ|f|ɛ|n|ˈ|h|aɪ|d|r|ə|m|iː|n}}
| tradename = Sedares, Sominal, [[Benadryl]], Unisom, [[Nytol]], dll
| Drugs.com = {{drugs.com|monograph|diphenhydramine-hydrochloride}}
| MedlinePlus = a682539
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}}
'''Difenhidramin''' (Bahasa Inggris: '''''Diphenhydramine''''', disingkat '''DPH''')
Efek samping yang umum termasuk kantuk, koordinasi yang buruk, dan [[mulas]].<ref name=AHSP2016/> Penggunaannya tidak dianjurkan pada anak kecil atau orang tua.<ref name=AHSP2016/><ref name=schroeck2016>{{cite journal | vauthors = Schroeck JL, Ford J, Conway EL, Kurtzhalts KE, Gee ME, Vollmer KA, Mergenhagen KA | title = Review of Safety and Efficacy of Sleep Medicines in Older Adults | journal = Clinical Therapeutics | volume = 38 | issue = 11 | pages = 2340–2372 | date = November 2016 | pmid = 27751669 | doi = 10.1016/j.clinthera.2016.09.010 | doi-access = free }}</ref> Tidak ada risiko bahaya yang jelas bila digunakan selama kehamilan, sedangkan penggunaan selama menyusui tidak dianjurkan.<ref>{{cite web|title=Diphenhydramine Pregnancy and Breastfeeding Warnings|url=https://www.drugs.com/pregnancy/diphenhydramine.html|website=Drugs.com|access-date=28 September 2016|url-status=live|archive-url=https://web.archive.org/web/20161002114958/https://www.drugs.com/pregnancy/diphenhydramine.html|archive-date=2 October 2016}}</ref> Obat ini merupakan antihistamin H1 generasi pertama dan bekerja dengan memblokir efek [[histamin]] tertentu, yang menghasilkan efek antihistamin dan sedatifnya.<ref name=AHSP2016/><ref name="Saran2017"/> Difenhidramin juga merupakan [[antikolinergik]] yang kuat, yang berarti obat ini juga bekerja sebagai [[delirian]] pada dosis yang jauh lebih tinggi dari dosis yang dianjurkan.<ref>{{cite book| vauthors = Ayd FJ |title=Lexicon of Psychiatry, Neurology, and the Neurosciences|date=2000|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-2468-5 | page = 332 | url = https://books.google.com/books?id=ea_QVG2BFy8C&pg=PA332 | url-status = live | archive-url = https://web.archive.org/web/20170908214041/https://books.google.ca/books?id=ea_QVG2BFy8C&pg=PA332 | archive-date = 8 September 2017}}</ref> Efek sedatif dan deliriannya telah menyebabkan beberapa kasus [[penggunaan zat adiktif]].<ref name="Thomas2008"/><ref name="Saran2017">{{cite journal | vauthors = Saran JS, Barbano RL, Schult R, Wiegand TJ, Selioutski O | title = Chronic diphenhydramine abuse and withdrawal: A diagnostic challenge | journal = Neurology. Clinical Practice | volume = 7 | issue = 5 | pages = 439–441 | date = October 2017 | pmid = 29620065 | pmc = 5874453 | doi = 10.1212/CPJ.0000000000000304}}</ref>
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[[File:Benadryl tablets (4438315926).jpg|thumb|left|Difenhidramin tablet]]
Difenhidramin adalah antihistamin generasi pertama yang digunakan untuk mengobati sejumlah kondisi termasuk gejala alergi dan [[gatal]]-gatal, [[pilek]], insomnia, [[mabuk gerak]], dan gejala ekstrapiramidal.<ref name="AHFS_monograph">{{cite web | url = https://www.drugs.com/monograph/diphenhydramine-hydrochloride.html | title = Diphenhydramine Hydrochloride Monograph | publisher = The American Society of Health-System Pharmacists | work = Drugs.com | url-status = live | archive-url = https://web.archive.org/web/20110615135322/http://www.drugs.com/monograph/diphenhydramine-hydrochloride.html | archive-date = 15 June 2011 | df = dmy-all }}</ref><ref name="Brown_2012">{{cite journal|vauthors=Brown HE, Stoklosa J, Freudenreich O |title=How to stabilize an acutely psychotic patient |journal=Current Psychiatary |volume=11 |issue=12 |pages=10–16 |date=December 2012 |url=http://stg.currentpsychiatry.com/pdf/1112/1112CP_Freudenreich.pdf |url-status=dead |archive-url=https://web.archive.org/web/20130514183445/http://stg.currentpsychiatry.com/pdf/1112/1112CP_Freudenreich.pdf |archive-date=14 May 2013 }}</ref> Difenhidramin juga memiliki sifat [[anestesi lokal]], dan telah digunakan pada orang yang alergi terhadap anestesi lokal umum seperti [[lidokain]].<ref name="pmid10456039">{{cite journal | vauthors = Smith DW, Peterson MR, DeBerard SC | title = Local anesthesia. Topical application, local infiltration, and field block | url = https://archive.org/details/sim_postgraduate-medicine_1999-08_106_2/page/57 | journal = Postgraduate Medicine | volume = 106 | issue = 2 | pages = 57–60, 64–6 | date = August 1999 | pmid = 10456039 | doi = 10.3810/pgm.1999.08.650 }}</ref>
===Alergi===
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Melalui suntikan, obat ini sering digunakan selain [[epinefrin]] untuk mengobati [[anafilaksis]],<ref name="Current EM">{{cite book | veditors = Humphries RL, Stone CK | title = CURRENT Diagnosis and Treatment Emergency Medicine | edition = Seventh | series = LANGE CURRENT Series | publisher = McGraw–Hill Professional | year = 2011 | isbn = 978-0-07-170107-5 | chapter = Chapter 11: Shock | vauthors = Young WF }}</ref> meskipun pada tahun 2007 penggunaannya untuk tujuan tersebut belum diteliti dengan baik.<ref name=Cochrane2007rev>{{cite journal | vauthors = Sheikh A, ten Broek VM, Brown SG, Simons FE | title = H1-antihistamines for the treatment of anaphylaxis with and without shock | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD006160 | date = January 2007 | volume = 2007 | pmid = 17253584 | doi = 10.1002/14651858.CD006160.pub2 | pmc = 6517288 }}</ref> Penggunaannya hanya dianjurkan ketika gejala akut sudah membaik.<ref name=AHSF2016/>
Tersedia formulasi topikal difenhidramin termasuk krim, losion, gel, dan semprotan. Obat ini digunakan untuk menghilangkan rasa gatal dan memiliki keuntungan karena menyebabkan efek sistemik yang lebih sedikit (mis: mengantuk) dibandingkan bentuk [[Oral (rute pemberian obat)|oral]].<ref>{{Cite web|title=Diphenhydramine Topical|url=https://medlineplus.gov/druginfo/meds/a601044.html|access-date=9 October 2020|website=[[MedlinePlus]]|archive-date=10 October 2020|archive-url=https://web.archive.org/web/20201010221833/https://medlineplus.gov/druginfo/meds/a601044.html|url-status=live}}</ref>
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===Obat Tidur===
Karena sifat sedatifnya, difenhidramin banyak digunakan dalam obat tidur tanpa resep untuk mengatasi [[insomnia]]. Obat tersebut merupakan bahan dalam beberapa produk yang dijual sebagai alat bantu tidur, baik sendiri maupun dikombinasikan dengan obat lain seperti [[parasetamol]] pada Tylenol PM dan [[ibuprofen]] pada Advil PM. Difenhidramin dapat menyebabkan ketergantungan psikologis ringan.<ref>{{cite web|url=http://allergies.emedtv.com/benadryl/benadryl-addiction.html|title=Benadryl Addiction|publisher=eMedTV| vauthors = Monson K, Schoenstadt A | date = 8 September 2013 | url-status = live | archive-url = https://web.archive.org/web/20140104053402/http://allergies.emedtv.com/benadryl/benadryl-addiction.html | archive-date = 4 January 2014 | df = dmy-all }}</ref> Difenhidramin juga telah digunakan sebagai [[anksiolitik]].<ref name="Dinndroff_1998">{{cite journal | vauthors = Dinndorf PA, McCabe MA, Friedrich S | title = Risk of abuse of diphenhydramine in children and adolescents with chronic illnesses | url = https://archive.org/details/sim_journal-of-pediatrics_1998-08_133_2/page/293 | journal = The Journal of Pediatrics | volume = 133 | issue = 2 | pages = 293–5 | date = August 1998 | pmid = 9709726 | doi = 10.1016/S0022-3476(98)70240-9}}</ref>
