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European Journal of Case Reports in... 2022Phenazopyridine is an over-the-counter urinary analgesic commonly used to alleviate the burning and urgency associated with lower urinary tract infections....
INTRODUCTION
Phenazopyridine is an over-the-counter urinary analgesic commonly used to alleviate the burning and urgency associated with lower urinary tract infections. Methaemoglobinaemia is an uncommon adverse effect of phenazopyridine use. We report a case of methaemoglobinaemia in a patient prescribed daily phenazopyridine to treat urethral and bladder irritation caused by a chronic indwelling Foley catheter.
CASE DESCRIPTION
A 55-year-old female resident of a long-term acute care facility with a chronic Foley, tracheostomy and ventilator-dependent respiratory failure was observed to have generalized dusky skin and hypoxia. Pulse oximetry was reading in the high 80s despite administration of 100% FiO2. ABG revealed paO2 of 451, oxyhaemoglobin level 75% and methaemoglobin level 22%. Medication review indicated that the patient was prescribed phenazopyridine 400 mg TID for the previous 2 months. This medication was discontinued. Considering she was chronically taking mirtazapine, she can increase risk of serotonin syndrome should she be administered first-line treatment with methylene blue. Vitamin C was thus instead administered as a second-line agent. Serial ABGs showed a rapid decline in methaemoglobin levels and an increase in oxyhaemoglobin within 2 days.
DISCUSSION
Acquired methaemoglobinaemia is a rare adverse effect of treatment with phenazopyridine. This risk increases when drug dosage and duration exceed manufacturer specifications. Treatment typically includes cessation of the offending drug and administration of methylene blue in severe cases. A thorough medication reconciliation should be performed prior to methylene blue initiation, as patients taking serotonergic medications (for example, MAOIs, SSRIs, SNRIs, TCAs) are at increased risk of serotonin toxicity with co-administration of methylene blue. In these instances, ascorbic acid/vitamin C can be chosen as an alternative treatment agent.
CONCLUSION
Work-up of refractory hypoxia should involve a thorough review of medications as even some over-the-counter drugs can cause the fatal side effect of methaemoglobinaemia. Treatment with vitamin C should be considered over methylene blue if serotonergic medications have been recently prescribed in order to avoid risk of serotonin syndrome.
LEARNING POINTS
Methaemoglobinaemia is an uncommon, life-threatening adverse effect of phenazopyridine use. Presentation depends on the severity of the disorder, ranging from headache, weakness, lightheadedness and dyspnoea, to arrhythmias, confusion, seizures and multiorgan failure.Workup of refractory hypoxia should involve a comprehensive medication review as even some over-the-counter drugs can cause methaemoglobinaemia.Management of methaemoglobinaemia involves cessation of the offending drug, administration of supplemental oxygen and treatment with methylene blue (1-2 mg/kg) if MetHb >30%, or for symptomatic patients with MetHb >20%. Vitamin C can be used as an alternative agent if there is a contraindication to methylene blue (for example, with patients simultaneously receiving serotonergic medications and/or those with G6PD deficiency).
PubMed: 35265556
DOI: 10.12890/2022_003191 -
The Annals of Pharmacotherapy 1996
Review
Topics: Anesthetics, Local; Clinical Trials as Topic; Humans; Phenazopyridine; Reproducibility of Results; Urinary Tract Infections
PubMed: 8826573
DOI: 10.1177/106002809603000727 -
Cureus Jan 2023Methemoglobinemia is a condition caused by increased methemoglobin, a reduced form of hemoglobin, in the blood. This causes the molecules to bind oxygen more tightly and...
Methemoglobinemia is a condition caused by increased methemoglobin, a reduced form of hemoglobin, in the blood. This causes the molecules to bind oxygen more tightly and decreases their ability to release that oxygen to tissue. Most cases of methemoglobinemia are acquired and occur either in pediatric populations or in individuals with predisposing conditions. This report illustrates a case of an otherwise healthy 31-year-old patient presenting to the emergency department with cyanosis of the hands and mouth and an O2 saturation of 78% after taking increased doses of the over-the-counter medication phenazopyridine. A "chocolate-brown" color of her arterial blood, and increased methemoglobin levels of 20.2%, confirmed the diagnosis of methemoglobinemia. She was treated with both methylene blue and ascorbic acid, and her oxygen saturation and serum chemistry returned to normal levels within a few hours. The case highlights the importance of discussing the dosage of all over-the-counter medications with patients and recognizing the signs and symptoms of methemoglobinemia.
PubMed: 36788851
DOI: 10.7759/cureus.33715 -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Carcinogens; Carcinoma, Hepatocellular; Environmental Exposure; Female; Humans; Liver Neoplasms
PubMed: 21863079
DOI: No ID Found -
American Journal of Obstetrics and... Aug 2022The efficacy of intradetrusor onabotulinumtoxinA injections for the management of idiopathic overactive bladder has been well-established. The injections are typically... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The efficacy of intradetrusor onabotulinumtoxinA injections for the management of idiopathic overactive bladder has been well-established. The injections are typically performed in the office setting using local analgesia, most commonly a 20 to 30-minute intravesical instillation of lidocaine. There are limited data evaluating alternative bladder analgesics.
