tolterodine-tartrate and Chronic-Disease

Antimuscarinics (AMs) are the mainstay of pharmacological treatment of overactive bladder (OAB), a symptom complex defined by the presence of urinary urgency, usually associated with frequency and nocturia, with or without urgency urinary incontinence. The AMs used to treat OAB differ in their pharmacological profiles, which may affect their potential for causing adverse effects (AEs).. The present article aims to review the literature about pharmacokinetics (PK) of the different AMs used in the treatment of OAB. Furthermore, the AEs related to the use of these drugs and their incidence are presented. This systematic review is based on material searched and obtained via Medline, Pubmed and EMBASE up to March 2012 using the search terms "adverse events, pharmacokinetics, tolerability" in combination with "darifenacin, fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium.". Antimuscarinics are the first-line pharmacological treatment for OAB. Despite the development of new molecules that improve their efficacy/safety profile, there are some drugs that are pharmacokinetically more appropriate to be prescribed in specific populations such as patients with neurological disease or the elderly. Moreover, research should be encouraged in evaluating antimuscarinics in conjunction with other drugs such as estrogens or beta-agonists. The identification of prognostic criteria for pharmacological therapy would be helpful.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Chronic Disease; Cresols; Drug Combinations; Female; Humans; Imidazoles; Mandelic Acids; Muscarinic Antagonists; Nocturia; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

The aim of the present study was to use an animal model of interstitial cystitis (IC) in order to investigate the histology and function of the bladder, with a particular focus on mast cell degranulation and response to detrusor overactivity (DO) to tolterodine. A total of 18 female Sprague‑Dawley rats were used. In 12 rats, lipopolysaccharide (LPS) was intravesically instilled following the induction of IC by protamine sulfate (PS) and six rats were subjected to sham instillations. Following 1 month, cystometry was performed. The effects of tolterodine were tested in half of the animals with IC. All rats in the IC group demonstrated DO during the filling phase and no significant changes in the frequency or pressure compared with that following tolterodine injection were identified. Histological examination revealed a significant increase in the total number of infiltrated mast cells in IC rats compared with that in the sham rats (P<0.05). Degranulated mast cells were evident in 80% of rats with IC; however, they were not apparent in the sham rats. Urinary bladder inflammation, similar to that in human IC in terms of degranulated mast cells and bladder function, was induced in rats. The animal model used in the present study provided insight into the pathophysiological mechanisms underlying the ineffectiveness of anticholinergics in patients with overlapping IC and overactive bladder (OAB).

Topics: Animals; Benzhydryl Compounds; Chronic Disease; Cresols; Cystitis, Interstitial; Disease Models, Animal; Female; Lipopolysaccharides; Mast Cells; Phenylpropanolamine; Protamines; Rats; Rats, Sprague-Dawley; Tolterodine Tartrate; Urinary Bladder; Urodynamics; Urological Agents

Large, controlled trials in chronic pelvic pain syndrome (CPPS) have failed due to patient heterogeneity. To phenotype CPPS patients, we developed the UPOINT system with 6 domains (Urinary, Psychosocial, Organ-Specific, Infection, Neurologic/Systemic and Tenderness). In this study, we treated patients with multimodal therapy based on the UPOINT phenotype and measured response after at least 6 months.. Patients with CPPS were offered multimodal therapy based on the UPOINT phenotype (eg, Urinary: alpha blocker or antimuscarinic; Organ-specific: quercetin; Tenderness: physical therapy). One hundred patients agreed to therapy and were reexamined after 26 weeks. Primary endpoint was a minimum 6-point drop in NIH-Chronic Prostatitis Symptom Index (CPSI).. Mean age was 46 years, and median symptom duration was 24 months. A median of 3 UPOINT domains were positive, the most common being Organ-specific (70%), Tenderness (64%), and Urinary (59%). With a median 50-week follow-up, 84% had at least a 6-point fall in CPSI. Number of domains and initial CPSI did not predict response. Mean changes (+/-SD) for CPSI subscores were pain 11.5+/-3.2 to 6.1+/-3.9, urine 4.7+/-3.1 to 2.6+/-2.0, QOL 9.1+/-2.3 to 4.5+/-2.8, and total 25.2+/-6.1 to 13.2+/-7.2 (all P<.0001). No domain predicted outcome; however, quercetin use resulted in a greater CPSI decrease.. Multimodal therapy using UPOINT leads to significant improvement in symptoms and quality of life. Moreover, a placebo-controlled trial for every therapy combination is not feasible, and results using UPOINT compare favorably with all large trials of monotherapy.

Topics: Adolescent; Adrenergic alpha-Antagonists; Adult; Aged; Benzhydryl Compounds; Chronic Disease; Cohort Studies; Cresols; Drug Therapy, Combination; Follow-Up Studies; Humans; Male; Middle Aged; Muscarinic Antagonists; Pain Measurement; Pelvic Pain; Phenotype; Phenylpropanolamine; Probability; Prospective Studies; Prostatitis; Quinazolines; Risk Assessment; Severity of Illness Index; Tolterodine Tartrate; Treatment Outcome; Young Adult