Difenhidramin juga telah digunakan tanpa resep oleh orang tua dalam upaya membuat anak-anak mereka tidur dan membius mereka dalam penerbangan jarak jauh.<ref>{{Cite news|url=https://www.telegraph.co.uk/travel/family-holidays/is-it-ok-drug-babies-toddlers-children-sleep-flight-antihistamines/ |archive-url=https://ghostarchive.org/archive/20220111/https://www.telegraph.co.uk/travel/family-holidays/is-it-ok-drug-babies-toddlers-children-sleep-flight-antihistamines/ |archive-date=11 January 2022 |url-access=subscription |url-status=live|title=Is it wrong to drug your children so they sleep on a flight?| vauthors = Crier F |website=The Telegraph|date=2 August 2017|access-date=13 April 2020}}{{cbignore}}</ref> Hal ini mendapat kritik, baik dari dokter maupun anggota industri penerbangan, karena pemberian obat penenang pada penumpang dapat menempatkan mereka pada risiko jika mereka tidak dapat bereaksi secara efisien terhadap keadaan darurat,<ref>{{Cite news|vauthors=Morris R|url=https://www.bbc.com/news/magazine-21977785|title=Should parents drug babies on long flights?|date=3 April 2013|work=BBC News|access-date=13 April 2020|archive-date=8 March 2021|archive-url=https://web.archive.org/web/20210308034544/https://www.bbc.com/news/magazine-21977785|url-status=live}}</ref> dan karena efek samping obat, terutama kemungkinan terjadinya paradoks. reaksi, mungkin membuat beberapa pengguna menjadi [[Gangguan pemusatan perhatian dan hiperaktivitas|hiperaktif]]. Untuk mengatasi penggunaan obat tersebut, Rumah Sakit Anak [[Seattle]] berargumentasi dalam sebuah artikel tahun 2009, "Menggunakan obat demi kenyamanan Anda tidak pernah menjadi indikasi pemberian obat pada anak."<ref>{{Cite web |vauthors=Swanson WS |date=25 November 2009 |title=If It Were My Child: No Benadryl for the Plane |url=https://seattlemamadoc.seattlechildrens.org/if-it-were-my-child-no-benadryl-for-the-plane/ |publisher=Seattle Children's |access-date=13 April 2020 |archive-date=25 February 2021 |archive-url=https://web.archive.org/web/20210225070641/https://seattlemamadoc.seattlechildrens.org/if-it-were-my-child-no-benadryl-for-the-plane/ |url-status=dead }}</ref>
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===Mual===
===Populasi Khusus===
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==Efek Samping==
Efek samping yang paling menonjol adalah sedasi. Dosis tipikal menyebabkan gangguan mengemudi yang setara dengan kadar alkohol dalam darah 0,10; yang lebih tinggi dari batas 0,08 dalam sebagian besar undang-undang mengemudi dalam keadaan mabuk.<ref name=2007rev/>
Difenhidramin adalah agen [[antikolinergik]] yang kuat dan berpotensi delirian pada dosis yang lebih tinggi. Aktivitas ini bertanggung jawab atas efek samping mulut dan tenggorokan kering, [[takikardia]], pelebaran pupil, [[retensi urin]], [[sembelit]], dan pada dosis tinggi halusinasi atau [[delirium]]. Efek samping lainnya termasuk gangguan motorik ([[ataksia]]), kulit memerah, penglihatan kabur pada titik dekat karena kurangnya akomodasi (sikloplegia), sensitivitas abnormal terhadap cahaya terang ([[fotofobia]]), sedasi, sulit berkonsentrasi, [[amnesia]], gangguan penglihatan, ketidakteraturan [[pernapasan]], pusing, [[iritabilitas]], kulit gatal, kebingungan, peningkatan suhu tubuh (umumnya di tangan dan/atau kaki), [[disfungsi ereksi]] sementara dan rangsangan, dan meskipun dapat digunakan untuk mengobati mual dosis yang lebih tinggi dapat menyebabkan muntah. <ref name="diph effects">{{cite web | url = https://www.drugs.com/sfx/diphenhydramine-side-effects.html | title = Diphenhydramine Side Effects | publisher = Drugs.com | access-date = 6 April 2009 | url-status = live | archive-url = https://web.archive.org/web/20090124235224/http://www.drugs.com/sfx/diphenhydramine-side-effects.html | archive-date = 24 January 2009 | df = dmy-all }}</ref> Difenhidramin dalam overdosis kadang-kadang dapat menyebabkan perpanjangan interval QT.<ref>{{cite book |vauthors=Aronson JK |title=Meyler's Side Effects of Cardiovascular Drugs |date=2009 |publisher=Elsevier |isbn=978-0-08-093289-7 |page=623 |url=https://books.google.com/books?id=oeBgU3UwgZkC&dq=Diphenhydramine+QT+prolongation&pg=PA623 |access-date=4 March 2020 |archive-date=8 March 2021 |archive-url=https://web.archive.org/web/20210308005242/https://www.google.com/books/edition/Meyler_s_Side_Effects_of_Cardiovascular/oeBgU3UwgZkC?hl=en&gbpv=1&dq=Diphenhydramine+QT+prolongation&pg=PA623 |url-status=live}}</ref>
Beberapa orang mengalami reaksi alergi terhadap difenhidramin berupa [[urtikaria]].<ref name="pmid9007386">{{cite journal | vauthors = Heine A | title = Diphenhydramine: a forgotten allergen? | journal = Contact Dermatitis | volume = 35 | issue = 5 | pages = 311–312 | date = November 1996 | pmid = 9007386 | doi = 10.1111/j.1600-0536.1996.tb02402.x | s2cid = 32839996}}</ref><ref name="pmid6219138">{{cite journal | vauthors = Coskey RJ | title = Contact dermatitis caused by diphenhydramine hydrochloride | journal = Journal of the American Academy of Dermatology | volume = 8 | issue = 2 | pages = 204–206 | date = February 1983 | pmid = 6219138 | doi = 10.1016/S0190-9622(83)70024-1}}</ref>
Kondisi seperti kegelisahan atau akatisia dapat memburuk akibat peningkatan kadar difenhidramin, terutama dengan dosis rekreasional.<ref name="pmid18227744">{{cite journal | vauthors = de Leon J, Nikoloff DM | title = Paradoxical excitation on diphenhydramine may be associated with being a CYP2D6 ultrarapid metabolizer: three case reports | journal = CNS Spectrums | volume = 13 | issue = 2 | pages = 133–5 | date = February 2008 | pmid = 18227744 | doi = 10.1017/s109285290001628x| s2cid = 10856872 }}</ref> Difenhidramin dalam dosis normal, seperti antihistamin generasi pertama lainnya, juga dapat memperburuk gejala sindrom kaki gelisah.<ref>{{cite web |title=Restless Legs Syndrome Fact Sheet |website=National Institute of Neurological Disorders and Stroke |url=https://www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/restless-legs-syndrome-fact-sheet |access-date=27 August 2019 |archive-date=28 July 2017 |archive-url=https://web.archive.org/web/20170728021833/https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Restless-Legs-Syndrome-Fact-Sheet |url-status=live }}</ref> Karena difenhidramin dimetabolisme secara ekstensif di hati, kehati-hatian harus dilakukan saat memberikan obat kepada individu dengan gangguan hati.
