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Oxybutynin (Ditropan, Lyrinel XL, Lenditro (South Africa)) is an anticholinergic medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination (urge incontinence), by decreasing muscle spasms of the bladder.^[1]

It competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine receptor. It also has direct spasmolytic effects on bladder smooth muscle as a calcium antagonist and local anesthetic, but at concentrations far above those used clinically.

Oxybutynin is also a possible treatment of hyperhidrosis (hyper-active sweating).^[2]^[3]^[4]

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.^[5]^[6] 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.

Clinical efficacy

In two trials of patients with overactive bladder, transdermal oxybutynin 3.9 mg/day decreased the number of incontinence episodes and increased average voided volume to a significantly greater extent than placebo. There was no difference in transdermal oxybutynin and extended-release oral tolterodine.^[7]

Adverse effects

Common adverse effects associated with oxybutynin and other anticholinergics include: dry mouth, difficulty in urination, constipation, blurred vision, drowsiness, and dizziness.^[8] Anticholinergics have also been known to induce delirium.^[9]

These are dose-related and sometimes severe. In one population studied—after six months, more than half of the patients had stopped taking the medication because of side effects and calcium defects. An intake of calcium of 800 to 1000 mg is suggested.^{[citation needed]} Dry mouth may be particularly severe; one estimate is that over a quarter of patients who begin oxybutynin treatment may have to stop because of dry mouth.^{[citation needed]}

N-Desethyloxybutynin is an active metabolite of oxybutynin that is thought responsible for much of the adverse effects associated with the use of oxybutynin.^[10] N-Desethyloxybutynin plasma levels may reach as much as six times that of the parent drug after administration of the immediate-release oral formulation.^[11] 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.^[12] 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.

Clinical pharmacology

Oxybutynin chloride exerts direct antispasmodic effect on smooth muscle and inhibits the muscarinic action of acetylcholine on smooth muscle. It exhibits one-fifth of the anticholinergic activity of atropine on the rabbit detrusor muscle, but four to ten times the antispasmodic activity. No blocking effects occur at skeletal neuromuscular junctions or autonomic ganglia (antinicotinic effects).

Sources say the drug is absorbed within one hour and has an elimination half-life of 2 to 5 hours.^[13]^[14]^[15] 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.^[14]

Contraindications

Oxybutynin chloride is contraindicated in patients with untreated angle closure 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.

Formulations

It is available orally in generic formulation or as the brand-names Ditropan, Lyrinel XL, or Ditrospam, as a transdermal patch under the brand name Oxytrol, and as a topical gel under the brand name Gelnique.

A 2009 Weill Cornell Medical College study concluded that patients switched to generic oxybutynin experienced a degradation in therapeutic value: "In women, there was a doubling of daytime frequency of urination, a slight 20% increase in nocturia, and a 46.3% increase in urge incontinence. In men, there was a 2.4-fold increase in daytime frequency, a 40% increase in nocturia, and a 40.6% increase in urge incontinence".^[16]