OBJECTIVE
To compare pain scores with preprocedure oral phenazopyridine vs intravesical lidocaine in women undergoing intradetrusor onabotulinumtoxinA injections for idiopathic overactive bladder.
STUDY DESIGN
Nonpregnant adult females with idiopathic overactive bladder, scheduled for office injection of 100 units of intradetrusor onabotulinumtoxinA were randomized to either 200 mg of oral phenazopyridine taken 1 to 2 hours preprocedure or a 20-minute preprocedure intravesical instillation of 50 mL of 2% lidocaine. We excluded participants with neurogenic bladders, and those who had received intradetrusor onabotulinumtoxinA injections in the previous 12 months. The primary outcome was pain measured by a 100-mm visual analog scale. Demographic characteristics and overall satisfaction with the procedure were also recorded. Providers answered questions about cystoscopic visualization, ease of procedure, and perception of participant comfort. Prespecified noninferiority margin was set to equal the anticipated minimum clinically important difference of 14 mm. A planned sample of 100 participants, 50 in each treatment arm, provided 80% power to detect noninferiority at a significance level of.05. We performed a modified intention-to-treat analysis and compared variables with the t test or the Fisher exact test.
RESULTS
A total of 111 participants were enrolled, and complete data were obtained for 100 participants; 47 participants were randomized to phenazopyridine and 53 to lidocaine. Baseline characteristics did not differ between groups. There were 19.6% and 20.8% of participants in the phenazopyridine and lidocaine groups, respectively, who previously underwent intradetrusor onabotulinumtoxinA injections. The mean postprocedure pain was 2.7 mm lower in the phenazopyridine group than in the lidocaine group (95% confidence interval, -11.3 to 10.7), demonstrating noninferiority. More than 90% of participants in both groups stated that the pain was tolerable. Slightly more participants reported being "very satisfied" in the lidocaine group, although this was not statistically significant (50.0% vs 40.4%; P=.34). Providers reported clear visualization in 89.4% of participants in the phenazopyridine group and in 100% of participants in the lidocaine group (P=.02). Provider perception of participant comfort and overall ease of procedure were not different between groups. Length of time in the exam room was significantly shorter in the phenazopyridine than in the lidocaine group (44.4 vs 57.5 minutes; P=.0003).
CONCLUSION
In women receiving intradetrusor onabotulinumtoxinA injections for idiopathic overactive bladder, oral phenazopyridine was noninferior to intravesical lidocaine for procedural pain control. Phenazopyridine is well-tolerated by participants, allows for the procedure to be performed with similar ease, and is associated with shorter appointment times.
Topics: Adult; Analgesia; Botulinum Toxins, Type A; Female; Humans; Lidocaine; Pain; Phenazopyridine; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive
PubMed: 35580634
DOI: 10.1016/j.ajog.2022.05.025 -
Renal Failure Jun 2014Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration,... (Review)
Review
Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridine-induced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage.
Topics: Aged; Humans; Male; Nephritis, Interstitial; Phenazopyridine
PubMed: 24575779
DOI: 10.3109/0886022X.2014.890054 -
Neuropsychopharmacology : Official... Nov 2022Alzheimer's disease (AD) is the most common form of dementia with no effective treatment options. A complete elucidation of its underlying molecular mechanisms,...
Alzheimer's disease (AD) is the most common form of dementia with no effective treatment options. A complete elucidation of its underlying molecular mechanisms, including the transcription regulation of genes critically involved in AD, may shed light on new therapeutic development. RPS23RG1 is a newly identified AD-associated gene, whose expression is decreased in AD and restoration can attenuate AD-like phenotypes in animal models. However, the transcription regulation of RPS23RG1 remains unknown. In this study, we explored the promoter of RPS23RG1 and identified its transcription initiation site (TSS) at 1525 bp upstream of the ATG translation start codon. Progressive deletion analysis determined the presence of a negative regulatory region and a positive regulatory region within nucleotide positions +1127 to +1187 and +732 to +1127 relative to the TSS (+1), respectively. We conducted a reporter system to screen for compounds that increase RPS23RG1 expression through antagonizing its negative regulatory elements and identified phenazopyridine. Importantly, we demonstrated that phenazopyridine not only promoted RPS23RG1/Rps23rg1 expression, but also reduced AD-like pathologies and cognitive impairments in the APP/PS1 AD model mice. We also determined a critical negative regulatory domain of RPS23RG1 within nucleotide positions +1177 to +1187 and found that the transcription factor SMAD3 bound to this domain. Inhibition of SMAD3 promoted RPS23RG1 expression. Moreover, phenazopyridine reduced SMAD3 binding to the RPS23RG1 promoter without affecting SMAD3 phosphorylation and nuclear localization. Taken together, our results determine the transcription regulation mechanism of RPS23RG1 and show that phenazopyridine has potential for AD treatment through regulating RPS23RG1 transcription.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Codon, Initiator; Disease Models, Animal; Mice; Mice, Transgenic; Nucleotides; Phenazopyridine; Phenotype; Transcription Factors
PubMed: 35821069
DOI: 10.1038/s41386-022-01373-7 -
Urologic Nursing Jun 2004
Review
Topics: Anesthetics, Local; Humans; Patient Education as Topic; Phenazopyridine; Urinary Tract Infections
PubMed: 15311491
DOI: No ID Found