Penggunaan [[antikolinergik]] di kemudian hari dikaitkan dengan peningkatan risiko penurunan kognitif dan demensia pada orang lanjut usia.<ref>{{cite journal | vauthors = Salahudeen MS, Duffull SB, Nishtala PS | title = Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review | journal = BMC Geriatrics | volume = 15 | issue = 31 | pages = 31 | date = March 2015 | pmid = 25879993 | pmc = 4377853 | doi = 10.1186/s12877-015-0029-9 | df = dmy-all | doi-access = free }}</ref>
==Kontraindikasi==
Difenhidramin dikontraindikasikan pada bayi prematur dan neonatus, serta orang yang sedang menyusui. Difenhidramin adalah obat kehamilan Kategori B. Difenhidramin memiliki efek aditif dengan alkohol dan depresan SSP lainnya. Penghambat oksidase monoamine memperpanjang dan mengintensifkan efek [[antikolinergik]] antihistamin.<ref>{{cite book |vauthors=Sicari V, Zabbo CP |chapter=Diphenhydramine |date=2021 |url=http://www.ncbi.nlm.nih.gov/books/NBK526010/ |title=StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30252266 |access-date=27 December 2021 |archive-date=28 May 2022 |archive-url=https://web.archive.org/web/20220528171459/https://www.ncbi.nlm.nih.gov/books/NBK526010/ |url-status=live }}</ref>
==Overdosis==
Difenhidramin adalah salah satu obat bebas yang paling sering disalahgunakan di Amerika Serikat.<ref name="pmid32491510">{{cite book| vauthors = Huynh DA, Abbas M, Dabaja A | pmid = 32491510 | title=Diphenhydramine Toxicity| year = 2021 }}</ref> Dalam kasus overdosis ekstrem, jika tidak ditangani tepat waktu, keracunan difenhidramin akut dapat menimbulkan konsekuensi serius dan berpotensi fatal. Gejala overdosis mungkin termasuk:<ref name="urlDiphenhydramine overdose: MedlinePlus Medical Encyclopedia">{{cite encyclopedia | url = https://www.nlm.nih.gov/medlineplus/ency/article/002636.htm | title = Diphenhydramine overdose | encyclopedia = MedlinePlus Medical Encyclopedia | publisher = U.S. National Library of Medicine | url-status = live | archive-url = https://web.archive.org/web/20130530074604/http://www.nlm.nih.gov/medlineplus/ency/article/002636.htm | archive-date = 30 May 2013 | df = dmy-all }}</ref>
*Sakit perut
*Ucapan tidak normal (tidak terdengar, ucapan yang dipaksakan, dll.)
*[[Megakolon]] akut
*[[Kegelisahan]]/gugup
*[[Koma]]
*Kematian
*Delirium
*Disorientasi mental
*[[Disosiasi]]
*[[Euforia]] atau [[disforia]]
*Rasa kantuk yang luar biasa
*Kulit memerah
*[[Halusinasi]] (pendengaran, visual, sentuhan, dll.)
*[[Palpitasi]] jantung
*Ketidakmampuan untuk buang air kecil
*Gangguan motorik
*[[Spasmofili]] otot
*[[Sawan]]
*Pusing parah
*[[Xerostomia]] parah
*Tremor
*Muntah
Keracunan akut bisa berakibat fatal, menyebabkan kolaps kardiovaskular dan kematian dalam 2–18 jam, dan secara umum ditangani dengan pendekatan simtomatik dan suportif.<ref name="Goodman"/> Diagnosis toksisitas didasarkan pada riwayat dan gambaran klinis, dan secara umum kadar plasma yang tepat tampaknya tidak memberikan informasi klinis relevan yang berguna.<ref name="Poisoning&Overdoses">{{cite book | vauthors = Manning B | veditors = Olson K | title = Poisoning & Drug Overdose | chapter-url = http://www.accessmedicine.com/content.aspx?aID=55974020. | access-date = 19 March 2013 | edition = 6th | year = 2012 | publisher = McGraw-Hill | isbn = 978-0-07-166833-0 | chapter = Chapter 18. Antihistamines}}</ref> Beberapa tingkat bukti kuat menunjukkan difenhidramin (mirip dengan [[klorfenamin]]) dapat memblokir [[saluran kalium]] yang tertunda, dan sebagai konsekuensinya memperpanjang interval QT, menyebabkan [[aritmia]] jantung seperti ''[[torsade de pointes]]''.<ref>{{cite journal | vauthors = Khalifa M, Drolet B, Daleau P, Lefez C, Gilbert M, Plante S, O'Hara GE, Gleeton O, Hamelin BA, Turgeon J | title = Block of potassium currents in guinea pig ventricular myocytes and lengthening of cardiac repolarization in man by the histamine H1 receptor antagonist diphenhydramine | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 288 | issue = 2 | pages = 858–65 | date = February 1999 | pmid = 9918600 }}</ref> Tidak ada obat [[antidot]] spesifik untuk toksisitas difenhidramin yang diketahui, namun sindrom antikolinergik telah diobati dengan fisostigmin untuk [[delirium]] parah atau [[takikardia]].<ref name="Poisoning&Overdoses"/> [[Benzodiazepin]] dapat diberikan untuk mengurangi kemungkinan [[psikosis]], agitasi, dan [[sawan]] pada orang yang rentan terhadap gejala-gejala ini.<ref>{{cite journal | vauthors = Cole JB, Stellpflug SJ, Gross EA, Smith SW | title = Wide complex tachycardia in a pediatric diphenhydramine overdose treated with sodium bicarbonate | journal = Pediatric Emergency Care | volume = 27 | issue = 12 | pages = 1175–7 | date = December 2011 | pmid = 22158278 | doi = 10.1097/PEC.0b013e31823b0e47 | s2cid = 5602304 }}</ref>
==Interaksi==
Alkohol dapat meningkatkan rasa kantuk yang disebabkan oleh difenhidramin.<ref name="urlDiphenhydramine and Alcohol / Food Interactions - Drugs.com">{{cite web | url = https://www.drugs.com/food-interactions/diphenhydramine.html | title = Diphenhydramine and Alcohol / Food Interactions | publisher = Drugs.com | url-status = live | archive-url = https://web.archive.org/web/20130217152320/http://www.drugs.com/food-interactions/diphenhydramine.html | archive-date = 17 February 2013 | df = dmy-all }}</ref><ref name="pmid10344773">{{cite journal | vauthors = Zimatkin SM, Anichtchik OV | title = Alcohol-histamine interactions | journal = Alcohol and Alcoholism | volume = 34 | issue = 2 | pages = 141–7 | year = 1999 | pmid = 10344773 | doi = 10.1093/alcalc/34.2.141 | doi-access = free }}</ref>