References

^ Chapple CR. "Muscarinic receptor antagonists in the treatment of overactive bladder". Urology (55)5, Supp. 1:33-46, 2000.
^ Tupker RA, Harmsze AM, Deneer VH (2006). "Oxybutynin therapy for generalized hyperhidrosis.". Arch Dermatol 142 (8): 1065–6. doi:10.1001/archderm.142.8.1065. PMID 16924061.
^ Mijnhout GS, Kloosterman H, Simsek S, Strack van Schijndel RJ, Netelenbos JC. (2006). "Oxybutynin: dry days for patients with hyperhidrosis.". Neth J Med 64 (9): 326–8. PMID 17057269.
^ Schollhammer M, Misery L. (2007). "Treatment of hyperhidrosis with oxybutynin.". Arch Dermatol. 143 (4): 544–5. doi:10.1001/archderm.143.4.544. PMID 17438194.
^ Kachur JF, et al. "R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine." Journal of Pharmacology and Experimental Therapeutics 247:867-72, 1988.
^ Noronha-Blob L, Kachur JF. "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 of Pharmacology and Experimental Therapeutics 256:562-7, 1991.
^ Baldwin C, Keating GM.[1].Drugs 2009;69 (3):327-337. doi:10.2165/00003495-200969030-00008.
^ Mehta D (Ed.) 2006. British National Formulary 51. Pharmaceutical Press. ISBN 0-85369-668-3
^ Andreasen NC and Black DW, "Introductory Textbook of Psychiatry." American Psychiatric Publishing Inc. 2006
^ Allen B. Reitz, Suneel K. Gupta, Yifang Huang, Michael H. Parker, and Richard R. Ryan (2007). "The preparation and human muscarinic receptor profiling of oxybutynin and N-desethyloxybutynin enantiomers". Med Chem 3 (6): 543–5. doi:10.2174/157340607782360353. PMID 18045203.
^ Zobrist RH, et al. "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 18:1029-1034, 2001.
^ Oki T, et al. "Advantages for Transdermal over Oral Oxybutynin to Treat Overactive Bladder: Muscarinic Receptor Binding, Plasma Drug Concentration, and Salivary Secretion". Journal of Pharmacology and Experimental Therapeutics Fast Forward 316:1137-1145, 2006.
^ [2] "Oxybutynin" Retrieved on 30 August 2012.
^ ^a ^b [3] "The pharmacokinetics of oxybutynin in man. (Abstract)" Retrieved on 30 August 2012.
^ [4] "Oxybutynin" Retrieved on 30 August 2012.
^ Kerr, Martha (2009-05-03). "AUA 2009: Generics Not Equal to Brand-Name Drugs for Overactive Bladder". American Urological Association (AUA) 104th Annual Scientific Meeting (Medscape). Retrieved 2013-04-20.

External links

http://health.yahoo.com/urinary-medications/oxybutynin-oral/healthwise--d00328a1.html
http://www.mayoclinic.com/health/drug-information/DR601047
http://www.medicinenet.com/oxybutynin_er-oral/article.htm

UpToDate Contents

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1. 小児における膀胱機能障害のマネージメント management of bladder dysfunction in children
2. 夜間頻尿：臨床症状、診断、および治療治療 nocturia clinical presentation diagnosis and treatment
3. 女性における尿失禁の治療および予防 treatment and prevention of urinary incontinence in women
4. 男性における下部尿路症状 lower urinary tract symptoms in men
5. 原発性局所多汗症 primary focal hyperhidrosis

English Journal

Stimulation of large-conductance calcium-activated potassium channels inhibits neurogenic contraction of human bladder from patients with urinary symptoms and reverses acetic acid-induced bladder hyperactivity in rats.

La Fuente JM1, Fernández A2, Cuevas P2, González-Corrochano R3, Chen MX4, Angulo J5.
European journal of pharmacology.Eur J Pharmacol.2014 Jul 15;735:68-76. doi: 10.1016/j.ejphar.2014.03.060. Epub 2014 Apr 18.
We have analysed the effects of large-conductance calcium-activated potassium channel (BK) stimulation on neurogenic and myogenic contraction of human bladder from healthy subjects and patients with urinary symptoms and evaluated the efficacy of activating BK to relief bladder hyperactivity in rats.
PMID 24747752

Association of statin use with storage lower urinary tract symptoms (LUTS): data mining of prescription database.

Fujimoto M, Higuchi T, Hosomi K, Takada M.
International journal of clinical pharmacology and therapeutics.Int J Clin Pharmacol Ther.2014 Jul 2. [Epub ahead of print]
Objective: The efficacy and safety of statins have been studied in a number of clinical trials and epidemiological studies. In recent years, the Medicine and Healthcare Products Regulatory Agency (MHRA) has assessed the evidence available on the following adverse reactions associated with the use of
PMID 24986095

Long-term Results of the Use of Oxybutynin for the Treatment of Axillary Hyperhidrosis.

Wolosker N1, Teivelis MP2, Krutman M3, de Paula RP4, Kauffman P3, de Campos JR1, Puech-Leão P4.
Annals of vascular surgery.Ann Vasc Surg.2014 Jul;28(5):1106-12. doi: 10.1016/j.avsg.2013.12.024. Epub 2014 Feb 8.
BACKGROUND: Axillary hyperhidrosis (AH) is a common disease, with a significant impact on quality of life (QOL). Good short-term results are reported with oxybutynin, but longer follow-up data are lacking. We evaluated its effectiveness in a large series of patients who were not surgically treated a
PMID 24512855

