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Urology Journal Sep 2020Intravesical BCG (Bacillus Calmette-Guérin) therapy is indicated as an effective treatment for patients with non-muscle-invasive bladder cancer, despite associate with... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the Efficacy of Oxybutynin, Phenazopyridine, Celecoxib, and Placebo in the Treatment of Urinary Tract Symptoms after BCG Therapy in Patients with Bladder Tumors.
PURPOSE
Intravesical BCG (Bacillus Calmette-Guérin) therapy is indicated as an effective treatment for patients with non-muscle-invasive bladder cancer, despite associate with the side effects. In this study, the incidence of BCG therapy adverse effects was compared among three groups of patients who received celecoxib, phenazopyridine, and oxybutynin with placebo.
MATERIALS AND METHODS
The randomized controlled clinical trial was conducted on four groups using the parallel group method. A checklist is used for weekly assessment of urinary symptoms, systemic symptoms of BCG therapy, and adverse drug reactions.
RESULTS
The study included 120 patients, 10 female and 110 male. The mean age 59.65 ± 6.2 years. The results of multivariate analysis show that there is a significant decrease in urinary frequency for patients who received phenazopyridine (95% CI: 0.09, 0.31, OR = 0.17, P <.001) and also celecoxib group (95% CI: 0.10, 0.43, OR = 0.21, P <.001) compared to those in placebo group. Patients in celecoxib group (95% CI: 0.02, 0.07 ,OR = 0.04, P <.001), phenazopyridine (95% CI : 0.07, 0.37,OR=0.16, P <.001) and oxybutynin (95% CI: 0.02, 0.12,OR = 0.05, P <.001) were less likely to have urgency than those in placebo. Moreover, significant decrease was found for dysuria in the three treatment groups in comparison with placebo group.
CONCLUSION
According to the results, celecoxib, phenazopyridine and oxybutynin can effectively decrease the side effects of BCG immunotherapy compared to placebo. Among these three treatments, the most effective and safest treatment option is celecoxib.
Topics: Adjuvants, Immunologic; Administration, Intravesical; Aged; BCG Vaccine; Celecoxib; Female; Humans; Male; Mandelic Acids; Middle Aged; Phenazopyridine; Urinary Bladder Neoplasms; Urinary Tract
PubMed: 32981029
DOI: 10.22037/uj.v16i7.5947 -
American Journal of Therapeutics Dec 2020Recognition of the agents most commonly implicated in causing methemoglobinemia can provide context for making therapeutic decisions and inform the diagnostic process....
BACKGROUND
Recognition of the agents most commonly implicated in causing methemoglobinemia can provide context for making therapeutic decisions and inform the diagnostic process. We evaluated the etiologic agents most commonly implicated in clinically significant methemoglobinemia using data from the National Poison Data System (NPDS).
STUDY QUESTION
What are the most frequent etiologic agents associated with clinically significant methemoglobinemia.
STUDY DESIGN
This was a retrospective cross-sectional chart review using electronic data from the NPDS. The NPDS database was queried to identify cases from July 1, 2007, to June 30, 2017, that were coded as methylene blue treatment recommended and/or performed. Cases were excluded if the substance(s) have never been known to cause methemoglobin or the substances suggested methylene blue was used adjunctively for refractory shock (eg, calcium channel or beta blocker). Multiple substance exposures were reviewed and substances not known to cause methemoglobinemia were excluded.
MEASURES AND OUTCOMES
The primary end point was to summarize the most frequent etiologic agents associated with the administration of methylene blue for clinically significant methemoglobinemia.
RESULTS
There were 2563 substances reported in 1209 cases. After excluding coingestants and cases not associated with methemoglobinemia, there were 1236 substances. The top 4 substance categories were benzocaine, phenazopyridine, dapsone, and nitrates/nitrites.
CONCLUSIONS
This study reveals the relative contribution of various drugs and chemicals associated with methylene blue administration. Over two-thirds of all cases were associated with benzocaine, phenazopyridine, dapsone, and nitrates/nitrites.
Topics: Benzocaine; Cross-Sectional Studies; Humans; Methemoglobinemia; Methylene Blue; Poisons; Retrospective Studies
PubMed: 33416248
DOI: 10.1097/MJT.0000000000001277 -
Urology Practice Jun 2024Office administration of intradetrusor onabotulinumtoxinA is commonly used to treat overactive bladder. For preprocedure analgesia, either 50 mL 2% intravesical...
