Chronical Kidney Disease (CKD) causes deterioration of renal function with reduction of glomerular filtration (GFR). Drugs which are mainly excreted through the kidney have reduced renal elimination (Clrenal) in CKD. For decades dosage adjustments for these drugs have been computed based on GFR and clearance measurement of biomarker serum creatinine (Clcr), respectively, and according to the rule of Dettli [1-3] where the appropriate dose D compared to the normal dose (Dnorm) may be assessed through the individual elimination fraction Q:
Introduction: Pain alleviation is the primary intervention in promoting quality of life. Among the compounds used in management of pain are opioids. Codeine is mostly used as antitussive and is commonly present in cough syrups. Tramadol and Morphine are used as analgesics based on severity of pain. Although these drugs provide instant pain relief, they are associated with many side effects and the most worrying once are addiction, respiratory depression and tolerance. Methods: Codeine, Tramadol, and Morphine were used as query compounds to generate similar compounds using SwissSimilarity. Similar compounds were docked to mu, kappa, and delta receptors and those that showed better docking scores to mu receptor and lower scores to kappa and delta were analyzed for toxicity profiles using ProTox II and pharmacokinetics profiles using SwissADME. Results: ZINC13831510; 0.992, ZINC03629718; 0. 995; ZINC03870350; 0.993; ZINC28256912; 0.992; and ZINC71774151; 0.977 showed highest binding score to mu receptors and lower to both kappa and delta. All compounds were predicted to inhibit CYP2D6 enzyme. All compounds permeated Blood Brain Barrier with the exceptions of ZINC04102208; 0.992; and ZINC13831510; 0.992. Tramadol, its zinc compounds and ZINC03629718; 0.995. were not substrates for P-glycoprotein. Tramadol and ZINC03639132; 0.976; were predicted immunoactive. All compounds conformed to Lipinski rule of five. Conclusion: In conclusion, ZINC13831510; 0.992; showed the highest binding score to morphine. ZINC02509756; 0.986; and ZINC26259212; 0.995; were considered the safest as compared to Tramadol and Codeine and their zinc compounds respectively. Further invitro studies are recommended for the following promising compounds ZINC13831510; 0.992, ZINC03629718; 0. 995; ZINC03870350; 0.993; ZINC28256912; 0.992; and ZINC71774151; 0.977 ZINC02509756; 0.986; and ZINC26259212; 0.995;.
In COPD, chronic inflammation and exposure to irritants, such as cigarette smoke, lead to the thickening of bronchial walls. This results from increased deposition of collagen and other extracellular matrix components, contributing to the narrowing of airways. Nevertheless, it is widely recognized that COPD is an inflammatory disorder marked by partially reversible airflow limitation wherein genetic factors interact with the environment. In recent years, numerous investigations have substantiated the correlation between gene polymorphisms and COPD. SUMF1 has been implicated in diverse cellular processes, including lysosomal function and extracellular matrix maintenance, both of which play pivotal roles in respiratory health. The genetic variations in SUMF1 could lead to an imbalanced sulfation in the extracellular matrix of lung tissue, potentially playing a role in the onset of COPD. Recent studies have uncovered a potential link between dysregulation of SUMF1 and COPD progression, shedding light on its involvement in the abnormal sulfatase activity observed in COPD patients. Through a comprehensive review of current literature and experimental findings, this article aims to contribute to the growing body of knowledge surrounding the genetic intricacies concerning sulfation of airway remodeling and possible pharmacological applications in COPD and asthma management.
1,4-napthoquinone and its derivatives possess significant anticancer, antinociceptive and antimicrobial activities and thus modification of 1,4-napthquinonone might result in generation of a lead compound for the development of more effective drug therapy against cancer, pain disorders and bacterial infections. In the present study, 2-methylamino-{3-[2-(4-morpholinyl)-ethyl]-amino}-1,4- Naphthoquinone was synthesized and then evaluated for cytotoxic, antimicrobial and antinociceptive activity. In MTT-based cytotoxicity assay, the compound exhibited strong cytotoxic activity against HeLa cell line with a LD50 value of 17.5μg/ml. In antimicrobial susceptibility test performed by agar disc diffusion method, the compound exhibited promising antibacterial activity against both Grampositive and Gram-negative bacteria with 17-20mm of diameter of zone of inhibition suggesting that the synthesized compound possesses a broad spectrum of antibacterial activity. The compound also demonstrated promising antifungal activities against Saccharoromyces cerevisiae, Candida albicans and Aspergillus nigar. In the acetic acid-induced writhing test in mice, at a dose of 50 mg/kg body weight, the compound displayed significant analgesic activity with 68.3% writhing inhibition which was comparable to that of the standard aceclofenac. These results suggested that the synthesized napthoquionone analog possesses remarkable cytotoxic, antinociceptive and antimicrobial activities and thus could be a potential lead for the development of drug against cancer, infections and pain disorders.
Objective: Determine the distribution and longitudinal changes in antihypertensive medication regimens in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods: We used antihypertensive medication data collected by pill bottle review at each visit to categorize antihypertensive regimens by medication class. Free text string variables of medication names were independently reviewed by two clinical pharmacists to create standardized generic medication names and classes. Results: Figure 1 illustrates longitudinal changes in class combinations and number of drugs at the randomization, 6, 12, and 18-month visits. Fifty-six percent of participants modified their initial regimen by the 6-month visits; 43% of participants made additional modifications to their regimens from the 6-month to the 18-month visit. The most common initial regimens, and least likely regimens to be changed over time, were combinations with an ACEI/ARB and diuretics ± other classes (42% of initial regimens). Participants in the intensive arm added a mean (standard deviation) of 0.6 (0.9) medications to their initial regimens in the first 18-months compared to -0.1 (0.9) in the standard arm. Conclusion: Intensive blood pressure treatment requires more medication complexity in terms of class and dose. Further study of distinct regimens may reveal if certain class and dose combinations provide better SBP control, safety, or patient satisfaction.
