Oxybutynin

Last updated

Oxybutynin
Oxybutynin.svg
Oxybutynin 3d balls.png
Clinical data
Trade names Ditropan, Gelnique, others
AHFS/Drugs.com Monograph
MedlinePlus a682141
License data
Pregnancy
category
  • AU:B1
Routes of
administration 		Oral, transdermal
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 91–93%
Elimination half-life 12.4–13.2 hours
Identifiers
  • 4-Diethylaminobut-2-ynyl 2-cyclohexyl-2-hydroxy-2-phenylethanoate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.158.590 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H31NO3
Molar mass 357.494 g·mol−1
3D model (JSmol)
  • O=C(OCC#CCN(CC)CC)C(O)(c1ccccc1)C2CCCCC2
  • InChI=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 Yes check.svgY
  • Key:XIQVNETUBQGFHX-UHFFFAOYSA-N Yes check.svgY
   (verify)

Oxybutynin, sold as under the brand name Ditropan among others, is an anticholinergic drug primarily used to treat overactive bladder. It is widely considered a first-line therapy 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 tolterodine, darifenacin, and solifenacin, although it is usually preferred over these medications. It is sometimes used off-label for treatment of hyperhidrosis, or excessive sweating. It has also been used off-label to treat bed wetting in children, but this use has declined, as it is most likely ineffective in this role. It is taken by mouth or applied to the skin.

Contents

Common side effects include dry mouth, constipation, dizziness, trouble sleeping, and urinary tract infections. [1] Serious side effects may include urinary retention and an increased risk of heat stroke. [1] Use in pregnancy appears safe but has not been well studied while use in breastfeeding is of unclear safety. [2] It is an antimuscarinic and works by blocking the effects of acetylcholine on smooth muscle. [1]

Oxybutynin was approved for medical use in the United States in 1975. [1] It is available as a generic medication. [3] In 2021, it was the 102nd most commonly prescribed medication in the United States, with more than 6 million prescriptions. [4] [5]

Medical use

Oxybutynin is used in the form of standard-release capsules, extended-release capsules, or transdermal (topical) products. All of these are considered safe and effective options for treatment of detrusor muscle-mediated overactive bladder. [1] Extended-release formulations decrease the number of weekly incontinence episodes by an average of 90% compared to an untreated state. [6] Some studies have identified advantages of transdermal oxybutynin over capsules, finding decreased frequency of incontinence episodes and increased average voided volume of urine. [7]

Oxybutynin is superior to other anticholinergics for treatment of overactive bladder. Oxybutynin and Tolterodine in treating overactive bladder.png
Oxybutynin is superior to other anticholinergics for treatment of overactive bladder.

Oxybutynin has been established through head-to-head trials as a more effective for overactive bladder than tolterodine, another anticholinergic medication. Specifically, the extended release form of oxybutynin was found to have greater effect in both the short- and long-term. [6] However, oxybutynin is not selective 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. [8]

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). [9]

Hyperhidrosis

Since the 2010s, oxybutynin has increasingly been used to treat hyperhidrosis (excessive sweating). [10] [11] Numerous studies have identified concrete benefits of the drug in treating this condition, but have not identified appropriate dosing or the full spectrum of possible side effects, although dry mouth is seemingly infrequent in patients with hyperhidrosis. Until further clinical trials can be conducted, oxybutynin is only used as an off-label medication for hyperhidrosis (as of 2024). [11]

Adverse effects

Common adverse effects that are associated with oxybutynin and other anticholinergics include: dry mouth, difficulty in urination, constipation, blurred vision, drowsiness, and dizziness. [12] Anticholinergics have also been known to induce delirium. [13]

Oxybutynin's tendency to reduce sweating can be dangerous. Reduced sweating increases the risk of heat exhaustion and heat stroke in apparently safe situations where normal sweating keeps others safe and comfortable. [14] Adverse effects of elevated body temperature are more likely for the elderly and for those with health issues, especially multiple sclerosis. [15]

N-Desethyloxybutynin is an active metabolite of oxybutynin that is thought responsible for much of the adverse effects associated with the use of oxybutynin. [16] N-Desethyloxybutynin plasma levels may reach as much as six times that of the parent drug after administration of the immediate-release oral formulation. [17] 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 immediate 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 first-pass hepatic effect that the oral formulations are subject to. [18] In those with overflow incontinence because of diabetes or neurological diseases like multiple sclerosis or spinal cord trauma, oxybutynin can worsen overflow incontinence since the fundamental problem is that the bladder is not contracting.

