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WMJ : Official Publication of the State... Sep 2023Trimethoprim-sulfamethoxazole (TMP-SMX) and phenazopyridine are individually associated with methemoglobinemia through a series of altered reduction-oxidation reactions....
A Case That Will Take Your Breath Away: Acquired Methemoglobinemia Related to Trimethoprim-Sulfamethoxazole and Phenazopyridine Ingestion for Treatment of Urinary Tract Infection.
Trimethoprim-sulfamethoxazole (TMP-SMX) and phenazopyridine are individually associated with methemoglobinemia through a series of altered reduction-oxidation reactions. We report a case of methemoglobinemia associated with concurrent use of TMP/SMX and phenazopyridine in a 70-year-old woman with recurrent urinary tract infections. She presented to the emergency department for worsening back pain in the setting of recurrent urinary tract infections, concerning for pyelonephritis. During her workup, she became acutely hypoxic. The emergency department provider suspected the presence of abnormal hemoglobin. An arterial blood gas showing elevated levels of methemoglobinemia confirmed the suspicion. The combined use of TMP/SMX and phenazopyridine was thought to be the likely etiology of hypoxia. This case highlights the importance of medication management in the geriatric population, as well as the judicious use of antibiotics for urinary tract infections-a common chief complaint in the primary care setting.
Topics: Aged; Female; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Phenazopyridine; Methemoglobinemia; Urinary Tract Infections; Eating
PubMed: 37768772
DOI: No ID Found -
Environmental Science and Pollution... Oct 2023Pharmaceutical wastewater treatment is an essential component of environmental protection and sustainable development. In this study, our aim was to investigate the...
Pharmaceutical wastewater treatment is an essential component of environmental protection and sustainable development. In this study, our aim was to investigate the morphology, characterization, and effectiveness of TiO/graphene composite nanofiber photocatalysts in the treatment of pharmaceutical wastewater containing three different pharmaceutical groups, such as an antibiotic (rifampin), painkiller (phenazopyridine), and immunosuppressant (azathioprine). Various parameters such as pH, salt concentration, and initial pharmaceutical compound concentration were optimized to achieve maximum degradation kinetics and efficiency. The optimum conditions were determined to be 1.5% graphene content, 30 ppm initial concentration of pharmaceutical compound, pH=5, and a 0.5 g/L photocatalyst dose. The presence of salt slightly decreased the degradation kinetics, but it did not significantly affect the performance of the TiO/graphene composite nanofibers photocatalyst. At optimum condition, TiO/1.5% graphene composite nanofibers degraded 50% of phenazopyridine, 86.89% of rifampin, and completely azathioprine. Comparing with phenazopyridine, N heteroatom-rich molecule of azathioprine and hydroxyl-rich molecule of rifampin lead to being susceptible to photocatalytic degradation. The reuse of the photocatalyst in multiple cycles showed consistent performance, indicating its potential for practical and economic applications.
Topics: Phenazopyridine; Nanofibers; Azathioprine; Graphite; Rifampin; Titanium; Pharmaceutical Preparations; Catalysis
PubMed: 37747607
DOI: 10.1007/s11356-023-29869-9 -
Cureus Jun 2023Sulfhemoglobin is formed by the irreversible bonding of sulfur atoms to the heme molecule. Oxygen is then unable to bind the heme molecule, rendering the hemoglobin...
Sulfhemoglobin is formed by the irreversible bonding of sulfur atoms to the heme molecule. Oxygen is then unable to bind the heme molecule, rendering the hemoglobin molecule unable to carry oxygen. The most common etiology of sulfhemoglobinemia is the use/misuse of sulfur-containing medications such as AZO. Unlike methemoglobin, sulfhemoglobin, due to its irreversible binding, has no antidote, and the treatment is ultimately supportive. We present a case of a 53-year-old female who presented to the emergency room endorsing dysuria and was noted to have abnormally low oxygen saturation (SpO2) despite having high arterial oxygen pressure (PaO2) on blood gas. History was significant for dysuria developed while traveling and the use of over-the-counter AZO four times daily for the past 10 days. She was diagnosed with a presumed dyshemoglobinemia and, upon return of send-out labs, was confirmed to have sulfhemoglobinemia attributed to phenazopyridine. This case highlights the importance of the recognition of potential dyshemoglobinemias and consideration of sulfhemoglobinemia as a potential causative etiology, especially in patients taking sulfur-containing medications.