==Farmakologi==
===Farmakodinamik===
{| class="wikitable floatright" style="font-size:small;"
|+ <br />Difenhidramin<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP) | vauthors = Roth BL, Driscol J | author1-link = Bryan Roth | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=diphenhydramine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | archive-date = 20 April 2019 | archive-url = https://web.archive.org/web/20190420130325/https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=diphenhydramine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | url-status = live }}</ref>
|-
! Lokasi !! K<sub>i</sub> (nM) !! Tempat !! Referensi
|-
| {{abbrlink|SERT|Pengangkut serotonin}} || ≥3,800 || Manusia || <ref name="pmid9537821">{{cite journal | vauthors = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = European Journal of Pharmacology | volume = 340 | issue = 2–3 | pages = 249–58 | date = December 1997 | pmid = 9537821 | doi = 10.1016/s0014-2999(97)01393-9 }}</ref><ref name="pmid23357028">{{cite journal | vauthors = Krystal AD, Richelson E, Roth T | title = Review of the histamine system and the clinical effects of H1 antagonists: basis for a new model for understanding the effects of insomnia medications | journal = Sleep Medicine Reviews | volume = 17 | issue = 4 | pages = 263–72 | date = August 2013 | pmid = 23357028 | doi = 10.1016/j.smrv.2012.08.001 }}</ref>
|-
| {{abbrlink|NET|Pengangkut norepinefrin}} || 960–2,400 || Manusia || <ref name="pmid9537821" /><ref name="pmid23357028" />
|-
| {{abbrlink|DAT|Pengangkut dopamin}} || 1,100–2,200 || Manusia || <ref name="pmid9537821" /><ref name="pmid23357028" />
|-
| [[Reseptor 5-HT2C|5-HT<sub>2C</sub>]] || 780 || Manusia || <ref name="pmid23357028" />
|-
| [[Reseptor alfa-1B adrenergik|α<sub>1B</sub>]] || 1,300 || Manusia || <ref name="pmid23357028" />
|-
| [[Reseptor alfa-2A adrenergik|α<sub>2A</sub>]] || 2,900 || Manusia || <ref name="pmid23357028" />
|-
| [[Reseptor alfa-2B adrenergik|α<sub>2B</sub>]] || 1,600 || Manusia || <ref name="pmid23357028" />
|-
| [[Reseptor alfa-2C adrenergik|α<sub>2C</sub>]] || 2,100 || Manusia || <ref name="pmid23357028" />
|-
| [[Reseptor D2|D<sub>2</sub>]] || 20,000 || Tikus besar || <ref name="pmid1361536">{{cite journal | vauthors = Tsuchihashi H, Sasaki T, Kojima S, Nagatomo T | title = Binding of [3H]haloperidol to dopamine D2 receptors in the rat striatum | journal = J. Pharm. Pharmacol. | volume = 44 | issue = 11 | pages = 911–4 | year = 1992 | pmid = 1361536 | doi = 10.1111/j.2042-7158.1992.tb03235.x| s2cid = 19420332 }}</ref>
|-
| [[Reseptor histamin H1|H<sub>1</sub>]] || 9.6–16 || Manusia || <ref name="pmid">{{cite journal | vauthors = Ghoneim OM, Legere JA, Golbraikh A, Tropsha A, Booth RG | title = Novel ligands for the human histamine H1 receptor: synthesis, pharmacology, and comparative molecular field analysis studies of 2-dimethylamino-5-(6)-phenyl-1,2,3,4-tetrahydronaphthalenes | journal = Bioorganic & Medicinal Chemistry | volume = 14 | issue = 19 | pages = 6640–58 | date = October 2006 | pmid = 16782354| doi = 10.1016/j.bmc.2006.05.077 }}</ref><ref name="pmid23357028" />
|-
| [[Reseptor histamin H2|H<sub>2</sub>]] || >100,000 || [[Canidae|Canine]] || <ref name="pmid1703298">{{cite journal | vauthors = Gantz I, Schäffer M, DelValle J, Logsdon C, Campbell V, Uhler M, Yamada T | title = Molecular cloning of a gene encoding the histamine H2 receptor | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 2 | pages = 429–33 | year = 1991 | pmid = 1703298 | pmc = 50824 | doi = 10.1073/pnas.88.2.429| bibcode = 1991PNAS...88..429G | doi-access = free }}</ref>
|-
| [[Reseptor histamin H3|H<sub>3</sub>]] || >10,000 || Manusia || <ref name="pmid23357028" /><ref name="pmid10347254">{{cite journal | vauthors = Lovenberg TW, Roland BL, Wilson SJ, Jiang X, Pyati J, Huvar A, Jackson MR, Erlander MG | title = Cloning and functional expression of the human histamine H3 receptor | journal = Molecular Pharmacology | volume = 55 | issue = 6 | pages = 1101–7 | date = June 1999 | pmid = 10347254 | doi = 10.1124/mol.55.6.1101| s2cid = 25542667 }}</ref><ref name="pmid11179434">{{cite journal | vauthors = Liu C, Ma X, Jiang X, Wilson SJ, Hofstra CL, Blevitt J, Pyati J, Li X, Chai W, Carruthers N, Lovenberg TW | title = Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow | journal = Molecular Pharmacology | volume = 59 | issue = 3 | pages = 420–6 | date = March 2001 | pmid = 11179434 | doi = 10.1124/mol.59.3.420 | s2cid = 123619 }}</ref>
|-
| [[Reseptor histamin H4|H<sub>4</sub>]] || >10,000 || Manusia || <ref name="pmid11179434" />
|-
| [[Reseptor asetilkolin muskarinik M1|M<sub>1</sub>]] || 80–100 || Manusia || <ref name="pmid1346637">{{cite journal | vauthors = Bolden C, Cusack B, Richelson E | title = Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 260 | issue = 2 | pages = 576–80 | date = February 1992 | pmid = 1346637 }}</ref><ref name="pmid23357028" />
|-
| [[Reseptor asetilkolin muskarinik M2|M<sub>2</sub>]] || 120–490 || Manusia || <ref name="pmid1346637" /><ref name="pmid23357028" />
|-
| [[Reseptor asetilkolin muskarinik M3|M<sub>3</sub>]] || 84–229 || Manusia || <ref name="pmid1346637" /><ref name="pmid23357028" />
|-
| [[Reseptor asetilkolin muskarinik M4|M<sub>4</sub>]] || 53–112 || Manusia || <ref name="pmid1346637" /><ref name="pmid23357028" />
