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Revision as of 14:58, 24 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456783665 of page Oxybutynin for the Chem/Drugbox validation project (updated: 'DrugBank').  Latest revision as of 05:41, 13 November 2024 edit Slothwizard (talk | contribs)Extended confirmed users1,190 editsmNo edit summaryTags: Visual edit Mobile edit Mobile web edit 
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{{Short description|Medication for overactive bladder}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{Use mdy dates|date=June 2024}}
{{Drugbox
{{cs1 config|name-list-style=vanc|display-authors=6}}
| Verifiedfields = changed
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 411820278 | verifiedrevid = 462267372
| image = Oxybutynin.svg
| IUPAC_name = 4-Diethylaminobut-2-ynyl 2-cyclohexyl-2-hydroxy-2-phenylethanoate
| alt =
| image = Oxybutynin structure.png
| image2 = Oxybutynin 3d balls.png | image2 = Oxybutynin 3d balls.png
| alt2 = <!-- Clinical data -->

| pronounce =
<!--Clinical data-->
| tradename = Ditropan | tradename = Ditropan, Gelnique, others
| Drugs.com = {{drugs.com|monograph|oxybutynin-chloride}} | Drugs.com = {{drugs.com|monograph|oxybutynin-chloride}}
| MedlinePlus = a682141 | MedlinePlus = a682141
| DailyMedID = Oxybutynin
| pregnancy_category = B
| pregnancy_AU = B1
| legal_status = Rx Only (CA)<ref>{{cite web | url = http://webprod3.hc-sc.gc.ca/dpd-bdpp/info.do?lang = eng&code = 67903 | title = Product Information | publisher = ] | accessdate = 2011-08-13}}</ref>, Rx Only (US)
| pregnancy_AU_comment =
| routes_of_administration = oral, transdermal
| pregnancy_category =

| routes_of_administration = ], ]
<!--Pharmacokinetic data-->
| class = ]
| bioavailability =
| ATC_prefix = G04
| protein_bound = 91%-93%
| metabolism = | ATC_suffix = BD04
| ATC_supplemental = <!-- Legal status -->
| elimination_half-life = 12.4-13.2 hours
| legal_AU = S4
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment = /{{nbsp}}OTC<ref>{{cite web | title=Ditropan XL (oxybutynin chloride) Extended Release Tablets for oral use Initial U.S. Approval: 1975 | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=693342 | access-date=June 17, 2024}}</ref><ref>{{cite web | title=Gelnique- oxybutynin chloride gel | website=DailyMed | date=March 1, 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57616d79-9e68-4ec7-a25f-ebee07576351 | access-date=June 17, 2024}}</ref><ref>{{cite web | title=Oxytrol- oxybutynin patch | website=DailyMed | date=May 29, 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=20dee37f-1412-44ed-9e8b-f4379ce23eb0 | access-date=June 17, 2024}}</ref><ref>{{cite web | title=Oxytrol for Women- oxybutynin patch | website=DailyMed | date=August 13, 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8cdc5b4d-ff8d-4010-97d7-313422a0b868 | access-date=June 17, 2024}}</ref>
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web | title=Kentera EPAR | website=European Medicines Agency (EMA) | date=15 June 2004 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/kentera | access-date=12 October 2024}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->


<!-- Pharmacokinetic data -->| bioavailability =
<!--Identifiers-->
| protein_bound = 91–93%
| CASNo_Ref = {{cascite|correct|CAS}}
| metabolism =
| metabolites = ''N''-Desethyloxybutynin
| onset =
| elimination_half-life = 12.4–13.2 hours
| duration_of_action =
| excretion = <!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 5633-20-5 | CAS_number = 5633-20-5
| ATC_prefix = G04 | CAS_supplemental =
| ATC_suffix = BD04
| ATC_supplemental =
| PubChem = 4634 | PubChem = 4634
| IUPHAR_ligand = 359 | IUPHAR_ligand = 359
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| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00465 | KEGG = D00465
| ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 7856 | ChEBI = 7856
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1231 | ChEMBL = 1231
| NIAID_ChemDB =