INTRODUCTION
Office administration of intradetrusor onabotulinumtoxinA is commonly used to treat overactive bladder. For preprocedure analgesia, either 50 mL 2% intravesical lidocaine instillation for 20 to 30 minutes or 200 mg oral phenazopyridine can be used. Phenazopyridine is associated with shorter appointment times and is noninferior to lidocaine for pain control in this setting. We performed a cost analysis of phenazopyridine vs lidocaine for analgesia before office intradetrusor onabotulinumtoxinA injection for the treatment of idiopathic overactive bladder.
METHODS
A health care sector-perspective cost analysis was performed. The following assumptions were made: (1) similar efficacy of each medication in providing adequate analgesia, (2) similar physician ease of performing the procedure with either analgesic, and (3) similar patient satisfaction with either analgesic. Average cost of medications, adverse reactions, nursing tasks, and office visit time were found in publicly available data. Sensitivity analyses were performed using TreeAge Pro 2021, R1 software.
RESULTS
Phenazopyridine is less costly compared to lidocaine per visit for office intradetrusor onabotulinumtoxinA injection ($827 vs $925). A difference of $98 per procedure provides a total annual cost savings of over $24 million if all procedures are performed with phenazopyridine instead of lidocaine. Sensitivity analysis showed that phenazopyridine remained less costly under most circumstances, and threshold analysis provided exact circumstances under which phenazopyridine is no longer cost saving.
CONCLUSIONS
Phenazopyridine provides cost savings compared to lidocaine for analgesia before office intradetrusor onabotulinumtoxinA injection for the treatment of idiopathic overactive bladder. If adopted by providers nationwide, phenazopyridine may reduce health care spending and minimize office visit time while maintaining patient pain control and satisfaction.
PubMed: 38913587
DOI: 10.1097/UPJ.0000000000000628 -
Clinical Practice and Cases in... May 2022As ketamine gains traction as an alternative to opiates in the treatment of chronic pain, ketamine-induced ulcerative cystitis is now being recognized as a complication...
INTRODUCTION
As ketamine gains traction as an alternative to opiates in the treatment of chronic pain, ketamine-induced ulcerative cystitis is now being recognized as a complication of its use. The first-line treatment is phenazopyridine, an over-the-counter medication for dysuria that historically has been known to cause methemoglobinemia. This report details the case of a patient presenting to the emergency department (ED) with methemoglobinemia.
CASE REPORT
A 66-year-old woman with a complicated medical history presented to the ED with anemia and hypoxia after extended use of phenazopyridine for treatment of ketamine-induced ulcerative cystitis. She was found to have methemoglobinemia secondary to phenazopyridine used to treat her ketamine-induced ulcerative cystitis, a previously undocumented sequelae of chronic ketamine use. She was admitted to the hospital for three days and made a full recovery.
CONCLUSION
This case highlights the need to suspect ketamine-induced ulcerative cystitis in patients who use ketamine chronically and be judicious in the use of phenazopyridine for symptom management to prevent life-threatening complications.
PubMed: 35701344
DOI: 10.5811/cpcem.2022.1.55277 -
Urology Aug 2021To determine the true failure rate of opioid free ureteroscopy (OF-URS) and rates of new-persistent opioid use utilizing a national prescription drug monitoring program.
OBJECTIVE
To determine the true failure rate of opioid free ureteroscopy (OF-URS) and rates of new-persistent opioid use utilizing a national prescription drug monitoring program.
MATERIAL AND METHODS
We identified 239 patients utilizing our retrospective stone database who underwent OF-URS from Februrary 2018-March 2020. In Feb 2018, we initiated a OF-URS pathway (diclofenac, tamsulosin, acetaminophen, pyridium and oxybutynin). Patients who had a contraindication to NSAIDs were excluded from primary analyses. A prescription drug monitoring program was then utilized to determine the number of patients who failed OF-URS (defined as receipt of an opioid within 31 days of surgery) as well as rates of new-persistent opioid use (defined as receipt of opioid 91-180 days after surgery). All statistical analyses were performed using SAS 9.4. Tests were 2-sided and statistical significance was set at P<0.05.
RESULTS
We found a OF-URS failure rate of 16.6% and 14.0% in the total and opioid naïve cohorts, respectively. Rates of new-persistent opioid use were 0.9% and 1.2%, respectively (lower than published expected rate of ~6% after URS with postoperative opioids). 91% of patients obtained opioid from alternative sources. Uni/multivariate analyses were performed for both cohorts. In the total cohort, benzodiazepine users had a lower risk of OF-URS failure on multivariate analysis. No variables were associated with OF-URS failure in the opioid naïve cohort.
