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Urology May 2018To identify difficult to see ureteral orifices (UOs), urologists need a method to stain the urine. Phenazopyridine, a urinary analgesic which discolors the urine orange,...
OBJECTIVE
To identify difficult to see ureteral orifices (UOs), urologists need a method to stain the urine. Phenazopyridine, a urinary analgesic which discolors the urine orange, can be administered orally preoperatively. We evaluated the usefulness of phenazopyridine in identifying the UOs and optimal timing of administration.
METHODS
Adult patients undergoing endoscopic procedures at the Stratton VA were prospectively enrolled. Preoperative metabolic panels were reviewed. Exclusion criteria were renal insufficiency (creatinine clearance <50 mL/min), severe hepatitis or severe liver disease, glucose-6-phosphate dehydrogenase deficiency, previous hypersensitivity to phenazopyridine, or pregnancy. In phase 1, patients undergoing office flexible cystoscopy were administered 200 mg phenazopyridine the morning of the procedure. Because of the robust orange color of the urine, phase 2 was implemented. In phase 2, patients undergoing rigid cystoscopy in the operating room took 200 mg phenazopyridine at 7 PM the night before surgery. Upon entry into the bladder, UOs were identified and urine color was graded (0 = no dye, 1 = weak, 2 = moderate, and 3 = strong). Patients were assessed postoperatively for side effects.
RESULTS
Five patients were included in phase 1. The mean time from medication to cystoscopy was 153 minutes (range 17-304 minutes). One-third of patients had excretion of grade 3 orange urine that obscured inspection of the bladder mucosa. The study design was adjusted and we transitioned to phase 2. Twenty-three patients were enrolled in phase 2. The mean time from phenazopyridine dose to cystoscopy was 14 hours (range 13-17 hours). Seventy-three percent of patients had grade 2 efflux from the UOs.
CONCLUSION
Phenazopyridine can successfully identify UOs and can be administered as early as the evening before the procedure.
Topics: Aged; Aged, 80 and over; Color; Cystoscopy; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Phenazopyridine; Ureter; Urine
PubMed: 29501712
DOI: 10.1016/j.urology.2018.02.023 -
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 -
Journal of Environmental Management Jan 2020In the present study, the potential of Azolla filiculoides (A. filiculoides) was first investigated for degradation of Phenazopyridine (PhP), an analgesic drug. The...
In the present study, the potential of Azolla filiculoides (A. filiculoides) was first investigated for degradation of Phenazopyridine (PhP), an analgesic drug. The effects of main variables such as initial pharmaceutical concentration, amount of plant, and pH were studied on the efficiency of the biological process. It was observed that A. filiculoides was able to remove pharmaceuticals from contaminated water up to 85.90% during 48 h. Then, the electro-Fenton (EF) method was applied for further removal of PhP yielding a removal rate of about 98.72% under optimum conditions during 2 h. The effects of variables including the current, amount of catalyst, and pH were also studied in this phase. Also, the probability of adsorption was investigated during this step. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis were performed for the used magnetite nanoparticles, total organic carbon (TOC) were performed to investigate PhP removal efficiency during the reaction time and Gas chromatography-mass spectrometry (GC-MS) were performed to analyze degradation byproducts of PhP. Based on the results, it was found that a combination of these bioremediation and electrochemical removal steps were capable of PhP removal from contaminated water. Therefore, this approach may be effective for phytoremediation of pharmaceutical-contaminated aquatic ecosystems.
Topics: Ecosystem; Hydrogen Peroxide; Iron; Oxidation-Reduction; Phenazopyridine; Wastewater; Water Pollutants, Chemical
PubMed: 31731027
DOI: 10.1016/j.jenvman.2019.109802 -
American Journal of Obstetrics and... Nov 2017Many gynecologic, urologic, and pelvic reconstructive surgeries require accurate intraoperative evaluation of ureteral patency. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Many gynecologic, urologic, and pelvic reconstructive surgeries require accurate intraoperative evaluation of ureteral patency.
OBJECTIVE
We performed a randomized controlled trial to compare surgeon satisfaction with 4 methods of evaluating ureteral patency during cystoscopy at the time of benign gynecologic or pelvic reconstructive surgery: oral phenazopyridine, intravenous sodium fluorescein, mannitol bladder distention, and normal saline bladder distention.