|-
| [[Reseptor asetilkolin muskarinik M5|M<sub>5</sub>]] || 30–260 || Manusia || <ref name="pmid1346637" /><ref name="pmid23357028" />
|-
| {{abbrlink|VGSC|Saluran natrium yang bergantung pada tegangan}} || 48,000–86,000 || Tikus besar || <ref name="pmid11036158" />
|-
| {{abbrlink|hERG|Gen Terkait Eter-à-go-go Manusia}} || 27,100 ({{abbrlink|IC<sub>50</sub>|Half-maximal inhibitory concentration}}) || Manusia || <ref name="pmid8641472">{{cite journal | vauthors = Suessbrich H, Waldegger S, Lang F, Busch AE | title = Blockade of HERG channels expressed in Xenopus oocytes by the histamine receptor antagonists terfenadine and astemizole | journal = FEBS Letters | volume = 385 | issue = 1–2 | pages = 77–80 | date = April 1996 | pmid = 8641472 | doi = 10.1016/0014-5793(96)00355-9 | s2cid = 40355762 | doi-access = free }}</ref>
|- class="sortbottom"
| colspan="4" style="width: 1px;" | Nilainya adalah K<sub>i</sub> (nM), kecuali dinyatakan lain. Semakin kecil nilainya, semakin kuat obat tersebut berikatan dengan situs tersebut.
|}
Difenhidramin, tersedia dalam berbagai bentuk garam,<ref>{{cite journal | vauthors = Wang C, Paul S, Wang K, Hu S, Sun CC | title=Relationships among Crystal Structures, Mechanical Properties, and Tableting Performance Probed Using Four Salts of Diphenhydramine | date=2017 | journal=Crystal Growth & Design | volume=17 | issue=11 | pages=6030–6040 | doi=10.1021/acs.cgd.7b01153 }}</ref> seperti sitrat,<ref>{{cite journal | vauthors = Rao DD, Venkat Rao P, Sait SS, Mukkanti K, Chakole D | title=Simultaneous Determination of Ibuprofen and Diphenhydramine Citrate in Tablets by Validated LC | date=2009 | journal=Chromatographia | volume=69 | issue=9–10 | pages=1133–1136 | s2cid=97766056 | doi=10.1365/s10337-009-0977-3 }}</ref><ref>{{cite journal | vauthors = Rao DD, Sait SS, Mukkanti K | title=Development and Validation of an UPLC Method for Rapid Determination of Ibuprofen and Diphenhydramine Citrate in the Presence of Impurities in Combined Dosage Form | date=2011 | journal=Journal of Chromatographic Science | volume=49 | issue=4 | pages=281–286 | pmid=21439118 | doi=10.1093/chrsci/49.4.281 }}</ref> hidroklorida,<ref>{{cite journal | vauthors = Chan CY, Wallander KA | title = Diphenhydramine toxicity in three children with varicella-zoster infection | journal = Dicp | volume = 25 | issue = 2 | pages = 130–132 | date = February 1991 | pmid = 2058184 | doi = 10.1177/106002809102500204 | s2cid = 45456788 }}</ref> dan salisilat,<ref>{{cite journal | vauthors = Kamijo Y, Soma K, Sato C, Kurihara K | title = Fatal diphenhydramine poisoning with increased vascular permeability including late pulmonary congestion refractory to percutaneous cardiovascular support | journal = Clinical Toxicology | volume = 46 | issue = 9 | pages = 864–868 | date = November 2008 | pmid = 18608279 | doi = 10.1080/15563650802116151 | s2cid = 43642257 }}</ref> menunjukkan berat molekul dan sifat [[farmakokinetik]] yang berbeda. Secara khusus, difenhidramin hidroklorida dan difenhidramin sitrat memiliki berat molekul masing-masing 291,8 g/mol<ref name="pubchem8980">{{cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/8980 | title=Diphenhydramine Hydrochloride | work = PubChem | publisher = U.S. National Library of Medicine }}</ref> dan 447,5 g/mol.<ref name="pubchem174697">{{cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/174697 | title=Diphenhydramine citrate | work = PubChem | publisher = U.S. National Library of Medicine }}</ref> Variasi berat molekul ini mempengaruhi laju disolusi dan karakteristik penyerapan masing-masing bentuk garam. Akibatnya, dosis 25 mg difenhidramin hidroklorida secara terapeutik setara dengan 38 mg difenhidramin sitrat. Oleh karena itu, penyesuaian dosis diperlukan untuk memperhitungkan perbedaan ini ketika beralih antar bentuk garam.<ref name="salts-drugs-com">{{cite web | vauthors = Pope C | date = 28 August 2023 | url=https://www.drugs.com/medical-answers/difference-between-diphenhydramine-hydrochloride-3510045/ | title=Diphenhydramine Hydrochloride vs Citrate: What's the difference? | work = drugs.com }}</ref>
Meskipun secara tradisional dikenal sebagai [[antagonis reseptor]], difenhidramin bertindak terutama sebagai agonis kebalikan dari reseptor histamin H1.<ref name="pmid22021988">{{cite journal | vauthors = Khilnani G, Khilnani AK | title = Inverse agonism and its therapeutic significance | journal = Indian Journal of Pharmacology | volume = 43 | issue = 5 | pages = 492–501 | date = September 2011 | pmid = 22021988 | pmc = 3195115 | doi = 10.4103/0253-7613.84947 | doi-access = free }}</ref> Obat ini adalah anggota dari kelas agen antihistaminergik [[etanolamina]].<ref name="Goodman">{{cite book |vauthors=Brunton L, Chabner B, Knollmann B | veditors = Brunton L | title = Goodman & Gilman's The Pharmacological Basis of Therapeutics |url=https://archive.org/details/goodmangilmansph0000unse_z2e0 | edition = 12e | year = 2011 | publisher = McGraw Hill | isbn = 978-0-07-162442-8 | pages = [https://archive.org/details/goodmangilmansph0000unse_z2e0/page/242 242]–245 | chapter = Chapter 32. Histamine, Bradykinin, and Their Antagonists }}</ref> Dengan membalikkan efek histamin pada [[pembuluh kapiler]], dapat mengurangi intensitas gejala alergi. Ia juga melintasi [[sawar darah otak]] dan berbanding terbalik dengan reseptor H1 di [[sistem saraf pusat]].<ref name="pmid22021988"/> Efeknya pada reseptor H1 sentral menyebabkan kantuk.
