resiniferatoxin and oxybutynin

The objective of the study was to assess the effectiveness of intravesical treatment for painful bladder syndrome (PBS).. A systematic review was performed until December 31, 2010. The selection criteria included only randomized controlled trials of PBS patients who received intravesical treatment. The primary outcomes measures were clinical and urodynamic parameters. Relative risk and mean differences were used for binary and continuous outcomes respectively, with confidence interval of 95%.. The search strategy identified 770; however, only 28 eligible trials met methodological requirements for complete analysis. Altogether, the review included four treatment modalities: resiniferatoxin, Bacillus Calmette-Guérin (BCG), oxybutynin, and alkalinized lidocaine. Meta-analysis of BCG therapy showed improvement in symptoms according to the Wisconsin Interstitial Cystitis Symptom Inventory, but no difference in 24-h urinary frequency.. Meta-analysis showed an improvement exclusively of the symptoms as measured by the Wisconsin Interstitial Cystitis Inventory, but not in 24-h urinary frequency, with BCG therapy. Further randomized clinical trials, including trials of more recent drugs, are required for evaluation of intravesical therapies for PBS.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Anesthetics, Local; BCG Vaccine; Cystitis, Interstitial; Diterpenes; Humans; Lidocaine; Mandelic Acids; Muscarinic Antagonists; Neurotoxins

A few decades ago, urinary diversion, usually with an ileal conduit, was the ultimate outcome for most children with spina bifida. The revolutionary institution of clean intermittent catheterization has changed the algorithm totally. Furthermore many new drugs have been developed during the past decade and have decreased the need for surgery dramatically. In this article, we will focus on the most recent data on new modalities of therapy to help avoid urinary diversion or bladder augmentation.. In addition to clean intermittent catheterization and oxybutynin treatment, a new generation of anticholinergic medications, such as tolterodine, has been developed. For patients who drop out because of the side-effects of oral administration, new methods of administration are now available, including extended release and intravesical instillation. For those unresponsive, botulinum-A toxin and resiniferatoxin are two relatively new drugs in the field, administered as intravesical injection and instillation, respectively. Intravesical or transdermal electrical stimulation, sacral nerve stimulation and biofeedback therapy are under development, but as currently administered, are not yet completely successful.. Although life-saving in many respects, bladder augmentation introduces life-long risks of its own. Our goal in describing 'conservative' management is to prevent this step. Many alternatives to surgery are available now and more effective strategies are under development.

Topics: Anti-Dyskinesia Agents; Benzhydryl Compounds; Biofeedback, Psychology; Botulinum Toxins; Child; Child, Preschool; Cholinergic Antagonists; Cresols; Diterpenes; Electric Stimulation Therapy; Humans; Infant; Infant, Newborn; Mandelic Acids; Meningomyelocele; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Catheterization

Topics: Administration, Intravesical; Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Botulinum Toxins; Capsaicin; Cholinergic Antagonists; Cresols; Cystitis, Interstitial; Diterpenes; Humans; Mandelic Acids; Neurotoxins; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder Diseases; Urination Disorders

Intravesical agents for overactive bladder have mostly been used in patients with neurogenic bladder disorders. The patients have usually had severe detrusor hyperreflexia (DH) plus a disorder of bladder emptying, and because of residual urine have been performing intermittent self-catheterization. Intravesical medication has therefore been appropriate. Strategies for treating DH have been either to lessen the parasympathetic efferent activity or to de-afferent the bladder. Two types of treatment have been used: intravesical medications that block pelvic nerve-detrusor smooth muscle cholinergic transmission, or agents that block the afferent arm of the reflex that causes detrusor contraction. Intravesical oxybutynin is thought to have some local anesthetic effect, although its main mode of action is to block cholinergic transmission. It has been demonstrated to be effective in resistant DH. Intravesical atropine has been demonstrated to increase bladder capacity but its usefulness in the clinical management of DH has yet to be demonstrated. Local anesthetics can increase bladder capacity, but the effect is short-lived. Longer-acting agents may have a selective neurotoxic effect on capsaicin-sensitive bladder afferents. Many patients worldwide have now been treated with intravesical capsaicin. Resiniferatoxin (RTX) is an ultrapotent capsaicin analog that has the significant advantage of being a nonirritant. Intravesical agents appear to be attractive alternatives to oral medication and hold the exciting possibility of selectively targeting end organs implicated in pathophysiologic responses.

Topics: Administration, Intravesical; Anesthetics, Local; Atropine; Capsaicin; Cholinergic Antagonists; Diterpenes; Humans; Mandelic Acids; Neurons, Afferent; Neurotoxins; Urinary Bladder Diseases; Urinary Incontinence

The use of liposomes for drug release has demonstrated to be a promising therapeutic platform for biomedical applications. In this study, intravesical administration of OXI (1.5 mM) and RTX (100 nM) was used to compare histological changes caused in Wistar female rats by the drugs both unloaded and loaded in liposomes. After instillation of formulations by intravesical catheter, bladders were removed and histological analysis carried out at pre-determined time intervals over a period of 60 days. Urinalysis was performed to verify the presence of infection and of liposomes. Results showed that RTX caused a higher bladder damage, with inflammatory reaction that reached all bladder layers. After 60 days, RTX-treated group showed urothelial alterations, collagen replacement by fibrosis and also abdominal adherence, but not the OXI-treated group. At the end of the assay, the liposomal-treated groups showed a minimal inflammatory reaction and significantly increased bladder size. Moreover, urinalysis confirmed the presence of liposomes in rat urine. RTX promoted higher bladder damage than OXI. Intravesical administration of liposomal OXI or RTX formulations minimized inflammatory reaction, with an extended drug effect on bladders. After a single intravesical administration, liposomes were found in rat urine samples after 60 days.

Topics: Animals; Diterpenes; Drug Tolerance; Female; Liposomes; Mandelic Acids; Rats; Rats, Wistar