This article presents a clinical case demonstrating the feasibility of using a combination of diclofenac and orphenadrine for adequate pain relief in a multimodal analgesia regimen in the early postoperative period. It also provides an overview of pain relief options used after major orthopedic and trauma surgeries in both domestic and international routine clinical practice. A unique local postoperative pain management protocol, developed taking into account the authors' capabilities and preferences, is proposed.

Ischemic stroke is a leading cause of mortality and disability globally, with limited therapeutic options. This study hypothesized that orphenadrine, an NMDA antagonist with neuroprotective, anti-inflammatory and analgesic properties would attenuate reperfusion brain injury in a rat middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia. Male rats underwent 90-min MCAO followed by reperfusion, then received orphenadrine intraperitoneally (10 and 30 mg/kg) immediately 1 h post-reperfusion and daily for 21 days. Primary outcomes included neurological deficit scores, beam walk latency, locomotor activity, infarct volume, oxidative stress (MDA, glutathione, catalase), cytokines (IL-6, TNF-α), blood-brain barrier (BBB) integrity, and expression of HIF-1α, TFAM (mitochondrial functions), caspase-3, iNOS, and Nrf-2/HO-1. Orphenadrine administration significantly improved neurological functions, muscle strength, and locomotor activity (days 1, 7, 14 and 21), reduced infarct volume, lowered MDA and nitrite, while increased antioxidants (glutathione and catalase), and decreased neuroinflammation by lowering IL-6 and TNF-α levels. It preserved BBB integrity, enhanced mitochondrial genes, hypoxia-inducing factor 1 alpha (HIF-1α) and Transcription factor A, mitochondrial (TFAM), suppressed caspase-3 and enhanced nitric oxide synthase gene expression, and nuclear factor erythroid 2-related factor 2/ Heme oxygenase-1 (Nrf-2/HO-1) expression. These findings highlight Orphenadrine as a promising multi-target neuroprotective agent via antioxidative, anti-inflammatory, and mitochondrial preservation mechanisms in ischemic stroke, warranting further investigation for clinical translation.

Chronic pain is a common and disabling feature of mast cell activation syndrome (MCAS), with no established treatment paradigm. Cannabidiol (CBD) has recently shown potential to suppress mast cell activation and degranulation. We present a unique case in which widespread, severe, refractory MCAS-related pain was treated with a combination of orphenadrine and CBD oil. Marked improvements were observed at 4 and 20 weeks posttreatment, with pain severity and interference scores reduced by 56% and 87%, respectively. This therapeutic combination may represent a promising new adjuvant approach for managing pain in MCAS and warrants further investigation. .

BACKGROUND: The evaluation of pain and medication compliance in patients with type 2 diabetes mellitus is essential for efficient illness management. This study aimed to assess the associations of medication adherence and glycemic control with pain severity among patients with diabetes mellitus. METHODS: This study was conducted with a cross-sectional design. The study used the Arabic versions of the Brief Pain Inventory Scale and the Medication Adherence Rating Scale. The patients were included from different healthcare centers in Nablus city. The data were collected via a structured questionnaire. RESULTS: In this study, 377 patients were included. Of those, 244 (64.7%) were female. The median age of the patients was 62 [IQR: 55.5, 68.0] years. The median time since the diagnosis of type 2 diabetes mellitus was 8 [IQR: 4.0, 15.0] years, and the HbA1c level was 7.8% [IQR: 6.8%, 9.0%]. Among the patients, 162 (43.0%) had no pain, 92 (24.4%) had mild pain, 43 (11.4%) had moderate pain, and 80 (21.2%) had severe pain. The median adherence score was 8.0 [7.0, 9.0]. In the multivariable analysis, pain severity was significantly associated with factors such as not having a formal education (B = − 0.21, p = 0.007), ankle pain (B = -1.01, p < 0.001), orphenadrine use (B = − 2.08, p = 0.005) and higher pain interference scores (B = 0.45, p < 0.001). For medication adherence, significant predictors included older age (B = 0.01, p = 0.038), the use of glimepiride (B = − 0.34, p = 0.009), and the use of duloxetine (B = 1.21, p = 0.022). No significant association was found between medication adherence and pain severity (p = 0.617). CONCLUSIONS: Pain severity was most strongly associated with pain interference, educational level, ankle pain, and the use of orphenadrine. Medication adherence was significantly predicted by older age, the use of glimepiride, and the use of duloxetine. These findings highlight key factors influencing pain and adherence among patients with diabetes mellitus.

