Oxybutynin

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Oxybutynin
Systematic (IUPAC) name
4-diethylaminobut- 2-ynyl2- cyclohexyl-2- hydroxy-2-phenyl-ethanoate
Identifiers
CAS number	5633-20-5
ATC code	G04BD04
PubChem	4634
DrugBank	APRD00427
Chemical data
Formula	C22H31NO3
Mol. mass	357.486 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	91%-93%
Metabolism	?
Half life	12.4-13.2 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

Oxybutynin 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. 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. It is available orally in generic formulation and as the brand-names Ditropan® and Lyrinel XL®, and as a transdermal patch under the brand-name Oxytrol®.

Oxybutynin also shows promise for treatment of hyperhidrosis, or hyper-active sweating.

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 the doses used in clinical practice. 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.

[edit] Adverse effects

Adverse effects can limit the use of oxybutynin, but can be reduced through the use of modified release preparations (e.g. Lyrinel® XL) or by slowly increasing dosage.

Common adverse effects associated with oxybutynin and other anticholinergics include: dry mouth, difficulty in micturition, constipation, blurred vision, drowsiness and dizziness (Mehta, 2006). 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 due to side effects. 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.

N-desethyloxybutynin is an active metabolite of oxybutynin that is thought to be responsible for much of the adverse effects associated with the use of oxybutynin. N-desethyloxybutynin plasma levels may reach as much as six times that of the parent drug after administration of the immediate-release oral formulation. Alternative dosage forms have been developed in an effort to reduce blood levels of N-desethyloxybutynin and allow for a more steady concentration of oxybutynin to be achieved than is possible with the immediate release form. The long-acting formulations also allow once-daily administration instead of the twice-daily doseage 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.

[edit] References

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

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.

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

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.

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.

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.

v • d • e Urologicals (G04)
Acidifiers	Ammonium chloride, Calcium chloride
Urinary antispasmodics	Darifenacin, Emepronium, Flavoxate, Meladrazine, Oxybutynin, Propiverine, Solifenacin, Terodiline, Tolterodine, Trospium
For erectile dysfunction	Alprostadil, Apomorphine, Avanafil, Moxisylyte, Papaverine, Phentolamine, Sildenafil, Tadalafil, Udenafil, Vardenafil, Vendafidel, Yohimbine
Other urologicals	Acetohydroxamic acid, Collagen, Dimethyl sulfoxide, Magnesium hydroxide, Phenazopyridine, Phenyl salicylate, Succinimide
For benign prostatic hypertrophy	5α-reductase inhibitors: Dutasteride, Finasteride Alpha blockers: Alfuzosin, Doxazosin, Tamsulosin, Terazosin Herbals: Pygeum africanum, Serenoa repens