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Difenhidramin: Perbedaan antara revisi

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(7 revisi perantara oleh 4 pengguna tidak ditampilkan)
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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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[[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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===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===
DiphenhydramineDifenhidramin juga memiliki sifat [[Antimuntah|antiemetik]] sehingga berguna dalam mengobati mual yang terjadi pada [[vertigo]] dan mabuk perjalanan. Namun, bila dikonsumsi melebihi dosis yang dianjurkan, dapat menyebabkan mual (terutama di atas 200 mg).<ref>{{cite journal |vauthors = Flake ZA, Scalley RD, Bailey AG |title = Practical selection of antiemetics |journal = American Family Physician |volume = 69 |issue = 5 |pages = 1169–74 |date = March 2004 |pmid = 15023018 |url = http://www.aafp.org/afp/2004/0301/p1169.html |access-date = 10 March 2016 |df = dmy-all |url-status = live |archive-url = https://web.archive.org/web/20160324141234/http://www.aafp.org/afp/2004/0301/p1169.html |archive-date = 24 March 2016}}</ref>
 
===Populasi Khusus===
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| [[Reseptor asetilkolin muskarinik M2|M<sub>2</sub>]] || 120–490 || Manusia || <ref name="pmid1346637" /><ref name="pmid23357028" />
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| [[Reseptor asetilkolin muskarinik M3|M<sub>3</sub>]] || 84–229 || HumanManusia || <ref name="pmid1346637" /><ref name="pmid23357028" />
|-
| [[Reseptor asetilkolin muskarinik M4|M<sub>4</sub>]] || 53–112 || Manusia || <ref name="pmid1346637" /><ref name="pmid23357028" />
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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 = 242–245[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.
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===Farmakokinetik===
[[Bioavailabilitas]] oral diphenhydraminedifenhidramin 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 dioksidasidi[[Redoks|oksidasi]] menjadi [[asam karboksilat]].<ref name="pmid2866055"/> DiphenhydramineDifenhidramin 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 diphenhydraminedifenhidramin 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 diphenhydraminedifenhidramin 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 diphenhydraminedifenhidramin 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 diphenhydraminedifenhidramin 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==
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==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 = 489–492[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>
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==Referensi==
{{Reflist}}
[[Kategori:ObatAntagonis 5-HT2C]]
[[Kategori:Antihistamin]]
[[Kategori:Antikolinergik]]
[[Kategori:Etanolamin]]▼
[[Kategori:Halusinogen]]
[[Kategori:Delirian]]
[[Kategori:Sedatif]]
[[Kategori:AntimuntahAntiemetik]]
[[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:EtanolaminOneirogen]]
[[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 Luarluar ==
{{Commons category-inline|Difenhidramin}}
Diperoleh dari "https://wiki-indonesia.club/wiki/Difenhidramin"