PubMed: 37496545
DOI: 10.7759/cureus.40944 -
Food and Chemical Toxicology : An... Aug 2023Azo compounds are widely distributed synthetic chemicals in the modern world. Their most important applications are as dyes, but, in addition, several azo compounds are... (Review)
Review
Azo compounds are widely distributed synthetic chemicals in the modern world. Their most important applications are as dyes, but, in addition, several azo compounds are used as pharmaceuticals. Ingested azo compounds can be reduced by the action of bacteria in the gut, where the oxygen tension is low, and the development of microbiome science has allowed more precise delineation of the roles of specific bacteria in these processes. Reduction of the azo bond of an azo compound generates two distinct classes of aromatic amine metabolites: the starting material that was used in the synthesis of the azo compound and a product which is formed de novo by metabolism. Reductive metabolism of azo compounds can have toxic consequences, because many aromatic amines are toxic/genotoxic. In this review, we discuss aspects of the development and application of azo compounds in industry and medicine. Current understanding of the toxicology of azo compounds and their metabolites is illustrated with four specific examples - Disperse Dyes used for dyeing textiles; the drugs phenazopyridine and eltrombopag; and the ubiquitous food dye, tartrazine - and knowledge gaps are identified. SUBMISSION TO: FCT VSI: Toxicology of Dyes.
Topics: Azo Compounds; Coloring Agents; Tartrazine; Bacteria; Amines
PubMed: 37451600
DOI: 10.1016/j.fct.2023.113932 -
Hematology Reports May 2023Methemoglobinemia is an acute medical emergency that requires prompt correction. Physicians should have a high degree of suspicion of methemoglobinemia in cases that...
Phenazopyridine-Induced Methemoglobinemia in a Jehovah's Witness Treated with High-Dose Ascorbic Acid Due to Methylene Blue Contradictions: A Case Report and Review of the Literature.
Methemoglobinemia is an acute medical emergency that requires prompt correction. Physicians should have a high degree of suspicion of methemoglobinemia in cases that present with hypoxemia that does not resolve with supplemental oxygenation, and they should confirm this suspicion with a positive methemoglobin concentration on arterial blood gas. There are multiple medications that can induce methemoglobinemia, such as local anesthetics, antimalarials, and dapsone. Phenazopyridine is an azo dye used over-the-counter as a urinary analgesic for women with urinary tract infections, and it has also been implicated in causing methemoglobinemia. The preferred treatment of methemoglobinemia is methylene blue, but its use is contraindicated for patients with glucose-6-phosphatase deficiency or those who take serotonergic drugs. Alternative treatments include high-dose ascorbic acid, exchange transfusion therapy, and hyperbaric oxygenation. The authors report a case of a 39-year-old female who took phenazopyridine for 2 weeks to treat dysuria from a urinary tract infection and subsequently developed methemoglobinemia. The patient had contraindications for the use of methylene blue and was therefore treated with high-dose ascorbic acid. The authors hope that this interesting case promotes further research into the utilization of high-dose ascorbic acid for managing methemoglobinemia in patients who are unable to receive methylene blue.
PubMed: 37367083
DOI: 10.3390/hematolrep15020034 -
Gene Jul 2023Patients with chronic kidney disease (CKD) suffered from vascular calcification (VC), one major contributor for their increased mortality rate. Hedgehog (Hh) signaling...
BACKGROUND
Patients with chronic kidney disease (CKD) suffered from vascular calcification (VC), one major contributor for their increased mortality rate. Hedgehog (Hh) signaling plays a crucial role in physiological bone mineralization and is associated with several cardiovascular diseases. However, the molecular changes underlying VC is ill defined and it remains unclear whether Hh signaling intervention affects VC.
METHODS
We constructed human primary vascular smooth muscle cell (VSMC) calcification model and performed RNA sequencing. Alizarin red staining and calcium content assay were conducted to identify the occurrence of VC. Three different R packages were applied to determine differentially expressed genes (DEGs). Enrichment analysis and protein-protein interaction (PPI) network analysis were carried out to explore the biological roles of DEGs. qRT-PCR assay was then applied to validate the expression of key genes. By using Connectivity Map (CMAP) analysis, several small molecular drugs targeting these key genes were obtained, including SAG (Hedgehog signaling activator) and cyclopamine (CPN) (Hedgehog signaling inhibitor), which were subsequently used to treat VSMC.
