Editing Hydrocodone (section)

{{Short description|Opioid drug used in pain relief}}
{{Distinguish|Dihydrocodeine}}
{{Use dmy dates|date=June 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 443251358
| image = Hydrocodone skeletal.svg
| image_class = skin-invert-image
| width = 200
| alt = 
| image2 = Hydrocodone-Spartan-PM3-3D-balls.png
| width2 = 225
| alt2 = 

<!-- Clinical data -->
| pronounce = 
| tradename = Hysingla ER, Zohydro ER
| Drugs.com = {{drugs.com|monograph|hydrocodone-bitartrate}}
| MedlinePlus = a601006
| DailyMedID = Hydrocodone
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment = 
| pregnancy_category = 
| dependency_liability = High<ref>{{cite book |vauthors=Bonewit-West K, Hunt SA, Applegate E |title=Today's Medical Assistant: Clinical and Administrative Procedures |date=2012 |page=571 |publisher=Elsevier Health Sciences |isbn=9781455701506 |url=https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 |access-date=20 August 2019 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110030031/https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 |url-status=live }}</ref>
| addiction_liability = High
| class = [[Opioid]]
| routes_of_administration = Clinical: [[oral administration|By mouth]]<ref name="ElliottSmith2016" /><br />Others: [[intranasal administration|Intranasal]], [[rectal administration|rectal]]
| ATC_prefix = R05
| ATC_suffix = DA03
| ATC_supplemental = 

<!-- Legal status -->
| legal_AU = Schedule 8
| legal_AU_comment = 
| legal_BR = A1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = Schedule I
| legal_CA_comment = 
| legal_DE = Anlage III
| legal_DE_comment = 
| legal_NZ = Class B
| legal_NZ_comment = 
| legal_UK = Class A
| legal_UK_comment = 
| legal_US = Schedule II
| legal_US_comment = 
| legal_EU = 
| legal_EU_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = SE: Förteckning II

<!-- Pharmacokinetic data -->
| bioavailability = Oral: 70%<ref name="FiresteinBudd2016">{{cite book|vauthors=Polsten GR, Wallace MS|chapter=Analgesic Agents in Rheumatic Disease|veditors=Firestein GS, Budd R, Gabriel SE, McInnes IB, O'Dell JR|title=Kelley and Firestein's Textbook of Rheumatology|chapter-url=https://books.google.com/books?id=kBZ6DAAAQBAJ&pg=PA1081|date=21 June 2016|publisher=Elsevier Health Sciences|isbn=978-0-323-41494-4|pages=1081–|access-date=23 September 2016|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112203342/https://www.google.com/books/edition/Kelley_and_Firestein_s_Textbook_of_Rheum/kBZ6DAAAQBAJ?hl=en&gbpv=1&pg=PA1081&printsec=frontcover|url-status=live}}</ref>
| protein_bound = Low<ref name="FiresteinBudd2016" /><ref name="ChabnerLongo2010">{{cite book|chapter=Chapter 37: Drug Therapy of Pain in Cancer Patients|vauthors=Chabner BA, Longo DL|title=Cancer Chemotherapy and Biotherapy: Principles and Practice|chapter-url=https://books.google.com/books?id=WL4arNFsQa8C&pg=PA700|date=8 November 2010|publisher=Lippincott Williams & Wilkins|isbn=978-1-60547-431-1|pages=700–|access-date=23 September 2016|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112203349/https://books.google.com/books?id=WL4arNFsQa8C&pg=PA700|url-status=live}}</ref>
| metabolism = [[Liver]]: [[CYP3A4]] (major), [[CYP2D6]] (minor)<ref name="Zhou2016" />
| metabolites = [[Norhydrocodone]]<ref name="Zhou2016" /><br /> [[Hydromorphone]]<ref name="Zhou2016" /><br /> Others<ref name="Zhou2016" />
| onset = 10–20 minutes<ref name="ElliottSmith2016" />
| elimination_half-life = Average: 3.8 hours<ref name="DavisGlare2005" /><br />Range: 3.3–4.4 hours<ref name="ElliottSmith2016" />
| duration_of_action = 4–8 hours<ref name="ElliottSmith2016" />
| excretion = [[Urine]]<ref name="Bluth2016">{{cite book|vauthors=Bluth MH|title=Toxicology and Drug Testing, An Issue of Clinics in Laboratory Medicine, E-Book|url=https://books.google.com/books?id=NAKRDQAAQBAJ&pg=PT85|date=16 November 2016|publisher=Elsevier Health Sciences|isbn=978-0-323-47795-6|pages=85–|access-date=22 June 2018|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112203353/https://books.google.com/books?id=NAKRDQAAQBAJ&pg=PT85|url-status=live}}</ref><ref name="Smith2013">{{cite book|vauthors=Smith HS|title=Opioid Therapy in the 21st Century|url=https://books.google.com/books?id=MBxWFigSEE8C&pg=PT68|date=21 February 2013|publisher=OUP USA|isbn=978-0-19-984497-5|pages=68–|access-date=22 June 2018|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112203347/https://books.google.com/books?id=MBxWFigSEE8C&pg=PT68|url-status=live}}</ref>