STUDY DESIGN
We conducted an unblinded randomized controlled trial of the method used to evaluate ureteral patency during cystoscopy at time of benign gynecologic or pelvic reconstructive surgery. Subjects were randomized to receive 200 mg oral phenazopyridine, 25 mg intravenous sodium fluorescein, mannitol bladder distention, or normal saline bladder distention during cystoscopy. The primary outcome was surgeon satisfaction with the method, assessed via a 100-mm visual analog scale with 0 indicating strong agreement and 100 indicating strong disagreement with the statement. Secondary outcomes included comparing visual analog scale responses about ease of each method and visualization of ureteral jets, bladder mucosa and urethra, and operative information, including time to surgeon confidence in the ureteral jets. Adverse events were evaluated for at least 6 weeks after the surgical procedure, and through the end of the study. All statistical analyses were based on the intent-to-treat principle, and comparisons were 2-tailed.
RESULTS
In all, 130 subjects were randomized to phenazopyridine (n = 33), sodium fluorescein (n = 32), mannitol (n = 32), or normal saline (n = 33). At randomization, patient characteristics were similar across groups. With regard to the primary outcome, mannitol was the method that physicians found most satisfactory on a visual analog scale. The median (range) scores for physicians assessing ureteral patency were 48 (0-83), 20 (0-82), 0 (0-44), and 23 (3-96) mm for phenazopyridine, sodium fluorescein, mannitol, and normal saline, respectively (P < .001). Surgery length, cystoscopy length, and time to surgeon confidence in visualization of ureteral jets were not different across the 4 randomized groups. During the 189-day follow-up, no differences in adverse events were seen among the groups, including urinary tract infections.
CONCLUSION
The use of mannitol during cystoscopy to assess ureteral patency provided surgeons with the most overall satisfaction, ease of use, and superior visualization without affecting surgery or cystoscopy times. There were no differences in adverse events, including incidence of urinary tract infections.
Topics: Administration, Intravenous; Administration, Oral; Adult; Coloring Agents; Contrast Media; Cystoscopy; Female; Fluorescein; Gynecologic Surgical Procedures; Humans; Hysterectomy; Indigo Carmine; Leiomyoma; Mannitol; Middle Aged; Phenazopyridine; Postoperative Complications; Plastic Surgery Procedures; Sodium Chloride; Ureter; Urinary Incontinence; Urologic Surgical Procedures; Uterine Hemorrhage; Uterine Neoplasms; Uterine Prolapse
PubMed: 28729014
DOI: 10.1016/j.ajog.2017.07.012 -
International Urogynecology Journal Dec 2023Dysuria is a common symptom present in several urological and gynecological conditions. Management relies on the underlying disease but may require additional... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION AND HYPOTHESIS
Dysuria is a common symptom present in several urological and gynecological conditions. Management relies on the underlying disease but may require additional symptomatic treatment. This study evaluated the combination of methenamine 250 mg and methylthioninium chloride 20 mg in the treatment of dysuria versus phenazopyridine.
METHODS
This was a multicenter, single-blind, randomized, superiority clinical trial, including individuals over 18 with dysuria and a score ≥ 5 points on the pre-treatment categorical scale for pain. The primary outcome was the proportion of participants presenting excellent clinical response within 24 h after treatment. Improvement up to 72 h, time to reach improvement, sustained healing, investigators' opinion, and safety were also evaluated.
RESULTS
Three hundred and fifteen participants were evaluated. Demographic characteristics and symptoms of dysuria were comparable between groups at baseline. The difference in the excellent response rate between treatments within 24 h was 12.7% (95% CI 6.16, 19.21) for pain, 9.4% (95% CI 3.32, 15.39) for burning, and 12.7% (95% CI 6.37, 18.99) for burning on urination, all in favor of the test drug, which was also superior from 36 to 48 h. Treatments were similar concerning time to reach the absence of symptoms and in the percentage of participants with sustained healing after 72 h.
CONCLUSIONS
The association of methenamine with methylthioninium is superior to phenazopyridine in the treatment of dysuria.
Topics: Humans; Dysuria; Methenamine; Methylene Blue; Pain; Phenazopyridine; Single-Blind Method; Adult
PubMed: 37851092
DOI: 10.1007/s00192-023-05669-0