2.Mining and analysis of lorlatinib-induced adverse drug event signals
Xia LONG ; Mengwen HUANG ; Shiyun PU ; Lichen WANG ; Mengjiao TANG ; Houfeng ZHOU
China Pharmacy 2023;34(20):2513-2518
OBJECTIVE To provide references for the safe use of lorlatinib in clinical practice. METHODS The reporting odds ratio (ROR) method, Medicines and Healthcare Products Regulatory Agency comprehensive standard method (referred to as “MHRA method”) and the Bayesian confidence propagation neural network (BCPNN) method were used to detect adverse drug events (ADEs) signals of lorlatinib in the FDA Adverse Event Reporting System from the first quarter of 2019 to the fourth quarter of 2022. RESULTS & CONCLUSIONS Totally 114 overlapping ADEs signals of lorlatinib were detected by the three methods, among which there were 73 new suspicious ADEs signals which were not covered in the instruction of lorlatinib. When using loratinib in clinical practice, special attention should be paid to ADEs with a high number of cases and signals, such as various neurological diseases, psychiatric diseases, respiratory system, thoracic and mediastinal diseases; clinical manifestations included cerebral edema, cerebral infarction, pulmonary hypertension, mutism, decreased sexual desire, pleural effusion. The signals of mobile thrombophlebitis, radiation necrosis, mutism, vesicoureteral reflux not mentioned in the instructions were all strong in BCPNN detection with high specificity, to which we should pay attention in clinical application.
3.Data mining of severe cutaneous adverse reactions related to immune checkpoint inhibitors in the FAERS
Xia LONG ; Mengwen HUANG ; Shiyun PU ; Lichen WANG ; Mengjiao TANG ; Houfeng ZHOU
China Pharmacy 2023;34(22):2760-2765
OBJECTIVE To mine and analyze severe cutaneous adverse reaction signals of 5 commonly used immune checkpoint inhibitors (ICIs), and to provide reference for clinically safe use of drugs. METHODS Based on the FDA adverse events reporting system (FAERS) database,adverse drug events (ADEs) reports about severe cutaneous adverse reactions related to ipilimumab, nivolumab, pembrolizumab, atezolizumab and durvalumab were collected from listing in the United States to the fourth quarter of 2022. The ADE signals were mined and analyzed with reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN). RESULTS A total of 5 726 reports of severe cutaneous adverse reactions were collected, including 3 037 reports for nivolumab,1 465 reports for pembrolizumab, 130 reports for durvalumab, 429 reports for atezolizumab and 665 reports for ipilimumab. All 5 kinds of ICIs caused positive signals, the correlation degree of which was as follows: pembrolizumab>atezolizumab>nivolumab>ipilimumab>durvalumab. Stevens-Johnson syndrome(SJS) and toxic epidermal necrolysis (TEN) have been reported for all 5 ICIs, and the association was the strongest with pembrolizumab. CONCLUSIONS All 5 kinds of ICIs are associated with the risk of severe skin adverse reactions, and close attention should be paid to their clinical use, especially being cautious when using pembrolizumab. The combination of ICIs should be avoided as much as possible.
4.Relationship Between NLRP3 Inflammasome and Diabetic Cardiomyopathy and Intervention Effect of Traditional Chinese Medicine: A Review
Sai ZHANG ; Zhengtao CHEN ; Shiyun TANG ; Chunguang XIE ; Lian DU ; Hong GAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):250-263
Diabetic cardiomyopathy (DCM) is one of the complications of diabetes. It refers to a specific type of idiopathic cardiomyopathy that occurs in individuals with diabetes, distinct from other cardiovascular diseases such as coronary heart disease, valvular heart disease, or congenital heart disease. It has also been identified as one of the leading causes of death in diabetic patients for many years. Research has shown that the pathogenesis of DCM is closely associated with insulin resistance, activation of various inflammatory responses, increased oxidative stress, impaired coronary microcirculation, and accumulation of advanced glycation end products (AGEs). Among various inflammatory responses, the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome can induce the secretion of a large amount of pro-inflammatory cytokines through the cascade reaction of inflammation, subsequently mediating cellular pyroptosis and promoting myocardial damage. Currently, extensive experimental studies on traditional Chinese medicine (TCM) have been conducted in China and abroad based on the significant role of the NLRP3 inflammasome in the prevention and treatment of DCM. These studies have demonstrated that Chinese medicinal extracts, such as Astragalus polysaccharide and ginsenoside Rb1, single drugs like Coriolus and Cordyceps, and Chinese medicinal formulas like Didangtang and modified Taohe Chengqitang, as well as acupuncture and TCM exercise therapy, can regulate the relevant pathways of the NLRP3 inflammasome to inhibit its assembly or activation, reduce inflammatory responses, inhibit myocardial remodeling in DCM, and improve cardiac function. This article reviewed the relationship between the NLRP3 inflammasome and DCM, as well as the research progress on TCM in exerting anti-inflammatory effects in this field, aiming to provide new insights for the development of therapeutic approaches for DCM.