Oxybutynin
Encyclopedia
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, as a transdermal patch under the brand name Oxytrol, and as a topical gel under the brand name Gelnique. Also Ditrospam by Avenzor Syria.
Oxybutynin is also a possible treatment of hyperhidrosis
, or hyper-active sweating.
. 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.
, constipation, blurred vision, drowsiness and dizziness. Anticholinergics have also been known to induce delirium
. 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 and calcium defects. An intake of calcium of 800 to 1000 mg is suggested. 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 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. In those with overflow incontinence due to diabetes or neurological diseases like multiple sclerosis or spinal cord trauma, oxybutin can worsen overflow incontinence since the fundamental problem is the bladder is not contracting.
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).
, 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.
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
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
Competitive antagonist
A competitive antagonist is a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor...
antagonizes
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
the M1
Muscarinic acetylcholine receptor M1
The muscarinic acetylcholine receptor M1, also known as the cholinergic receptor, muscarinic 1, is a muscarinic receptor.This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve, is common in exocrine glands and in the CNS.It is predominantly found bound to G proteins...
, M2
Muscarinic acetylcholine receptor M2
The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine receptor.-Heart:...
, and M3
Muscarinic acetylcholine receptor M3
The muscarinic acetylcholine receptor M3, also known as the cholinergic receptor, muscarinic 3, is a muscarinic acetylcholine receptor. It is encoded by the human gene CHRM3....
subtypes of the muscarinic acetylcholine receptor
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
. 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, as a transdermal patch under the brand name Oxytrol, and as a topical gel under the brand name Gelnique. Also Ditrospam by Avenzor Syria.
Oxybutynin is also a possible treatment of hyperhidrosis
Hyperhidrosis
Hyperhidrosis is the condition characterized by abnormally increased perspiration, in excess of that required for regulation of body temperature.-Classification:Hyperhidrosis can either be generalized or localized to specific parts of the body...
, or hyper-active sweating.
Chemistry
Oxybutynin contains one stereocenterChirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
. Commercial formulations are sold as the racemate
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
. The (R)-enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
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.
Clinical efficacy
In two trials of patients with overactive bladder, transdermal oxybutynin 3.9mg/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.Adverse effects
Common adverse effects associated with oxybutynin and other anticholinergics include: dry mouth, difficulty in urinationUrination
Urination, also known as micturition, voiding, peeing, weeing, pissing, and more rarely, emiction, is the ejection of urine from the urinary bladder through the urethra to the outside of the body. In healthy humans the process of urination is under voluntary control...
, constipation, blurred vision, drowsiness and dizziness. Anticholinergics have also been known to induce delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
. 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 and calcium defects. An intake of calcium of 800 to 1000 mg is suggested. 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 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
First pass effect
The first-pass effect is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall...
that the oral formulations are subject to. In those with overflow incontinence due to diabetes or neurological diseases like multiple sclerosis or spinal cord trauma, oxybutin can worsen overflow incontinence since the fundamental problem is the bladder is not contracting.
Clinical pharmacology
Oxybutynin hydrochloride exerts direct antispasmodic effect on smooth muscle and inhibits the muscarinic action of acetylcholine on smooth muscle. It exhibits one-fifth of the anticholinergicAnticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
activity of atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
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).
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 diseaseGastroesophageal reflux disease
Gastroesophageal reflux disease , gastro-oesophageal reflux disease , gastric reflux disease, or acid reflux disease is chronic symptoms or mucosal damage caused by stomach acid coming up from the stomach into the esophagus...
, 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.
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