| PDB_ligand =
<!--Chemical data-->
| synonyms = <!-- Chemical and physical data -->
| C=22 | H=31 | N=1 | O=3
| IUPAC_name = 4-Diethylaminobut-2-ynyl 2-cyclohexyl-2-hydroxy-2-phenylethanoate
| molecular_weight = 357.486 g/mol
| C = 22
| smiles = O=C(OCC#CCN(CC)CC)C(O)(c1ccccc1)C2CCCCC2
| H = 31
| InChI = 1/C22H31NO3/c1-3-23(4-2)17-11-12-18-26-21(24)22(25,19-13-7-5-8-14-19)20-15-9-6-10-16-20/h5,7-8,13-14,20,25H,3-4,6,9-10,15-18H2,1-2H3
| N = 1
| InChIKey = XIQVNETUBQGFHX-UHFFFAOYAB
| O = 3
| SMILES = O=C(OCC#CCN(CC)CC)C(O)(c1ccccc1)C2CCCCC2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C22H31NO3/c1-3-23(4-2)17-11-12-18-26-21(24)22(25,19-13-7-5-8-14-19)20-15-9-6-10-16-20/h5,7-8,13-14,20,25H,3-4,6,9-10,15-18H2,1-2H3 | StdInChI = 1S/C22H31NO3/c1-3-23(4-2)17-11-12-18-26-21(24)22(25,19-13-7-5-8-14-19)20-15-9-6-10-16-20/h5,7-8,13-14,20,25H,3-4,6,9-10,15-18H2,1-2H3
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XIQVNETUBQGFHX-UHFFFAOYSA-N | StdInChIKey = XIQVNETUBQGFHX-UHFFFAOYSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}} }}

<!-- Definition and medical uses -->
'''Oxybutynin''', sold under the brand name '''Ditropan''' among others, is an ] medication primarily used to treat ]. It is widely considered a ] for overactive bladder due to its well-studied side effect profile, broad applicability, and continued efficacy over long periods of time. It works similar to ], ], and ], although it is usually preferred over these medications. It is sometimes used ] for treatment of ], or excessive sweating. It has also been used off-label to treat ] in children, but this use has declined, as it is most likely ineffective in this role. It is taken ] or ].

<!-- Side effects and mechanisms -->
Common side effects include ], ], ], ], and ].<ref name=AHFS2019/> Serious side effects may include ] and an increased risk of ].<ref name=AHFS2019/> Use in ] appears safe but has not been well studied while use in ] is of unclear safety.<ref name=Preg2019>{{cite web |title=Oxybutynin Pregnancy and Breastfeeding Warnings |url=https://www.drugs.com/pregnancy/oxybutynin.html |website=Drugs.com |access-date=March 3, 2019 }}</ref> It is an ] and works by blocking the effects of ] on ].<ref name=AHFS2019>{{cite web |title=Oxybutynin Chloride Monograph for Professionals |url=https://www.drugs.com/monograph/oxybutynin-chloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=March 3, 2019 }}</ref>

<!-- History and culture -->
Oxybutynin was approved for medical use in the US in 1975.<ref name=AHFS2019/> It is available as a ].<ref name=BNF76>{{cite book|title=British National Formulary: BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=978-0-85711-338-2|edition=76th}}</ref> In 2022, it was the 110th most commonly prescribed medication in the United States, with more than 5{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Oxybutynin Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Oxybutynin | access-date = 30 August 2024 }}</ref>