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 125-29-1
| PubChem = 5284569
| IUPHAR_ligand = 7081
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00956
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4447623
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6YKS4Y3WQ7
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08045
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 5779
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1457
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = Dihydrocodeinone, hydrocodone bitartrate

<!-- Chemical and physical data -->
| IUPAC_name = 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one
| C = 18
| H = 21
| N = 1
| O = 3
| SMILES = O=C4[C@@H]5Oc1c2c(ccc1OC)C[C@H]3N(CC[C@]25[C@H]3CC4)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3,6,11-12,17H,4-5,7-9H2,1-2H3/t11-,12+,17-,18-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = LLPOLZWFYMWNKH-CMKMFDCUSA-N
| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

'''Hydrocodone''', also known as '''dihydrocodeinone''', is a semi-synthetic [[opioid]] used to treat [[pain]] and as a [[Cold medicine|cough suppressant]].<ref name="AHFS2019">{{cite web|title=Hydrocodone Bitartrate Monograph for Professionals|url=https://www.drugs.com/monograph/hydrocodone-bitartrate.html|access-date=15 April 2019|website=Drugs.com|publisher=American Society of Health-System Pharmacists|archive-date=14 November 2010|archive-url=https://web.archive.org/web/20101114074840/https://www.drugs.com/monograph/hydrocodone-bitartrate.html|url-status=live}}</ref> It is taken by mouth.<ref name="AHFS2019" /> Typically, it is dispensed as the combination [[Hydrocodone/paracetamol|acetaminophen/hydrocodone]] or [[Hydrocodone/ibuprofen|ibuprofen/hydrocodone]] for pain severe enough to require an opioid<ref>{{Cite web|last=Mallinckrodt|date=10 March 2021|title=HYDROCODONE BITARTRATE AND ACETAMINOPHEN tablet (label)|url=https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=73c1059b-0c7d-42ef-9827-f018858fc447|access-date=6 November 2021|website=National Institutes of Health DailyMed|archive-date=6 November 2021|archive-url=https://web.archive.org/web/20211106121028/https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=73c1059b-0c7d-42ef-9827-f018858fc447|url-status=live}}</ref><ref name="Bri2011">{{cite book| vauthors = Briggs GG, Freeman RK, Yaffe SJ |url=https://books.google.com/books?id=OIgTE4aynrMC&pg=PA692|title=Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk|date=2011|publisher=Lippincott Williams & Wilkins|isbn=9781608317080|page=692}}</ref><ref>{{Cite web |title=Hydrocodone Combination Products: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a601006.html |access-date=4 November 2023 |website=medlineplus.gov |language=en |archive-date=5 July 2016 |archive-url=https://web.archive.org/web/20160705111552/https://www.nlm.nih.gov/medlineplus/druginfo/meds/a601006.html |url-status=live }}</ref> and in combination with [[homatropine methylbromide]] to relieve cough.<ref name="AHFS2019" /> It is also available by itself in a long-acting form sold under the brand name '''Zohydro ER''', among others, to treat severe pain of a prolonged duration.<ref name="AHFS2019" /><ref name="Med2019">{{cite web|title=Hydrocodone: MedlinePlus Drug Information|url=https://medlineplus.gov/druginfo/meds/a614045.html|access-date=15 April 2019|website=medlineplus.gov|archive-date=15 April 2019|archive-url=https://web.archive.org/web/20190415183043/https://medlineplus.gov/druginfo/meds/a614045.html|url-status=live}}</ref> Hydrocodone is a controlled drug: in the United States, it is classified as a [[Schedule II Controlled Substance|Schedule II]] [[Controlled substance|Controlled Substance]].

<!-- Side effects and mechanisms -->
Common side effects include [[dizziness]], [[sleepiness]], [[nausea]], and [[constipation]].<ref name="AHFS2019" /> Serious side effects may include [[low blood pressure]], [[seizures]], [[QT prolongation]], [[respiratory depression]], and [[serotonin syndrome]].<ref name=AHFS2019/> Rapidly decreasing the dose may result in [[opioid withdrawal]].<ref name=AHFS2019/> Use during [[pregnancy]] or [[breastfeeding]] is generally not recommended.<ref name=Preg2019>{{cite web |title=Hydrocodone Use During Pregnancy |url=https://www.drugs.com/pregnancy/hydrocodone.html |website=Drugs.com |access-date=15 April 2019 |archive-date=28 January 2014 |archive-url=https://web.archive.org/web/20140128132937/https://www.drugs.com/pregnancy/hydrocodone.html |url-status=live }}</ref> Hydrocodone is believed to work by activating [[opioid receptor]]s, mainly in the brain and spinal cord.<ref name=AHFS2019/> Hydrocodone 10&nbsp;mg is equivalent to about 10&nbsp;mg of [[morphine]] by mouth.<ref>{{cite web |title=Opioid Dose Calculator |url=http://www.agencymeddirectors.wa.gov/calculator/dosecalculator.htm |website=Agency Medical Directors' Group |access-date=15 April 2019 |archive-date=10 February 2016 |archive-url=https://web.archive.org/web/20160210070737/http://www.agencymeddirectors.wa.gov/calculator/dosecalculator.htm |url-status=dead }}</ref>