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「オキシブチニン」

Oxybutynin
Systematic (IUPAC) name
	4-Diethylaminobut-2-ynyl 2-cyclohexyl-2-hydroxy-2-phenylethanoate
Clinical data
Trade names	Ditropan
AHFS/Drugs.com	monograph
MedlinePlus	a682141
Pregnancy cat.	AU: B1; US: B;
Legal status	AU: Prescription Only (S4); CA: ℞-only; UK: POM; US: Rx-only/OTC;
Routes	oral, transdermal gel, transdermal patch
Pharmacokinetic data
Protein binding	91%-93%
Half-life	12.4-13.2 hours
Identifiers
CAS number	5633-20-5
ATC code	G04BD04
PubChem	CID 4634
IUPHAR ligand	359
DrugBank	DB01062
ChemSpider	4473
UNII	K9P6MC7092
KEGG	D00465
ChEBI	CHEBI:7856
ChEMBL	CHEMBL1231
Chemical data
Formula	C22H31NO3
Mol. mass	357.486 g/mol
	SMILES O=C(OCC#CCN(CC)CC)C(O)(c1ccccc1)C2CCCCC2;
	InChI 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 ; Key:XIQVNETUBQGFHX-UHFFFAOYSA-N ;
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　　[★]

英: oxybutynin
化: 塩酸オキシブチニン oxybutynin hydrochloride
商: ウルゲント、オリベート、デライブ、ファンデヒーデ、ポスチニン、ポラキス、ポラチール、Ditropan、ネオキシテープ

[1] Chapple CR. "Muscarinic receptor antagonists in the treatment of overactive bladder". Urology (55)5, Supp. 1:33-46, 2000.

[2] Tupker RA, Harmsze AM, Deneer VH (2006). "Oxybutynin therapy for generalized hyperhidrosis.". Arch Dermatol 142 (8): 1065–6. doi:10.1001/archderm.142.8.1065. PMID 16924061.

[3] Mijnhout GS, Kloosterman H, Simsek S, Strack van Schijndel RJ, Netelenbos JC. (2006). "Oxybutynin: dry days for patients with hyperhidrosis.". Neth J Med 64 (9): 326–8. PMID 17057269.

[4] Schollhammer M, Misery L. (2007). "Treatment of hyperhidrosis with oxybutynin.". Arch Dermatol. 143 (4): 544–5. doi:10.1001/archderm.143.4.544. PMID 17438194.

[5] Kachur JF, et al. "R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine." Journal of Pharmacology and Experimental Therapeutics 247:867-72, 1988.

[6] Noronha-Blob L, Kachur JF. "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 of Pharmacology and Experimental Therapeutics 256:562-7, 1991.

[oxybut-7] Baldwin C, Keating GM.[1].Drugs 2009;69 (3):327-337. doi:10.2165/00003495-200969030-00008.

[8] Mehta D (Ed.) 2006. British National Formulary 51. Pharmaceutical Press. ISBN 0-85369-668-3

[9] Andreasen NC and Black DW, "Introductory Textbook of Psychiatry." American Psychiatric Publishing Inc. 2006

[10] Allen B. Reitz, Suneel K. Gupta, Yifang Huang, Michael H. Parker, and Richard R. Ryan (2007). "The preparation and human muscarinic receptor profiling of oxybutynin and N-desethyloxybutynin enantiomers". Med Chem 3 (6): 543–5. doi:10.2174/157340607782360353. PMID 18045203.

[11] Zobrist RH, et al. "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 18:1029-1034, 2001.

[12] Oki T, et al. "Advantages for Transdermal over Oral Oxybutynin to Treat Overactive Bladder: Muscarinic Receptor Binding, Plasma Drug Concentration, and Salivary Secretion". Journal of Pharmacology and Experimental Therapeutics Fast Forward 316:1137-1145, 2006.

[13] [2] "Oxybutynin" Retrieved on 30 August 2012.

[pubmed3234461-14] [3] "The pharmacokinetics of oxybutynin in man. (Abstract)" Retrieved on 30 August 2012.

[15] [4] "Oxybutynin" Retrieved on 30 August 2012.

[AUA_2009-16] Kerr, Martha (2009-05-03). "AUA 2009: Generics Not Equal to Brand-Name Drugs for Overactive Bladder". American Urological Association (AUA) 104th Annual Scientific Meeting (Medscape). Retrieved 2013-04-20.

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Ditropan