==Medical use==
Oxybutynin is used in the form of instant-release capsules, ] capsules, or transdermal (]) products. All of these are considered safe and effective options for treatment of ]-mediated ].<ref name=AHFS2019/> Extended-release formulations decrease the number of weekly incontinence episodes by an average of 90% compared to an untreated state.<ref name=":0">{{cite journal | vauthors = Diokno A, Ingber M | title = Oxybutynin in detrusor overactivity | journal = The Urologic Clinics of North America | volume = 33 | issue = 4 | pages = 439–45, vii | date = November 2006 | pmid = 17011379 | doi = 10.1016/j.ucl.2006.06.003 | series = Overactive Bladder }}</ref> Some studies have identified advantages of transdermal oxybutynin over capsules, finding decreased frequency of incontinence episodes and increased average voided volume of urine.<ref name="oxybut">{{cite journal | vauthors = Baldwin CM, Keating GM | title = Transdermal oxybutynin | journal = Drugs | volume = 69 | issue = 3 | pages = 327–337 | year = 2009 | pmid = 19275276 | doi = 10.2165/00003495-200969030-00008 | s2cid = 33534909 }}</ref>
]
Oxybutynin has been established through head-to-head trials as a more effective for overactive bladder than ], another anticholinergic medication. Specifically, the extended-release form of oxybutynin was found to have greater effect in both the short- and long-term.<ref name=":0" /> However, oxybutynin is not ] for the bladder like tolterodine, and thus has a wider range of side effects. Tolterodine and other anticholinergics are primarily used when clinicians and patients want to reduce the side effect profile.<ref>{{cite journal | vauthors = Loloi J, Clearwater W, Schulz A, Suadicani SO, Abraham N | title = Medical Treatment of Overactive Bladder | journal = The Urologic Clinics of North America | volume = 49 | issue = 2 | pages = 249–261 | date = May 2022 | pmid = 35428431 | doi = 10.1016/j.ucl.2021.12.005 | series = Urologic Pharmacology }}</ref>

Because both drugs have been studied extensively and shown relatively high efficacy, both oxybutynin and tolterodine are considered first-line treatments for overactive bladder. They are thus the typical choices for initial treatment of the condition. The choice of initial therapy often comes down to whether a patient prefers somewhat higher efficacy (oxybutynin) or somewhat reduced side effects (tolterodine).<ref>{{cite journal | vauthors = White N, Iglesia CB | title = Overactive Bladder | journal = Obstetrics and Gynecology Clinics of North America | volume = 43 | issue = 1 | pages = 59–68 | date = March 2016 | pmid = 26880508 | doi = 10.1016/j.ogc.2015.10.002 | series = Medical and Advanced Surgical Management of Pelvic Floor Disorders }}</ref>

=== Hyperhidrosis ===
Since the 2010s, oxybutynin has increasingly been used to treat ] (excessive sweating).<ref>{{cite journal | vauthors = Cruddas L, Baker DM | title = Treatment of primary hyperhidrosis with oral anticholinergic medications: a systematic review | journal = Journal of the European Academy of Dermatology and Venereology | volume = 31 | issue = 6 | pages = 952–963 | date = June 2017 | pmid = 27976476 | doi = 10.1111/jdv.14081 | s2cid = 4535312 }}</ref><ref name=":1">{{cite journal | vauthors = El-Samahy M, Mouffokes A, Badawy MM, Amro S, Fayad T, Abdelwahab OA | title = Safety and efficacy of oxybutynin in patients with hyperhidrosis: systematic review and meta-analysis of randomized controlled trials | journal = Archives of Dermatological Research | volume = 315 | issue = 8 | pages = 2215–2226 | date = October 2023 | pmid = 36869926 | pmc = 10462517 | doi = 10.1007/s00403-023-02587-5 }}</ref> Numerous studies have identified concrete benefits of the drug in treating this condition, but have not identified appropriate ] or the full spectrum of possible ], although ] is seemingly infrequent in patients with hyperhidrosis. Until further clinical trials can be conducted, oxybutynin is only used as an ] for hyperhidrosis (as of 2024).<ref name=":1" />

== Adverse effects ==
Common adverse effects that are associated with oxybutynin and other ] include: ], ], ], ], ], and ].<ref>{{cite book | veditors = Mehta D | date = 2006 | title = ] | volume = 51 | publisher = Pharmaceutical Press | isbn = 0-85369-668-3}}</ref> Anticholinergics have also been known to induce ].<ref>{{cite book | vauthors = Andreasen NC, Black DW | title = Introductory Textbook of Psychiatry | publisher = American Psychiatric Publishing Inc. | date = 2006 }}</ref>