<!-- History and culture -->
Hydrocodone was patented in 1923, while the long-acting formulation was approved for medical use in the United States in 2013.<ref name=AHFS2019/><ref name=Fis2006 /> It is most commonly prescribed in the United States, which consumed 99% of the worldwide supply as of 2010.<ref>{{cite news |title=Making Some Painkillers Harder to Get |url=https://www.nytimes.com/2013/02/22/opinion/making-some-painkillers-harder-to-get.html |archive-url=https://ghostarchive.org/archive/20220103/https://www.nytimes.com/2013/02/22/opinion/making-some-painkillers-harder-to-get.html |archive-date=3 January 2022 |url-access=subscription |url-status=live |access-date=15 April 2019 |work=The New York Times |date=21 February 2013}}{{cbignore}}</ref> In 2018, it was the 402nd most commonly prescribed medication in the United States, with more than 400,000 prescriptions.<ref name="Hydrocodone - Drug Usage Statistics">{{cite web | title = Hydrocodone - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Hydrocodone | access-date = 7 October 2022 | archive-date = 13 November 2022 | archive-url = https://web.archive.org/web/20221113222415/https://clincalc.com/DrugStats/Drugs/Hydrocodone | url-status = live }}</ref> Hydrocodone is a semisynthetic opioid, converted from [[codeine]]<ref>{{cite book| vauthors = Stoker HS |url=https://books.google.com/books?id=lPltCgAAQBAJ&pg=PA567|title=General, Organic, and Biological Chemistry|date=2012|publisher=Cengage Learning|isbn=9781133711285|page=567}}</ref><ref>{{Cite book| vauthors = Vardanyan R, Hruby V |url=https://books.google.com/books?id=Jjc7KYWZdOYC&q=hydrocodone|title=Synthesis of Essential Drugs|date=10 March 2006|publisher=Elsevier|isbn=978-0-08-046212-7|language=en}}</ref> or less often from [[thebaine]].<ref>{{Cite book|url=https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2020/Narcotic_Drugs_Technical_publication_2020.pdf|title=Narcotic Drugs 2020, Estimated World Requirements for 2021, Statistics for 2019|publisher=International Narcotics Control Board|year=2020|isbn=978-92-1-148355-0|pages=37|quote=Thebaine itself is not used in therapy, but it is an important starting material for the manufacture of a number of opioids, mainly codeine, dihydrocodeine, etorphine, hydrocodone, oxycodone and oxymorphone...|access-date=12 December 2021|archive-date=3 November 2021|archive-url=https://web.archive.org/web/20211103162923/https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2020/Narcotic_Drugs_Technical_publication_2020.pdf|url-status=live}}</ref> Production using genetically engineered yeasts has been developed but is not used commercially.<ref>{{cite journal | vauthors = Galanie S, Thodey K, Trenchard IJ, Filsinger Interrante M, Smolke CD | title = Complete biosynthesis of opioids in yeast | journal = Science | volume = 349 | issue = 6252 | pages = 1095–1100 | date = September 2015 | pmid = 26272907 | pmc = 4924617 | doi = 10.1126/science.aac9373 | bibcode = 2015Sci...349.1095G }}</ref><ref>{{cite journal | vauthors = Thodey K, Galanie S, Smolke CD | title = A microbial biomanufacturing platform for natural and semisynthetic opioids | journal = Nature Chemical Biology | volume = 10 | issue = 10 | pages = 837–844 | date = October 2014 | pmid = 25151135 | pmc = 4167936 | doi = 10.1038/nchembio.1613 }}</ref><ref>{{cite journal | vauthors = Nakagawa A, Matsumura E, Koyanagi T, Katayama T, Kawano N, Yoshimatsu K, Yamamoto K, Kumagai H, Sato F, Minami H | title = Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli | journal = Nature Communications | volume = 7 | issue = 1 | pages = 10390 | date = February 2016 | pmid = 26847395 | pmc = 4748248 | doi = 10.1038/ncomms10390 | bibcode = 2016NatCo...710390N }}</ref>

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