SyrSpend® SF PH4 is a preservative-light, starch-based oral suspending vehicle formulated for personalized medicine in vulnerable populations such as pediatric and geriatric patients. This study evaluated the physicochemical and microbiological stability of eleven active pharmaceutical ingredients (APIs) compounded in SyrSpend® SF PH4 (liquid and dry forms). The following formulations were tested: azithromycin (40.0 mg/mL), bismuth subsalicylate (17.5 mg/mL), budesonide (0.25 mg/mL), buspirone (2.5 mg/mL), cephalexin (50.0 mg/mL), chlorpromazine hydrochloride (100.0 mg/mL), citalopram hydrobromide (2.0 mg/mL), cyanocobalamin (0.2 mg/mL), famotidine (8.0 mg/mL), meloxicam (0.2 mg/mL), and orphenadrine citrate (5.0 mg/mL). Each formulation was stored under refrigerated (2-8°C) and room temperature (20-25°C) conditions, then evaluated over 90 days using validated ultra-high-performance liquid chromatography (UHPLC) and antimicrobial effectiveness testing (AET) per USP <51>. Azithromycin was not stable at room temperature but maintained stability for 60 days under refrigeration; bismuth subsalicylate remained stable for 14 days under both storage conditions; cephalexin remained stable for 14 days at room temperature and 30 days refrigerated; budesonide, buspirone, chlorpromazine hydrochloride, citalopram hydrobromide, cyanocobalamin, famotidine, meloxicam, and orphenadrine citrate all demonstrated stability for 90 days under both conditions. AET confirmed microbial control throughout the storage period for all samples. These results confirm that SyrSpend® SF PH4 is a reliable vehicle for extemporaneous compounding of a broad range of oral liquid formulations, offering extended BUDs for most APIs tested. Its excipient profile - free from harmful substances like alcohol, parabens, propylene glycol, and sorbitol - supports safe use in pediatric and geriatric patients. The study provides evidence-based guidance for pharmacists in assigning appropriate BUDs and optimizing personalized therapy through compounded oral suspensions.

Despite the substantial amount of research on the presence of pharmaceuticals and illicit drugs (PhIDs) in freshwater environments, there is a paucity of data on these contaminants in estuarine systems, particularly in South America. Industries, the biggest port in the Southern Hemisphere, and substantial urban areas surround the Santos-São Vicente Estuarine System (SSVES), located in a Brazilian subtropical area. This study constitutes the first assessment of contamination by PhIDs in this estuarine area. Samples of superficial water, sediments, and oysters were analyzed through liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, the potential ecological risk to aquatic non-target organisms (i.e., primary producers, primary and secondary consumers) was assessed using the maximum measured environmental concentrations (MEC) of the PhIDs identified in this study. The results revealed the widespread presence of caffeine (MEC = 72.1 ng·L[-1]) > losartan (29.6 ng·L[-1]) > orphenadrine (25.9 ng·L[-1]) > benzoylecgonine (18.6 ng/L-1) > carbamazepine (7.4 ng·L[-1]) and cocaine (3.6 ng·L[-1]). These findings were obtained from relevant sites at SSVES, near areas with mangroves and anthropogenic activities, such as fishing and swimming. Consequently, the ecological risk assessment indicated significant environmental concern, as our results suggested low to moderate risks of all compounds to algae, crustaceans, and/or fish. Considering the One Health approach, further studies are recommended to investigate the potential human health risks associated with consuming contaminated seafood. Concomitantly, there is an urgent need for improvements in public sanitation, public health care for illicit drug users, and public safety actions against traffic.

A UV-chemometric approach has been developed to analyze a ternary combination of aspirin, caffeine, and orphenadrine citrate without the need for previous separation. The method is easy, specific, accurate, and highly precise. The three medications were evaluated simultaneously utilizing CLS, PLS, and PCR, which were generated based on separate data sets that yielded superior findings. Regrettably, their accurate estimation could only be achieved using the PLS approach. In order to determine the prediction power of each chemometric approach, its validity has been tested using 8 synthetic mixes. The latent variable number varies across various models as the dataset changes. The comparison of various methodologies and the assessment of the predictive capacity of each set of data were done using the predicted residual error sum of squares (PRESS) and the root mean square error of prediction (RMSEP). The created approach was also used to statistically compare the performance of PLS in a dataset with zero absorption, as well as to compare the performance of the offered chemometric methods in various datasets. The environmental impact of the created approach was assessed to determine the overall ecological sustainability of the designed methodology. According to the new Blue Applicability Grade Index (BAGI) evaluation methodology, the suggested technique was also found to be practicable.