Oxybutynin's tendency to reduce sweating can be dangerous. Reduced sweating increases the risk of ] and ] in apparently safe situations where normal sweating keeps others safe and comfortable.<ref>{{cite web | url = https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011534/?report=details#warning|title=Oxybutynin (By mouth) | publisher = U.S. National Library of Medicine | work = PubMed Health | id = mmdn/DNX0064 }}</ref> Adverse effects of ] are more likely for the elderly and for those with health issues, especially ].<ref>{{cite journal | vauthors = White AT, Vanhaitsma TA, Vener J, Davis SL | title = Effect of passive whole body heating on central conduction and cortical excitability in multiple sclerosis patients and healthy controls | journal = Journal of Applied Physiology | volume = 114 | issue = 12 | pages = 1697–1704 | date = June 2013 | pmid = 23599395 | pmc = 3680823 | doi = 10.1152/japplphysiol.01119.2012 }}</ref>

''N''-Desethyloxybutynin is an ] of oxybutynin that is thought responsible for much of the adverse effects associated with the use of oxybutynin.<ref>{{cite journal | vauthors = Reitz AB, Gupta SK, Huang Y, Parker MH, Ryan RR | title = The preparation and human muscarinic receptor profiling of oxybutynin and N-desethyloxybutynin enantiomers | journal = Medicinal Chemistry | volume = 3 | issue = 6 | pages = 543–545 | date = November 2007 | pmid = 18045203 | doi = 10.2174/157340607782360353 }}</ref> ''N''-Desethyloxybutynin plasma levels may reach as much as six times that of the parent drug after administration of the immediate-release oral formulation.<ref>{{cite journal | vauthors = Zobrist RH, Schmid B, Feick A, Quan D, Sanders SW | title = Pharmacokinetics of the R- and S-enantiomers of oxybutynin and N-desethyloxybutynin following oral and transdermal administration of the racemate in healthy volunteers | journal = Pharmaceutical Research | volume = 18 | issue = 7 | pages = 1029–1034 | date = July 2001 | pmid = 11496941 | doi = 10.1023/a:1010956832113 | s2cid = 8004795 }}</ref> Alternative dosage forms have been developed in an effort to reduce blood levels of ''N''-desethyloxybutynin and achieve a steadier concentration of oxybutynin than is possible with the instant-release form. The long-acting formulations also allow once-daily administration instead of the twice-daily dosage required with the immediate-release form. The transdermal patch, in addition to the benefits of the extended-release oral formulations, bypasses the ] that the oral formulations are subject to.<ref>{{cite journal | vauthors = Oki T, Toma-Okura A, Yamada S | title = Advantages for transdermal over oral oxybutynin to treat overactive bladder: Muscarinic receptor binding, plasma drug concentration, and salivary secretion | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 316 | issue = 3 | pages = 1137–1145 | date = March 2006 | pmid = 16282521 | doi = 10.1124/jpet.105.094508 | s2cid = 30397079 }}</ref>

== Contraindications ==
{{Unreferenced section|date=March 2024}}
Oxybutynin chloride is contraindicated in patients with untreated narrow angle ], and in patients with untreated narrow anterior chamber angles—since ] may aggravate these conditions. It is also contraindicated in partial or complete obstruction of the gastrointestinal tract, hiatal hernia, ], paralytic ileus, intestinal atony of the elderly or debilitated patient, ], ] complicating ], severe colitis, and ]. It is contraindicated in patients with ] and in patients with unstable cardiovascular status in acute hemorrhage. Oxybutynin chloride is contraindicated in patients who have demonstrated hypersensitivity to the product.

