Beyond the Abstract - An overview of the clinical use of antimuscarinics in the treatment of overactive bladder, by A. Athanasopoulos, MD, PhD

BERKELEY, CA (UroToday.com) -

Medical treatment of overactive bladder, current and future treatments

The current English literature on the efficacy, suitability and safety of present and future treatments was reviewed by searching Medline/PubMed for relevant articles published between 1980 and 2010. This was an extensive review but not a systematic one. Moreover the search was limited to relevant articles published in the English language.

During the storage phase, the detrusor contracts spontaneously as a result of the intrinsic activity of the myocyte or of small units of smooth muscle cells. Probably during the storage phase, acetylcholine is still released from the nerves or from a non-neurogenic source like urothelium. Antimuscarinics competitively block muscarinic receptors of all subtypes. Nowadays there is increasing evidence that these drugs also have an important effect on afferent pathways . Tolterodine, solifenacin , darifenacin , trospium chloride and fesoterodine are antimuscarinic agents. Oxybutynin, in addition to having antimuscarinic action, in high dose in vitro exerts muscle-relaxant and local anaesthetic effects while propiverine also in high concentration is an inhibitor of L-type Ca channels. Generally speaking, antimuscarinic agents are safe, with mild adverse effects. The most common reason for treatment discontinuation is dry mouth. Antimuscarinic drugs administered at clinically recommended doses have little effect on voiding pressure and probably act mainly during the bladder storage phase, at which time there is normally no parasympathetic outflow from the spinal cord. Antimuscarinic agents, as a class, offer considerable amelioration, making many patients continent and providing considerable improvements in quality of life. Regarding efficacy, each antimuscarinic drug is effective based on one or more of the outcome measures included in the different clinical trials. Unfortunately it seems that many patients do not complain with the long-term treatment.

Imipramine seems to be a useful drug in the treatment of overactive bladder, especially when combined with antimuscarinic agents, but the risk and benefits of this drug in the treatment of this condition have not yet been adequately assessed. Desmopresin is a synthetic vasopressin analogue with potent antidiuretic effects. The control of nocturnal polyuria with this drug, when indicated, indirectly helps the improvement of nocturia, which is a bothersome symptom of overactive bladder.

Three b-AR subtypes, b1, b2, and b3 have been identified in the detrusor and urothelium of most species, the most prevalent one in human detrusor muscle being b3-AR. Two b3-AR agonists, YM-178 (mirabegron) and GW-427353 been brought to clinical trials. According to one clinical trial, YM178 seems to be efficacious and well-tolerated, headache and gastrointestinal complaints being the most common side effects. YM178 is, therefore, a promising new drug for overactive bladder treatment.

Drugs stimulating the generation of cAMP and increasing bladder NO are known to relax the detrusor smooth muscles. Actually, the eventual utility of PDE5 inhibitors in women with overactive bladder and in men without BPH and erectile dysfunction is still unknown until further studies are conducted.

Other compounds, for example, transient receptor potential vanilloid type 1 (TRPV1), neurokinin receptor antagonists, K+ channel blockers, purinergic receptor antagonists, neurotrophin sequestration, Trk receptor antagonists, prostaglandins and substances controlling intracellular pathways, still have uncertain futures.

Botulinum toxin type A, as a minimally invasive technique, it will always be looked as a second line treatment to be utilized after the failure of oral options.

Written by:
A. Athanasopoulos, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

 

An overview of the clinical use of antimuscarinics in the treatment of overactive bladder - Abstract

UroToday.com Overactive Bladder (OAB) Section

Read other Beyond The Abstract submissions

More Information about Beyond the Abstract

Pelvic Health Weekly Newsletter