CONCLUSION
The true failure rate of OF-URS is higher than previously thought at 16.6% and 14.0%. However, efforts to reduce opioid prescriptions with OF-URS pathways have successfully reduced new-persistent opioid use.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Analgesics, Opioid; Diclofenac; Drug Prescriptions; Female; Humans; Kidney Calculi; Male; Mandelic Acids; Middle Aged; Pain, Postoperative; Phenazopyridine; Retrospective Studies; Tamsulosin; Ureteroscopy
PubMed: 33774043
DOI: 10.1016/j.urology.2021.03.011 -
Journal of Thermal Biology Oct 2022Injury to the intestinal epithelial cells and loss of the intestinal barrier are critical to heatstroke. To reveal the mechanism through which heatstroke leads to...
Injury to the intestinal epithelial cells and loss of the intestinal barrier are critical to heatstroke. To reveal the mechanism through which heatstroke leads to intestinal epithelial injury, the relationship between reactive oxygen species (ROS), c-Jun NH2-terminal kinase (JNK), and lysosomes were studied in intestinal epithelial cells subjected to heat stress. Cells of heat stress groups were incubated at 43 °C for 1 h, then incubated at 37 °C as indicated. Control group cells were incubated at 37 °C. Cell-counting kit-8 assay was used to assess cell viability. Cells were labeled with 2'-7'dichlorofluorescin diacetate and acridine orange (AO) staining, respectively, the total ROS and AO were detected by confocal laser scanning microscopy and flow cytometry. Apoptosis was analyzed by flow cytometry using annexin V-fluorescein isothiocyanate/prodium iodide staining, the expressions of mitogen-activated protein kinases were detected by western blotting. Heat stress induced apoptosis and inhibited cell viability, the production of ROS, and lysosomal injury in IEC-6 cells. After pretreatment with the lysosomal cathepsin inhibitor E64, the JNK inhibitor SP600125, or the ROS scavenger NAC, the effect of heat stress on apoptosis or lysosomal injury was significantly attenuated. In conclusion, heat stress induced apoptosis, lysosomal injury, and the accumulation of ROS in IEC-6 cells; mechanistically, this occurred through the ROS-induced activation of JNK signaling, which mediated the lysosomal injury and ultimately apoptosis.
Topics: Acridine Orange; Animals; Annexin A5; Apoptosis; Cathepsins; Epithelial Cells; Fluoresceins; Heat Stress Disorders; Heat Stroke; Heat-Shock Response; Intestinal Diseases; Iodides; Isothiocyanates; Lysosomes; Mitogen-Activated Protein Kinases; Phenazopyridine; Rats; Reactive Oxygen Species
PubMed: 36195392
DOI: 10.1016/j.jtherbio.2022.103326 -
ChemMedChem Apr 2021Rev1 is a protein scaffold of the translesion synthesis (TLS) pathway, which employs low-fidelity DNA polymerases for replication of damaged DNA. The TLS pathway helps...
Rev1 is a protein scaffold of the translesion synthesis (TLS) pathway, which employs low-fidelity DNA polymerases for replication of damaged DNA. The TLS pathway helps cancers tolerate DNA damage induced by genotoxic chemotherapy, and increases mutagenesis in tumors, thus accelerating the onset of chemoresistance. TLS inhibitors have emerged as potential adjuvant drugs to enhance the efficacy of first-line chemotherapy, with the majority of reported inhibitors targeting protein-protein interactions (PPIs) of the Rev1 C-terminal domain (Rev1-CT). We previously identified phenazopyridine (PAP) as a scaffold to disrupt Rev1-CT PPIs with Rev1-interacting regions (RIRs) of TLS polymerases. To explore the structure-activity relationships for this scaffold, we developed a protocol for co-crystallization of compounds that target the RIR binding site on Rev1-CT with a triple Rev1-CT/Rev7 /Rev3-RBM1 complex, and solved an X-ray crystal structure of Rev1-CT bound to the most potent PAP analogue. The structure revealed an unexpected binding pose of the compound and informed changes to the scaffold to improve its affinity for Rev1-CT. We synthesized eight additional PAP derivatives, with modifications to the scaffold driven by the structure, and evaluated their binding to Rev1-CT by microscale thermophoresis (MST). Several second-generation PAP derivatives showed an affinity for Rev1-CT that was improved by over an order of magnitude, thereby validating the structure-based assumptions that went into the compound design.