Difenhidramin adalah [[antimuskarinik]] yang kuat (antagonis kompetitif reseptor asetilkolin muskarinik), dan dengan demikian pada dosis tinggi dapat menyebabkan sindrom [[antikolinergik]].<ref name="urlAntihistamine Toxicity">{{cite web | url = http://emedicine.medscape.com/article/812828-overview | vauthors = Lopez AM | title = Antihistamine Toxicity | publisher = WebMD LLC | work = Medscape Reference | date = 10 May 2010 | url-status = live | archive-url = https://web.archive.org/web/20101013230957/http://emedicine.medscape.com/article/812828-overview | archive-date = 13 October 2010 | df = dmy-all }}</ref> Kegunaan difenhidramin sebagai agen antiparkinson adalah hasil dari sifat penghambatannya pada reseptor asetilkolin muskarinik di otak.
Difenhidramin juga bertindak sebagai penghambat saluran natrium intraseluler, yang bertanggung jawab atas tindakannya sebagai [[anestesi lokal]].<ref name="pmid11036158">{{cite journal | vauthors = Kim YS, Shin YK, Lee C, Song J | title = Block of sodium currents in rat dorsal root ganglion neurons by diphenhydramine | journal = Brain Research | volume = 881 | issue = 2 | pages = 190–8 | date = October 2000 | pmid = 11036158 | doi = 10.1016/S0006-8993(00)02860-2 | s2cid = 18560451 }}</ref> Difenhidramin juga telah terbukti menghambat pengambilan kembali [[serotonin]].<ref name="Domino_1999"/> Telah terbukti menjadi potensiator analgesia yang diinduksi oleh [[morfin]], namun tidak oleh opioid endogen pada tikus besar.<ref name="pmid2860599">{{cite journal | vauthors = Carr KD, Hiller JM, Simon EJ | title = Diphenhydramine potentiates narcotic but not endogenous opioid analgesia | journal = Neuropeptides | volume = 5 | issue = 4–6 | pages = 411–4 | date = February 1985 | pmid = 2860599 | doi = 10.1016/0143-4179(85)90041-1 | s2cid = 45054719 }}</ref> Obat ini juga ditemukan bertindak sebagai penghambat histamin N-metiltransferase (HNMT).<ref name="pmid16168438">{{cite journal | vauthors = Horton JR, Sawada K, Nishibori M, Cheng X | title = Structural basis for inhibition of histamine N-methyltransferase by diverse drugs | journal = Journal of Molecular Biology | volume = 353 | issue = 2 | pages = 334–344 | date = October 2005 | pmid = 16168438 | pmc = 4021489 | doi = 10.1016/j.jmb.2005.08.040 }}</ref><ref name="pmid4402747">{{cite journal | vauthors = Taylor KM, Snyder SH | title = Histamine methyltransferase: inhibition and potentiation by antihistamines | journal = Molecular Pharmacology | volume = 8 | issue = 3 | pages = 300–10 | date = May 1972 | pmid = 4402747 }}</ref>
{| class="wikitable"
|+ Ikhtisar target dan efek difenhidramin
|-
! Target biologi !! Mode aksi !! Efek
|-
| Reseptor H<sub>1</sub> || Agonis terbalik || Pengurangan alergi; Sedasi
|-
| Reseptor asetilkolin muskarinik || Antagonis
|| [[Antikolinergik]]; Antiparkinson
|-
| Saluran natrium || Penghambat || [[Anestesi lokal]]
|}
===Farmakokinetik===
[[Bioavailabilitas]] oral difenhidramin berada pada kisaran 40% hingga 60%, dan konsentrasi plasma puncak terjadi sekitar 2 hingga 3 jam setelah pemberian.<ref name="pmid2866055">{{cite journal | vauthors = Paton DM, Webster DR | title = Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines) | journal = Clinical Pharmacokinetics | volume = 10 | issue = 6 | pages = 477–97 | year = 1985 | pmid = 2866055 | doi = 10.2165/00003088-198510060-00002 | s2cid = 33541001 }}</ref>
Rute utama metabolisme adalah dua demetilasi berturut-turut dari [[amina]] tersier. Amina primer yang dihasilkan selanjutnya di[[Redoks|oksidasi]] menjadi [[asam karboksilat]].<ref name="pmid2866055"/> Difenhidramin dimetabolisme oleh [[enzim]] [[sitokrom P450]] [[Sitokrom P450 2D6|CYP2D6]], CYP1A2, CYP2C9, dan CYP2C19.<ref name="pmid19153052">{{cite journal | vauthors = Krystal AD | title = A compendium of placebo-controlled trials of the risks/benefits of pharmacological treatments for insomnia: the empirical basis for U.S. clinical practice | journal = Sleep Med Rev | volume = 13 | issue = 4 | pages = 265–74 | date = August 2009 | pmid = 19153052 | doi = 10.1016/j.smrv.2008.08.001 | url = }}</ref>
Waktu paruh eliminasi difenhidramin belum sepenuhnya diketahui, namun tampaknya berkisar antara 2,4 dan 9,3 jam pada orang dewasa yang sehat.<ref name="AHFS">{{cite book|title=AHFS Drug Information|url=https://books.google.com/books?id=WR0NAQAAMAAJ|year=1990|publisher=Published by authority of the Board of Directors of the American Society of Hospital Pharmacists|access-date=9 October 2017|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114195325/https://books.google.com/books?id=WR0NAQAAMAAJ|url-status=live}}</ref> Tinjauan farmakokinetik antihistamin tahun 1985 menemukan bahwa waktu paruh eliminasi difenhidramin berkisar antara 3,4 dan 9,3 jam dalam lima penelitian, dengan waktu paruh eliminasi rata-rata 4,3 jam.<ref name="pmid2866055"/> Sebuah studi berikutnya pada tahun 1990 menemukan bahwa waktu paruh eliminasi difenhidramin adalah 5,4 jam pada anak-anak; 9,2 jam pada orang dewasa muda; dan 13,5 jam pada orang tua.<ref name="pmid2391399">{{cite journal | vauthors = Simons KJ, Watson WT, Martin TJ, Chen XY, Simons FE | title = Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults, and children | url = https://archive.org/details/sim_journal-of-clinical-pharmacology_1990-07_30_7/page/665 | journal = Journal of Clinical Pharmacology | volume = 30 | issue = 7 | pages = 665–71 | date = July 1990 | pmid = 2391399 | doi = 10.1002/j.1552-4604.1990.tb01871.x | s2cid = 25452263 }}</ref> Sebuah penelitian tahun 1998 menemukan waktu paruh 4,1 ± 0,3 jam pada pria muda; 7,4 ± 3,0 jam pada pria lanjut usia; 4,4 ± 0,3 jam pada wanita muda; dan 4,9 ± 0,6 jam pada wanita lanjut usia.<ref name="pmid9702844">{{cite journal | vauthors = Scavone JM, Greenblatt DJ, Harmatz JS, Engelhardt N, Shader RI | title = Pharmacokinetics and pharmacodynamics of diphenhydramine 25 mg in young and elderly volunteers | journal = J Clin Pharmacol | volume = 38 | issue = 7 | pages = 603–9 | date = July 1998 | pmid = 9702844 | doi = 10.1002/j.1552-4604.1998.tb04466.x | s2cid = 24989721 | url =https://archive.org/details/sim_journal-of-clinical-pharmacology_1998-07_38_7/page/603}}</ref> Dalam sebuah penelitian tahun 2018 pada anak-anak dan remaja, waktu paruh difenhidramin adalah 8 hingga 9 jam.<ref name="pmid28967696">{{cite journal | vauthors = Gelotte CK, Zimmerman BA, Thompson GA | title = Single-Dose Pharmacokinetic Study of Diphenhydramine HCl in Children and Adolescents | journal = Clin Pharmacol Drug Dev | volume = 7 | issue = 4 | pages = 400–407 | date = May 2018 | pmid = 28967696 | pmc = 5947143 | doi = 10.1002/cpdd.391 | url = }}</ref>
==Kimia==
Difenhidramin adalah turunan difenilmetana. Analogi difenhidramin termasuk orfenadrin, suatu [[antikolinergik]]; nefopam, suatu [[analgesik]]; dan tofenasin, suatu [[antidepresan]].