A large study linked the development of dementia in those over 65 to the use of oxybutynin, due to its anticholinergic properties. [19]

Contraindications

Oxybutynin chloride is contraindicated in patients with untreated narrow angle glaucoma, and in patients with untreated narrow anterior chamber angles—since anticholinergic drugs may aggravate these conditions. It is also contraindicated in partial or complete obstruction of the gastrointestinal tract, hiatal hernia, gastroesophageal reflux disease, paralytic ileus, intestinal atony of the elderly or debilitated patient, megacolon, toxic megacolon complicating ulcerative colitis, severe colitis, and myasthenia gravis. It is contraindicated in patients with obstructive uropathy 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 say the drug is absorbed within one hour and has an elimination half-life of 2 to 5 hours. [20] [21] 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. [21]

Chemistry

Oxybutynin contains one stereocenter. Commercial formulations are sold as the racemate. The (R)-enantiomer 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. [22] [23] 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.

Enantiomers of oxybutynin
(R)-Oxybutynin Structural Formula V1.svg
CAS-Number: 119618-21-2		 (S)-Oxybutynin Structural Formula V1.svg
CAS-Number: 119618-22-3

Brand names

Oxybutynin is available by mouth in generic formulation and under the brand names Ditropan, [24] Lyrinel XL, Ditrospam, Kentera, [25] and Aquiette, [26] as a transdermal patch under the brand name Oxytrol, and as a topical gel under the brand name Gelnique.

Related Research Articles

<span class="mw-page-title-main">Urinary incontinence</span> Uncontrolled leakage of urine

Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geriatric health care. The term enuresis is often used to refer to urinary incontinence primarily in children, such as nocturnal enuresis. UI is an example of a stigmatized medical condition, which creates barriers to successful management and makes the problem worse. People may be too embarrassed to seek medical help, and attempt to self-manage the symptom in secrecy from others.

Anticholinergics are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central and peripheral nervous system.

<span class="mw-page-title-main">Ipratropium bromide</span> Type of anticholinergic

Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons.

<span class="mw-page-title-main">Hyperhidrosis</span> Excessive sweating

Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psychological, emotional, and social perspective. In fact, hyperhidrosis almost always leads to psychological as well as physical and social consequences. People suffering from it present difficulties in the professional field, more than 80% experiencing a moderate to severe emotional impact from the disease and half are subject to depression.

<span class="mw-page-title-main">Glycopyrronium bromide</span> Chemical compound

Glycopyrronium bromide is a medication of the muscarinic anticholinergic group. It does not cross the blood–brain barrier and consequently has few to no central effects. It is given by mouth, via intravenous injection, on the skin, and via inhalation. It is a synthetic quaternary ammonium compound. The cation, which is the active moiety, is called glycopyrronium (INN) or glycopyrrolate (USAN).

<span class="mw-page-title-main">Tolterodine</span> Benzhydryl compound

Tolterodine, sold under the brand name Detrol among others, is a medication used to treat frequent urination, urinary incontinence, or urinary urgency. Effects are seen within an hour. It is taken by mouth.

<span class="mw-page-title-main">Orphenadrine</span> Muscle relaxant drug

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. It is considered a dirty drug due to its multiple mechanisms of action in different pathways. It was discovered and developed in the 1940s.

<span class="mw-page-title-main">Chlorprothixene</span> Typical antipsychotic medication

Chlorprothixene, sold under the brand name Truxal among others, is a typical antipsychotic of the thioxanthene group.

Percutaneous tibial nerve stimulation (PTNS), also referred to as posterior tibial nerve stimulation, is the least invasive form of neuromodulation used to treat overactive bladder (OAB) and the associated symptoms of urinary urgency, urinary frequency and urge incontinence. These urinary symptoms may also occur with interstitial cystitis and following a radical prostatectomy. Outside the United States, PTNS is also used to treat fecal incontinence.

<span class="mw-page-title-main">Darifenacin</span> Medication for urinary incontinence

Darifenacin is a medication used to treat urinary incontinence due to an overactive bladder. It was discovered by scientists at the Pfizer research site in Sandwich, UK under the identifier UK-88,525 and used to be marketed by Novartis. In 2010, the US rights were sold to Warner Chilcott for US$400 million.

<span class="mw-page-title-main">Solifenacin</span> Chemical compound

Solifenacin, sold as the brand name Vesicare among others, is a medicine used to treat overactive bladder and neurogenic detrusor overactivity (NDO). It may help with incontinence, urinary frequency, and urinary urgency.