== Pharmacology ==
Sources{{which|date=September 2024}} say the drug is absorbed within one hour and has an elimination half-life of 2 to 5 hours.<ref>{{cite web | url = https://www.drugs.com/pro/oxybutynin.html | title = Oxybutynin | access-date = August 30, 2012 | work = drugs.com }}</ref><ref name="pubmed3234461">{{cite journal | vauthors = Douchamps J, Derenne F, Stockis A, Gangji D, Juvent M, Herchuelz A | title = The pharmacokinetics of oxybutynin in man | journal = European Journal of Clinical Pharmacology | volume = 35 | issue = 5 | pages = 515–520 | year = 1988 | pmid = 3234461 | doi = 10.1007/bf00558247 | s2cid = 33628778 }}</ref> There is a wide variation among individuals in the drug's concentration in blood. This, and its low concentration in urine, suggest that it is eliminated through the liver.<ref name="pubmed3234461" />

=== Chemistry ===
Oxybutynin contains one ]. Commercial formulations are sold as the ]. The ] is a more potent anticholinergic than either the racemate or the (''S'')-enantiomer, which is essentially without anticholinergic activity at doses used in clinical practice.<ref>{{cite journal | vauthors = Kachur JF, Peterson JS, Carter JP, Rzeszotarski WJ, Hanson RC, Noronha-Blob L | title = R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 247 | issue = 3 | pages = 867–872 | date = December 1988 | pmid = 2849672 }}</ref><ref>{{cite journal | vauthors = Noronha-Blob L, Kachur JF | title = Enantiomers of oxybutynin: in vitro pharmacological characterization at M1, M2 and M3 muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 256 | issue = 2 | pages = 562–567 | date = February 1991 | pmid = 1993995 }}</ref> However, (''R'')-oxybutynin administered alone offers little or no clinical benefit above and beyond the racemic mixture. The other actions (calcium antagonism, local anesthesia) of oxybutynin are not stereospecific. (''S'')-Oxybutynin has not been clinically tested for its spasmolytic effects, but may be clinically useful for the same indications as the racemate, without the unpleasant anticholinergic side effects.

{| class="wikitable" style="text-align:center"
|- class="hintergrundfarbe6"
! colspan="2"| Enantiomers of oxybutynin
|-
| ]<br /><small> CAS-Number: 119618-21-2</small>
| ]<br /><small> CAS-Number: 119618-22-3</small>
|}

== Society and culture ==
=== Brand names ===
Oxybutynin is available by mouth in generic formulation and under the brand names Ditropan,<ref>{{cite web | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/017577s034,018211s017,020897s018lbl.pdf | title=DITROPAN®(oxybutynin chloride) Tablets and Syrup |publisher=FDA |date=February 2008 |access-date=June 18, 2020}}</ref> Lyrinel XL, Ditrospam, Kentera,<ref>{{Cite web |title=Oxybutynin – Brand names: Ditropan, Lyrinel, Kentera |website=NHS UK |date=June 15, 2021 |url=https://www.nhs.uk/medicines/oxybutynin/}}</ref> and Aquiette,<ref name=concerns>{{Cite journal |title=Pharmacists express concerns over proposed reclassification of overactive bladder drug | vauthors = Robinson J |journal=The Pharmaceutical Journal |date=April 26, 2022 |url=https://pharmaceutical-journal.com/article/news/pharmacists-express-concerns-over-proposed-reclassification-of-overactive-bladder-drug}}</ref> as a transdermal patch under the brand name Oxytrol, and as a ] under the brand name Gelnique.

== Research ==
A large study linked the development of dementia in those over 65 to the use of oxybutynin, due to its ] properties.<ref>{{cite journal | vauthors = Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB | title = Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study | journal = JAMA Internal Medicine | volume = 175 | issue = 3 | pages = 401–407 | date = March 2015 | pmid = 25621434 | pmc = 4358759 | doi = 10.1001/jamainternmed.2014.7663 }}</ref>

== References ==
{{Reflist}}

{{Urologicals}}
{{Hallucinogens}}
{{Muscarinic acetylcholine receptor modulators}}
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