Topics: Dose-Response Relationship, Drug; Drug Design; Enzyme Inhibitors; Humans; Molecular Structure; Nucleotidyltransferases; Phenazopyridine; Structure-Activity Relationship
PubMed: 33314657
DOI: 10.1002/cmdc.202000893 -
Clinics and Practice Oct 2022Methemoglobinemia is a rare blood disorder characterized by the oxidation of heme iron from ferrous (Fe) to ferric (Fe) state, which increases oxygen affinity and...
Methemoglobinemia is a rare blood disorder characterized by the oxidation of heme iron from ferrous (Fe) to ferric (Fe) state, which increases oxygen affinity and impairs oxygen release to the tissue causing hypoxia. It can be congenital or acquired; however, most cases are acquired and caused by exogenous substances such as medications, chemicals, and environmental substances. Phenazopyridine is an over-the-counter urinary analgesic medication commonly used for symptomatic relief of dysuria and has been reported to cause methemoglobinemia. However, only a handful of cases of phenazopyridine-induced methemoglobinemia have been reported. We present a case of an 89-year-old female who presented with severe hypoxia, shortness of breath, headache, nausea, and dizziness caused by phenazopyridine-induced methemoglobinemia. She was found to have a methemoglobin level of 21.5% and was treated with methylene blue, leading to a rapid improvement of her symptoms. She was taking one over-the-counter phenazopyridine 200 mg tablet three times daily for two weeks for her chronic dysuria. This case highlights the need to have a high index of suspicion of phenazopyridine-induced methemoglobinemia in a patient presenting with unexplained shortness of breath with a history of phenazopyridine use as it could lead to severe methemoglobinemia with hypoxia that could potentially be fatal if not promptly diagnosed.
PubMed: 36412668
DOI: 10.3390/clinpract12060089 -
The Journal of Urology Apr 2023Post-ureteroscopy stent placement carries significant morbidity which can interfere with daily life. This discomfort unfortunately leads to high utilization of opioid... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Post-ureteroscopy stent placement carries significant morbidity which can interfere with daily life. This discomfort unfortunately leads to high utilization of opioid pain medications, which have a known risk of addiction. Cannabidiol oil represents an alternative analgesic that has proven anti-inflammatory and antinociceptive effects. The purpose was to evaluate the effect of a Food and Drug Administration-approved cannabidiol oil (Epidiolex) on pain control and opioid usage in the post-ureteroscopy setting.
MATERIALS AND METHODS
This was a prospective, randomized, double-blind, placebo-controlled trial at a tertiary care center. Ninety patients undergoing ureteroscopy with stent placement for urinary stone disease were randomized 1:1 to placebo or 20 mg cannabidiol oil daily for 3 days postoperatively. Both groups were prescribed a rescue narcotic, tamsulosin, oxybutynin, and phenazopyridine. Daily pain scores, medication usage, and ureteral stent symptoms using the validated Ureteral Stent Symptom Questionnaire were recorded postoperatively.
RESULTS
Both the placebo and cannabidiol oil groups were not different in pre- and perioperative characteristics. There was no difference in pain scores or opioid usage between groups postoperatively. The level of discomfort with ureteral stents was also not different between groups when comparing physical activity, sleep, urination, and activities of daily life.
CONCLUSIONS
This randomized, blinded, placebo-controlled trial showed that cannabidiol oil is safe but ineffective when compared to placebo in reducing post-ureteroscopic stent discomfort or opioid usage. Despite the availability of numerous analgesic agents, stent symptoms continue to be a dissatisfier for most patients, suggesting additional work needs to focus on novel interventions and pain control.
Topics: Humans; Ureteroscopy; Cannabidiol; Analgesics, Opioid; Prospective Studies; Urinary Calculi; Pain; Stents; Ureteral Calculi
PubMed: 36891837
DOI: 10.1097/JU.0000000000003139 -
Asia Pacific Allergy Jan 2022Delayed hypersensitivity reaction of penicillin is commonly seen, but never reported in pyridium. This case illustrates a patient with delayed hypersensitivity reaction...
Delayed hypersensitivity reaction of penicillin is commonly seen, but never reported in pyridium. This case illustrates a patient with delayed hypersensitivity reaction after the use of augmentin and pyridium. Skin patch test, surprisingly, confirmed pyridium delayed hypersensitivity.
PubMed: 35174061
DOI: 10.5415/apallergy.2022.12.e10