ABSTRACT
Heterocyclic scaffolds of natural as well as synthetic origin provide almost all categories of drugs exhibiting a wide range of pharmacological activities, such as antibiotics, antidiabetic and anticancer agents, and so on. Under normal homeostasis, aldose reductase 2 (ALR2) regulates vital metabolic functions; however, in pathological conditions like diabetes, ALR2 is unable to function and leads to secondary diabetic complications. ALR2 inhibitors are a novel target for the treatment of retinopathy (cataract) influenced by diabetes. Epalrestat (stat), an ALR2 inhibitor, is the only drug candidate that was approved in the last four decades; the other drugs from the stat class were retracted after clinical trial studies due to untoward iatrogenic effects. The present study summarizes the recent development (2014 and onwards) of this pharmacologically active ALR2 heterocyclic scaffold and illustrates the rationale behind the design, structure-activity relationships, and biological studies performed on these molecules. The aim of the current review is to pave a straight path for medicinal chemists and chemical biologists, and, in general, to the drug discovery scientists to facilitate the synthesis and development of novel ALR2 inhibitors that may serve as lead molecules for the treatment of diseases related to the ALR2 enzyme.
Subject(s)
Aldehyde Reductase , Enzyme Inhibitors , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Hypoglycemic Agents/pharmacology , Structure-Activity Relationship , Clinical Trials as TopicABSTRACT
INTRODUCTION: Drug utilization of analgesics in a private healthcare setting is useful to examine their prescribing patterns, especially the newer injectable cyclooxygenase (COX)-2 inhibitors (coxibs). OBJECTIVES: To evaluate the utilization of coxibs and traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) indicated for postoperative orthopaedic pain control using defined daily dose (DDD) and ratio of use density to use rate (UD/UR). METHOD: A retrospective drug utilization review (DUR) of nonsteroidal anti-inflammatory drugs (NSAIDs) at an inpatient department of a private teaching hospital in Seremban, Malaysia was conducted. Patients' demographic characteristics, medications prescribed, clinical lab results, visual analogue scale (VAS) pain scores and length of hospital stay were documented. Orthopaedic surgeries, namely arthroscopy, reconstructive, and fracture fixation, were included. Stratified random sampling was used to select patients. Data were collected through patients' medical records. The DDD per 100 admissions and the indicator UD/UR were calculated with the World Health Organization's DDD as a benchmark. The inclusion criteria were patients undergoing orthopaedic surgery prescribed with coxibs (celecoxib capsules, etoricoxib tablets, parecoxib injections) and tNSAIDs (dexketoprofen injections, diclofenac sodium tablets). Data were analysed descriptively. This research was approved by the academic institution and the hospital research ethics committee. RESULT: A total of 195 records of patients who received NSAIDs were randomly selected among 1169 cases. In term of the types of orthopaedic surgery, the ratio of included records for arthroscopy:fracture fixation:reconstructive surgery was 55.4:35.9:8.7. Most of the inpatients had low rates of common comorbidities such as cardiovascular disease as supported by their baseline parameters. The majority were not prescribed with other concomitant prescriptions that could cause drug interaction (74.9%), or gastroprotective agents (77.4%). Overall, DDDs per 100 admissions for all NSAIDs were less than 100, except for parecoxib injections (389.23). The UD/UR for all NSAIDs were less than 100, except for etoricoxib tablets (105.75) and parecoxib injections (108.00). DISCUSSION: As per guidelines, the majority (96.9%) received other analgesics to ensure a multimodal approach was carried out to control pain. From the UD/UR results, the arthroscopy surgery was probably the most appropriate in terms of NSAID utilization. CONCLUSION: The prescribing pattern of NSAIDs except parecoxib was appropriate based on adverse effect and concurrent medication profile. The findings of this DUR provide insight for a low-risk patient population at a private specialized teaching hospital on the recommended use of NSAIDs for postoperative orthopaedic pain control.