Research on the occurrence and seasonal monitoring of pharmaceutically active compounds (PhACs) in estuarine and coastal waters has intensified recently. However, few studies have been conducted with PhACs flowing into the marine waters of South America (such as Brazil). Against this backdrop, the aims of this study were: (i) evaluate, for the first time, the seasonal occurrence throughout a year and the potential ecological risks of ten selected PhACs in marine bathing waters from Santos Bay, São Paulo, Brazil (a tropical low-wave energy semi-closed bay); and (ii) develop a list of high-priority PhACs for the monitoring based on "occurrence, persistence, bioaccumulation, and toxicity" criteria (OPBT). Four water sampling campaigns were carried out throughout the four seasons of the year. The results showed that: (i) ten PhACs (namely, caffeine/CAF (87.20-567.23 ng/L); carbamazepine/CAR [below the limit of quantification (<LOQ) to 3.42 ng/L]; citalopram/CIT (<LOQ to 2.98 ng/L); acetaminophen/ACE (<LOQ to 4.00 ng/L); diclofenac/DIC (<LOQ to 5.17 ng/L); orphenadrine/ORP (<LOQ to 3.92 ng/L); atenolol/ATE (<LOQ to 2.98 ng/L); losartan/LOS (<LOQ to 3.98 ng/L); enalapril/ENA (<LOQ to 2.23 ng/L); and furosemide/FUR (<LOQ to 3.24 ng/L), were found in Santos Bay; (ii) the "mass gathering" in Santos city during New Year holiday contributed significantly to increase the mass load of nine PhACs in marine waters; (iii) the ecological risk assessment revealed great environmental concern for the aquatic ecosystem, since the results suggest low to moderate risks of CAF, followed by LOS > ACE > DIC and CAR to algae, crustaceans, and fishes; (iv) Finally, regarding the OPBT ranking, the DIC was the highest-priority PhAC in Santos Bay, followed by: ORP > LOS > CIT > CAR > FUR > ATE > CAF > ACE > ENA.

Hospitalized post-operative cardiovascular disease (CVD) patients are often subject to polypharmacy, increasing the risk of potential drug-drug interactions (pDDIs). This observational study assessed 384 post-operative CVD patients for pDDIs using Micromedex Drug-Int® and Lexicomp Interact®. Prevalence, severity, onset and documentation of pDDIs were analyzed using SPSS 23.0, with logistic regression identifying factors associated with at least two major pDDIs or two pDDIs categorized as X, D, or C. Micromedex Drug-Int® revealed a median of 6.23 pDDIs per patient, with 98.7% of patients having ≥1 pDDIs. Of 2,389 pDDIs, 64.1% were major. Lexicomp Interact® data showed a median of 7.15 pDDIs per patient, with 99.2% of patients having ≥1 pDDIs. Class C interactions were the most frequent (62.1%), followed by Classes B, D and X. Additionally, the study identified unique pDDIs from Lexicomp, including Ipratropium-Orphenadrine and Furosemide-Levosulpiride, not listed in Micromedex. The findings highlight the high prevalence of pDDIs in this population, emphasizing the need for regular monitoring. Using pDDI screening tools, clinical pharmacists can be crucial in mitigating these risks, particularly in high-risk patients.

This study assessed the occurrence and ecological potential risk of nine selected pharmaceuticals in water samples from the Juquehy River. The river flows continuously to Juquehy Beach, known as "the jewel of the north coast" of São Paulo, Brazil. Samples were collected during Christmas and the New Year (period of December 2023-January 2024), in addition to a previous baseline weekend, to compare the loads during "celebratory parties" versus "normal operational conditions." The findings indicated that the "mass gathering" during Christmas and New Year holidays contributed significantly to an increase of the mass load of the nine pharmaceuticals flowing along to the Juquehy River, i.e., caffeine (14.40-633.00 ng/L) > losartan (<LOQ: limit of quantification to 9.43 ng/L) > furosemide (< LOQ to 9.16 ng/L) > diclofenac (0.61-4.55 ng/L) > carbamazepine (< LOQ to 0.73 ng/L) > orphenadrine (< LOQ to 0.11 ng/L) showed higher concentrations during the New Year holiday. Conversely, atenolol (< LOQ to 13.10 ng/L) > benzoylecgonine (0.33-7.23 ng/L) > cocaine (0.12-6.59 ng/L) showed higher concentrations during the Christmas day. The individual ecological risk assessment in the Juquehy River revealed a clear environmental concern for the aquatic ecosystem. The threat to the aquatic biota is significant, with caffeine and losartan presenting a moderate level of risk. Moreover, the mixture ecological risk assessment of nine compounds indicates acute moderate risks to algae, crustaceans, and fishes, as well as chronic low risks to fishes.