Baris 134 ⟶ 246:
==Dalam Budaya Masyarakat==
Difenhidramin dianggap memiliki potensi penyalahgunaan yang terbatas di Amerika Serikat karena profil efek sampingnya yang serius dan efek euforia yang terbatas, dan bukan merupakan zat yang dikendalikan. Sejak tahun 2002, [[Badan Pengawas Obat dan Makanan Amerika Serikat]] telah mewajibkan peringatan pelabelan khusus terhadap penggunaan beberapa produk yang mengandung difenhidramin.<ref>{{cite journal | author = Food and Drug Administration, HHS | title = Labeling of diphenhydramine-containing drug products for over-the-counter human use. Final rule | journal = Federal Register | volume = 67 | issue = 235 | pages = 72555–9 | date = December 2002 | pmid = 12474879 | url = https://www.fda.gov/OHRMS/DOCKETS/98fr/120602a.htm | archive-url = https://web.archive.org/web/20081105004602/https://www.fda.gov/OHRMS/DOCKETS/98fr/120602a.htm | df = dmy-all | url-status = live | archive-date = 5 November 2008 }}</ref> Di beberapa [[yurisdiksi]], difenhidramin sering terdapat dalam spesimen ''postmortem'' yang dikumpulkan selama penyelidikan kematian bayi mendadak; obat tersebut mungkin berperan dalam kejadian ini.<ref name="pmid16419411">{{cite journal | vauthors = Marinetti L, Lehman L, Casto B, Harshbarger K, Kubiczek P, Davis J | title = Over-the-counter cold medications-postmortem findings in infants and the relationship to cause of death | journal = Journal of Analytical Toxicology | volume = 29 | issue = 7 | pages = 738–43 | date = October 2005 | pmid = 16419411 | doi = 10.1093/jat/29.7.738 | doi-access = free }}</ref><ref name="isbn0-9626523-7-7">{{cite book | vauthors = Baselt RC | title = Disposition of Toxic Drugs and Chemicals in Man | url = https://archive.org/details/dispositionoftox0000base_v7n5 | publisher = Biomedical Publications | year = 2008 | pages = [https://archive.org/details/dispositionoftox0000base_v7n5/page/489 489]–492 | isbn = 978-0-9626523-7-0 }}</ref>
Difenhidramin merupakan salah satu zat yang dilarang dan dikontrol di Republik [[Zambia]],<ref>{{cite web | url = http://www.gctrips.org/documents/IllegaldrugsinZambia.docx <!-- original "http://www.deczambia.gov.zm/listofdrugs.html link" is dead --> | format = DOC | title = List of prohibited and controlled drugs according to chapter 96 of the laws of Zambia | publisher = The Drug Enforcement Commission ZAMBIA | url-status = dead | archive-url = https://web.archive.org/web/20131116010729/http://www.gctrips.org/documents/IllegaldrugsinZambia.docx | archive-date = 16 November 2013 | df = dmy-all | access-date = 20 March 2013 }}</ref> dan wisatawan disarankan untuk tidak membawa obat tersebut ke negara tersebut. Beberapa orang Amerika telah ditahan oleh Komisi Penegakan Narkoba Zambia karena memiliki [[Benadryl]] dan obat-obatan lain yang dijual bebas yang mengandung difenhidramin.<ref>{{cite web | url = https://travel.state.gov/content/passports/english/country/zambia.html | title = Zambia | work = Country Information > Zambia | publisher = Bureau of Consular Affairs, U.S. Department of State | access-date = 17 July 2015 | url-status = live | archive-url = https://web.archive.org/web/20150721232323/http://travel.state.gov/content/passports/english/country/zambia.html | archive-date = 21 July 2015 | df = dmy-all }}</ref>
===Penggunaan rekreasi===
Meskipun difenhidramin banyak digunakan dan umumnya dianggap aman untuk penggunaan sesekali, banyak kasus [[penyalahgunaan obat]] dan [[kecanduan]] telah didokumentasikan.<ref name="Thomas2008">{{cite journal | vauthors = Thomas A, Nallur DG, Jones N, Deslandes PN | title = Diphenhydramine abuse and detoxification: a brief review and case report | journal = Journal of Psychopharmacology | volume = 23 | issue = 1 | pages = 101–5 | date = January 2009 | pmid = 18308811 | doi = 10.1177/0269881107083809 | s2cid = 45490366 }}</ref> Karena obat ini murah dan dijual bebas di sebagian besar negara, remaja yang tidak memiliki akses terhadap obat-obatan terlarang, sangat berisiko.<ref name="urlAtypical Drugs of Abuse">{{cite web | url = http://studentdoctor.net/2008/07/atypical-drugs-of-abuse/ | title = Atypical Drugs of Abuse | vauthors = Forest E | date = 27 July 2008 | work = Articles & Interviews | publisher = Student Doctor Network | url-status = live | archive-url = https://web.archive.org/web/20130527231559/http://studentdoctor.net/2008/07/atypical-drugs-of-abuse/ | archive-date = 27 May 2013 | df = dmy-all }}</ref> Orang dengan masalah kesehatan mental—terutama penderita [[skizofrenia]]—juga rentan menyalahgunakan obat tersebut, yang diberikan sendiri dalam dosis besar untuk mengobati gejala ekstrapiramidal yang disebabkan oleh penggunaan [[antipsikotik]].<ref name="Halpert2002">{{cite journal | vauthors = Halpert AG, Olmstead MC, Beninger RJ | title = Mechanisms and abuse liability of the anti-histamine dimenhydrinate | journal = Neuroscience and Biobehavioral Reviews | volume = 26 | issue = 1 | pages = 61–7 | date = January 2002 | pmid = 11835984 | doi = 10.1016/s0149-7634(01)00038-0 | s2cid = 46619422 | url = http://www.queensu.ca/psychology/sites/webpublish.queensu.ca.psycwww/files/files/Faculty/Richard%20Beninger/Beninger_prp_25.pdf | access-date = 23 December 2017 | archive-date = 2 August 2020 | archive-url = https://web.archive.org/web/20200802230007/https://www.queensu.ca/psychology/sites/webpublish.queensu.ca.psycwww/files/files/Faculty/Richard%20Beninger/Beninger_prp_25.pdf | url-status = dead }}</ref>