<span class="mw-page-title-main">Trospium chloride</span> Chemical compound

Trospium chloride is a muscarinic antagonist used to treat overactive bladder. It has side effects typical of this class of drugs, namely dry mouth, stomach upset, and constipation; these side effects cause problems with people taking their medicine as directed. However it doesn't cause central nervous system side effects like some other muscarinic antagonists. It is in pregnancy category C and is excreted in breast milk.

<span class="mw-page-title-main">Overactive bladder</span> Condition where a person has a frequent need to urinate

Overactive bladder (OAB) is a common condition where there is a frequent feeling of needing to urinate to a degree that it negatively affects a person's life. The frequent need to urinate may occur during the day, at night, or both. Loss of bladder control may occur with this condition. This condition is also sometimes characterized by a sudden and involuntary contraction of the bladder muscles, in response to excitement or anticipation. This in turn leads to a frequent and urgent need to urinate.

<span class="mw-page-title-main">Bornaprine</span> Chemical compound

Bornaprine is a synthetic anticholinergic medication that is primarily used to treat Parkinson's disease. Additionally, bornaprine has been used to treat other disorders, including hyperhidrosis.

<span class="mw-page-title-main">Meclizine</span> Chemical compound

Meclizine, sold under the brand name Bonine, among others, is an antihistamine used to treat motion sickness and dizziness (vertigo). It is taken by mouth. Effects generally begin in an hour and last for up to a day.

Mirabegron, sold under the brand name Myrbetriq among others, is a medication used to treat overactive bladder. Its benefits are similar to antimuscarinic medication such as solifenacin or tolterodine. It is taken by mouth.

<span class="mw-page-title-main">Methoctramine</span> Chemical compound

Methoctramine is a polymethylene tetraamine that acts as a muscarinic antagonist. It preferentially binds to the pre-synaptic receptor M2, a muscarinic acetylcholine ganglionic protein complex present basically in heart cells. In normal conditions -absence of methoctramine-, the activation of M2 receptors diminishes the speed of conduction of the sinoatrial and atrioventricular nodes thus reducing the heart rate. Thanks to its apparently high cardioselectivity, it has been studied as a potential parasymphatolitic drug, particularly against bradycardia. However, currently it is only addressed for research purposes, since the administration to humans is still unavailable.

<span class="mw-page-title-main">Vibegron</span> Medication

Vibegron, sold under the brand name Gemtesa, is a medication for the treatment of overactive bladder. Vibegron is a selective beta-3 adrenergic receptor agonist.

<span class="mw-page-title-main">Cholinergic blocking drug</span> Drug that block acetylcholine in synapses of cholinergic nervous system

Cholinergic blocking drugs are a group of drugs that block the action of acetylcholine (ACh), a neurotransmitter, in synapses of the cholinergic nervous system. They block acetylcholine from binding to cholinergic receptors, namely the nicotinic and muscarinic receptors.

<span class="mw-page-title-main">Sofpironium bromide</span> Chemical compound

Sofpironium bromide is a drug used to treat hyperhidrosis. It was approved in Japan in 2020 as a 5% gel for the treatment of primary axillary hyperhidrosis (PAH).