RESULTS
Obvious Alizarin red staining and increased calcium content identified the occurrence of VC. By integrating results from three R packages, we totally obtained 166 DEGs (86 up-regulated and 80 down-regulated), which were significantly enriched in ossification, osteoblast differentiation, and Hh signaling. PPI network analysis identified 10 key genes and CMAP analysis predicted several small molecular drugs targeting these key genes including chlorphenamine, isoeugenol, CPN and phenazopyridine. Notably, our in vitro experiment showed that SAG markedly alleviated VSMC calcification, whereas CPN significantly exacerbated VC.
CONCLUSIONS
Our research provided deeper insight to the pathogenesis of VC and indicated that targeting Hh signaling pathway may represent a potential and effective therapy for VC.
Topics: Humans; Hedgehog Proteins; Calcium; Vascular Calcification; Signal Transduction; Myocytes, Smooth Muscle
PubMed: 37141952
DOI: 10.1016/j.gene.2023.147457 -
Molecular Pharmaceutics Apr 2023The purpose of the present study was to evaluate whether the population balance model (PBM) could be a suitable model for the precipitation of weak base and zwitterionic...
The purpose of the present study was to evaluate whether the population balance model (PBM) could be a suitable model for the precipitation of weak base and zwitterionic drugs in the gastrointestinal pH environment. Five poorly soluble drugs were used as model drugs (dipyridamole, haloperidol, papaverine, phenazopyridine, and tosufloxacin). PBM consists of the equations for primary nucleation, secondary nucleation, and particle growth. Each equation has two empirical parameters. The pH shift (pH-dumping) precipitation test (pH 3.0 to 6.5) was used to determine the model parameters for each drug. It was difficult to determine all six parameters by simultaneously fitting them to the precipitation profiles. Therefore, the number of model parameters was reduced from six to three by neglecting the secondary nucleation process and applying a common exponent number for the particle growth equation. Despite reducing the parameter number, PBM appropriately described the precipitation profiles in the pH shift tests. The constructed PBM model was then used to predict the precipitation profiles in an artificial stomach-intestine transfer (ASIT) test. PBM appropriately predicted the precipitation profiles in the ASIT test. These results suggested that PBM can be a suitable model to represent the precipitation of weak base and zwitterionic drugs in the gastrointestinal pH environment for biopharmaceutics modeling and simulation.
Topics: Solubility; Administration, Oral; Gastrointestinal Tract; Stomach; Computer Simulation; Hydrogen-Ion Concentration; Models, Biological; Chemical Precipitation; Intestinal Absorption
PubMed: 36929729
DOI: 10.1021/acs.molpharmaceut.3c00088 -
Clinical Case Reports Mar 2023Hemorrhagic cystitis is a common complication following the use of cyclophosphamide. Associated dysuria can be painful and there are few good options to relieve pain....
Hemorrhagic cystitis is a common complication following the use of cyclophosphamide. Associated dysuria can be painful and there are few good options to relieve pain. Phenazopyridine has historically been utilized for dysuria and is available over the counter. However, it is associated with hematologic side effects with prolonged use. Here we present a case of a patient who developed Heinz body hemolysis following prolonged administration of phenazopyridine to treat cyclophosphamide-induced hemorrhagic cystitis following hematopoietic stem cell transplant.
PubMed: 36911643
DOI: 10.1002/ccr3.7012 -
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 -
Journal of Community Hospital Internal... 2023Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic disorder which commonly affects males. It is due to a defect in the red blood cell...
Syncope Following Treatment of UTI: A Case of Acute Hemolytic Anemia, Methemoglobinemia and Acute Renal Dysfunction Following Phenazopyridine Use in a Patient With G6PD Deficiency.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic disorder which commonly affects males. It is due to a defect in the red blood cell enzyme, G6PD. Lack of G6PD makes the RBCs vulnerable to oxidant stress resulting in hemolysis. The severity of hemolytic anemia varies among individuals with G6PD deficiency. Here we present a case of an 80-year-old man admitted with syncope and jaundice. He was treated with phenazopyridine for a UTI 2 weeks ago. Subsequent investigation revealed G6PD deficiency as well as methemoglobinemia. Historically, phenazopyridine has been associated with causing methemoglobinemia and triggering hemolysis in G6PD deficient individuals. However, only a few cases have been reported in the last 60 years, making it a very rare occurrence.
PubMed: 36817304
DOI: 10.55729/2000-9666.1144