Pengguna rekreasional melaporkan efek menenangkan, euforia ringan, dan halusinasi sebagai efek yang diinginkan dari obat tersebut.<ref name="Halpert2002"/><ref>{{cite journal | vauthors = Gracious B, Abe N, Sundberg J | title = The importance of taking a history of over-the-counter medication use: a brief review and case illustration of "PRN" antihistamine dependence in a hospitalized adolescent | journal = Journal of Child and Adolescent Psychopharmacology | volume = 20 | issue = 6 | pages = 521–4 | date = December 2010 | pmid = 21186972 | pmc = 3025184 | doi = 10.1089/cap.2010.0031 }}</ref> Penelitian telah menunjukkan bahwa agen antimuskarinik, termasuk difenhidramin, "mungkin memiliki sifat antidepresan dan meningkatkan suasana hati".<ref>{{cite journal | vauthors = Dilsaver SC | title = Antimuscarinic agents as substances of abuse: a review | journal = Journal of Clinical Psychopharmacology | volume = 8 | issue = 1 | pages = 14–22 | date = February 1988 | pmid = 3280616 | doi = 10.1097/00004714-198802000-00003 | s2cid = 31355546 }}</ref> Sebuah penelitian yang dilakukan pada pria dewasa dengan riwayat penyalahgunaan obat penenang menemukan bahwa subjek yang diberikan difenhidramin dosis tinggi (400 mg) melaporkan keinginan untuk menggunakan obat tersebut lagi, meskipun juga melaporkan efek negatif seperti kesulitan berkonsentrasi, kebingungan, [[tremor]], dan penglihatan kabur.<ref>{{cite journal | vauthors = Mumford GK, Silverman K, Griffiths RR |title=Reinforcing, subjective, and performance effects of lorazepam and diphenhydramine in humans |journal=[[Experimental and Clinical Psychopharmacology]] |date=1996 |volume=4 |issue=4 |pages=421–430 |doi=10.1037/1064-1297.4.4.421}}</ref>
Pada tahun 2020, tantangan internet muncul di platform media sosial [[TikTok]] yang melibatkan overdosis difenhidramin secara sengaja; dijuluki tantangan Benadryl, tantangan ini mendorong peserta untuk mengonsumsi Benadryl dalam jumlah yang berbahaya dengan tujuan merekam efek psikoaktif yang dihasilkan, dan telah menyebabkan beberapa rawat inap<ref>{{Cite web|title=TikTok Videos Encourage Viewers to Overdose on Benadryl|url=https://www.checkupnewsroom.com/tiktok-videos-encourage-viewers-to-overdose-on-benadryl/|access-date=9 October 2020|website=TikTok Videos Encourage Viewers to Overdose on Benadryl|archive-date=8 October 2020|archive-url=https://web.archive.org/web/20201008114600/https://www.checkupnewsroom.com/tiktok-videos-encourage-viewers-to-overdose-on-benadryl/|url-status=live}}</ref> dan setidaknya dua kematian.<ref>{{Cite web|date=28 August 2020|title=Dangerous 'Benadryl Challenge' on Tik Tok may be to blame for the death of Oklahoma teen|url=https://kfor.com/news/local/dangerous-benadryl-challenge-on-tik-tok-blamed-for-the-death-of-oklahoma-teen/|access-date=9 October 2020|website=KFOR.com Oklahoma City|archive-date=2 August 2021|archive-url=https://web.archive.org/web/20210802073032/https://kfor.com/news/local/dangerous-benadryl-challenge-on-tik-tok-blamed-for-the-death-of-oklahoma-teen/|url-status=live}}</ref><ref>{{Cite web|date=25 September 2020|title=Teen's Death Prompts Warning on 'Benadryl Challenge'|url=https://www.medpagetoday.com/pediatrics/generalpediatrics/88816|access-date=9 October 2020|website=www.medpagetoday.com|archive-date=29 September 2020|archive-url=https://web.archive.org/web/20200929121653/https://www.medpagetoday.com/pediatrics/generalpediatrics/88816|url-status=live}}</ref><ref>{{Cite web |date=2023-04-23 |title=What is the Benadryl challenge? New TikTok challenge that's left 13-year-old dead |url=https://www.independent.co.uk/news/long_reads/world/tiktok-benadryl-challenge-death-13-year-old-b2325133.html |access-date=2023-04-23 |website=The Independent }}</ref>
==Referensi==
{{Reflist}}
[[Kategori:
[[Kategori:Antihistamin]]
[[Kategori:Antikolinergik]]
[[Kategori:Halusinogen]]
[[Kategori:Delirian]]
[[Kategori:Sedatif]]
[[Kategori:
[[Kategori:Anksiolitik]]
[[Kategori:Penghambat CYP2D6]]
[[Kategori:Senyawa dimetilamino]]
[[Kategori:Eter difenilmetanol]]
[[Kategori:Penghambat enzim]]
[[Kategori:Antagonis reseptor H1]]
[[Kategori:Anestesi lokal]]
[[Kategori:Antagonis muskarinik]]
[[Kategori:Oneirogen]]
[[Kategori:Penghambat pengambilan kembali serotonin]]
[[Kategori:Amina tersier]]
==Bacaan Lebih Lanjut==
{{Refbegin}}
* {{cite journal | vauthors = Björnsdóttir I, Einarson TR, Gudmundsson LS, Einarsdóttir RA | title = Efficacy of diphenhydramine against cough in humans: a review | journal = Pharmacy World & Science | volume = 29 | issue = 6 | pages = 577–83 | date = December 2007 | pmid = 17486423 | doi = 10.1007/s11096-007-9122-2 | s2cid = 8168920 }}
* {{cite journal | vauthors = Cox D, Ahmed Z, McBride AJ | title = Diphenhydramine dependence | url = https://archive.org/details/sim_british-journal-of-addiction_2001-03_96_3/page/516 | journal = Addiction | volume = 96 | issue = 3 | pages = 516–7 | date = March 2001 | pmid = 11310441 }}
* {{cite journal | vauthors = Lieberman JA | title = History of the use of antidepressants in primary care | journal = Primary Care Companion J. Clinical Psychiatry | volume = 5 | issue = supplement 7 | pages = 6–10 | year = 2003 | url = http://www.psychiatrist.com/pcc/pccpdf/v05s07/v05s0702.pdf | access-date = 19 March 2013 | archive-date = 11 June 2014 | archive-url = https://web.archive.org/web/20140611094425/http://www.psychiatrist.com/pcc/pccpdf/v05s07/v05s0702.pdf | url-status = dead }}
{{Refend}}
== Pranala
{{Commons category-inline|Difenhidramin}}
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