References

  1. 1 2 3 4 5 "Oxybutynin Chloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved March 3, 2019.
  2. ↑ "Oxybutynin Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved March 3, 2019.
  3. ↑ British National Formulary: BNF 76 (76th ed.). Pharmaceutical Press. 2018. ISBN   978-0-85711-338-2.
  4. ↑ "The Top 300 of 2021". ClinCalc. Archived from the original on January 15, 2024. Retrieved January 14, 2024.
  5. ↑ "Oxybutynin - Drug Usage Statistics". ClinCalc. Retrieved January 14, 2024.
  6. 1 2 Diokno A, Ingber M (November 2006). "Oxybutynin in detrusor overactivity". The Urologic Clinics of North America. Overactive Bladder. 33 (4): 439–45, vii. doi:10.1016/j.ucl.2006.06.003. PMID   17011379.
  7. ↑ Baldwin CM, Keating GM (2009). "Transdermal oxybutynin". Drugs. 69 (3): 327–337. doi:10.2165/00003495-200969030-00008. PMID   19275276. S2CID   33534909.
  8. ↑ Loloi J, Clearwater W, Schulz A, Suadicani SO, Abraham N (May 2022). "Medical Treatment of Overactive Bladder". The Urologic Clinics of North America. Urologic Pharmacology. 49 (2): 249–261. doi:10.1016/j.ucl.2021.12.005. PMID   35428431.
  9. ↑ White N, Iglesia CB (March 2016). "Overactive Bladder". Obstetrics and Gynecology Clinics of North America. Medical and Advanced Surgical Management of Pelvic Floor Disorders. 43 (1): 59–68. doi:10.1016/j.ogc.2015.10.002. PMID   26880508.
  10. ↑ Cruddas L, Baker DM (June 2017). "Treatment of primary hyperhidrosis with oral anticholinergic medications: a systematic review". Journal of the European Academy of Dermatology and Venereology. 31 (6): 952–963. doi:10.1111/jdv.14081. PMID   27976476. S2CID   4535312.
  11. 1 2 El-Samahy M, Mouffokes A, Badawy MM, Amro S, Fayad T, Abdelwahab OA (October 2023). "Safety and efficacy of oxybutynin in patients with hyperhidrosis: systematic review and meta-analysis of randomized controlled trials". Archives of Dermatological Research. 315 (8): 2215–2226. doi:10.1007/s00403-023-02587-5. PMC   10462517 . PMID   36869926.
  12. ↑ Mehta D, ed. (2006). British National Formulary . Vol. 51. Pharmaceutical Press. ISBN   0-85369-668-3.
  13. ↑ Andreasen NC, Black DW (2006). Introductory Textbook of Psychiatry. American Psychiatric Publishing Inc.
  14. ↑ "Oxybutynin (By mouth)". PubMed Health. U.S. National Library of Medicine. mmdn/DNX0064.
  15. ↑ White AT, Vanhaitsma TA, Vener J, Davis SL (June 2013). "Effect of passive whole body heating on central conduction and cortical excitability in multiple sclerosis patients and healthy controls". Journal of Applied Physiology. 114 (12): 1697–1704. doi:10.1152/japplphysiol.01119.2012. PMC   3680823 . PMID   23599395.
  16. ↑ Reitz AB, Gupta SK, Huang Y, Parker MH, Ryan RR (November 2007). "The preparation and human muscarinic receptor profiling of oxybutynin and N-desethyloxybutynin enantiomers". Medicinal Chemistry. 3 (6): 543–545. doi:10.2174/157340607782360353. PMID   18045203.
  17. ↑ Zobrist RH, Schmid B, Feick A, Quan D, Sanders SW (July 2001). "Pharmacokinetics of the R- and S-enantiomers of oxybutynin and N-desethyloxybutynin following oral and transdermal administration of the racemate in healthy volunteers". Pharmaceutical Research. 18 (7): 1029–1034. doi:10.1023/a:1010956832113. PMID   11496941. S2CID   8004795.
  18. ↑ Oki T, Toma-Okura A, Yamada S (March 2006). "Advantages for transdermal over oral oxybutynin to treat overactive bladder: Muscarinic receptor binding, plasma drug concentration, and salivary secretion". The Journal of Pharmacology and Experimental Therapeutics. 316 (3): 1137–1145. doi:10.1124/jpet.105.094508. PMID   16282521. S2CID   30397079.
  19. ↑ Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. (March 2015). "Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study". JAMA Internal Medicine. 175 (3): 401–407. doi:10.1001/jamainternmed.2014.7663. PMC   4358759 . PMID   25621434.
  20. ↑ "Oxybutynin". drugs.com. Retrieved August 30, 2012.
  21. 1 2 Douchamps J, Derenne F, Stockis A, Gangji D, Juvent M, Herchuelz A (1988). "The pharmacokinetics of oxybutynin in man". European Journal of Clinical Pharmacology. 35 (5): 515–520. doi:10.1007/bf00558247. PMID   3234461. S2CID   33628778.
  22. ↑ Kachur JF, Peterson JS, Carter JP, Rzeszotarski WJ, Hanson RC, Noronha-Blob L (December 1988). "R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine". The Journal of Pharmacology and Experimental Therapeutics. 247 (3): 867–872. PMID   2849672.
  23. ↑ Noronha-Blob L, Kachur JF (February 1991). "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". The Journal of Pharmacology and Experimental Therapeutics. 256 (2): 562–567. PMID   1993995.
  24. ↑ "DITROPAN®(oxybutynin chloride) Tablets and Syrup" (PDF). FDA. February 2008. Retrieved June 18, 2020.
  25. ↑ "Oxybutynin – Brand names: Ditropan, Lyrinel, Kentera". NHS UK. June 15, 2021.
  26. ↑ Robinson J (April 26, 2022). "Pharmacists express concerns over proposed reclassification of overactive bladder drug". The Pharmaceutical Journal.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.