Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we...Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.展开更多
Human life expectancy increases as society becomes more developed.This increased life expectancy poses challenges associated with the rapid aging of the population.Sarcopenia,an age-related disease,has become a worldw...Human life expectancy increases as society becomes more developed.This increased life expectancy poses challenges associated with the rapid aging of the population.Sarcopenia,an age-related disease,has become a worldwide health issue.Patients with sarcopenia experience decreases in muscle mass and function,becoming frail and eventually bedridden.Type 2 diabetes mellitus(T2DM)is also a major health issue;the incidence of T2DM increases with aging.T2DM is associated with reduced muscle strength and poor muscle quality and may contribute to acceleration of the aging process,augmenting age-related sarcopenia.Recent studies indicate that elderly patients with diabetes are at an increased risk for sarcopenia.Therefore,these older diabetic patients with sarcopenia need specific anti-diabetic therapies targeting not only glycemic control but also sarcopenia,with the goal of preventing sarcopenia in presarcopenic patients.Presently,various types of hypoglycemic drugs are available,but which hypoglycemic drugs are better suited for geriatric T2DM patients with sarcopenia remains undetermined.In this review,we discuss the association between diabetes and sarcopenia in geriatric patients,and how anti-diabetic drugs may influence sarcopenia outcomes.This review will guide clinical workers in the selection of drugs best suited for this patient population.展开更多
Recent clinical trials indicated that the intensive glycemic control do not reduce cardiovascular disease mortality among diabetic patients, challenging a significance of the strict glycemic control in diabetes manage...Recent clinical trials indicated that the intensive glycemic control do not reduce cardiovascular disease mortality among diabetic patients, challenging a significance of the strict glycemic control in diabetes management. Furthermore, retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes study demonstrated a significant association betweenhypoglycemia and mortality. Here, we systematically reviewed the drug-induced hypoglycemia, and also the underlying clinical factors for hypoglycemia in patients with diabetes. The sulfonylurea use is significantly associated with severe hypoglycemia in patients with type 2 diabetes. The use of biguanide(approximately 45%-76%) and thiazolidinediones(approximately 15%-34%) are also highly associated with the development of severe hypoglycemia. In patients treated with insulin, the intensified insulin therapy is more frequently associated with severe hypoglycemia than the conventional insulin therapy and continuous subcutaneous insulin infusion. Among the underlying clinical factors for development of severe hypoglycemia, low socioeconomic status, aging, longer duration of diabetes, high Hb A1 c and low body mass index, comorbidities are precipitating factors for severe hypoglycemia. Poor cognitive and mental functions are also associated with severe hypoglycemia.展开更多
Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop respondi...Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.展开更多
The objective of this study is to utilize the pH sensitivity of modified silica nanoparticles (SNIL) by imidazole-based ionic liquid for oral delivery of insulin. In the first time, the imidazole was covalently attach...The objective of this study is to utilize the pH sensitivity of modified silica nanoparticles (SNIL) by imidazole-based ionic liquid for oral delivery of insulin. In the first time, the imidazole was covalently attached to the 3-trimethoxysily-lpropyl chloride with replacement of all the chlorine atoms. Then, a silica nanoparticle was modified by N-(3-trimeth-oxysilylpropyl) imidazole. The nanocapsule (NCIL) was achieved after the etching of the modified silica nanoparticle template with hydrofluoric acid. The nanoparticles connected through an ionic liquid-like network were characterized by FTIR and SEM. Insulin was entrapped in these carriers and the in vitro release profiles were established separately in both enzyme-free simulated gastric and intestinal fluids (SGF, pH 1) and (SIF, pH 7.4), respectively. When these drug-loaded nanoparticles was placed in physiological buffer solution (pH 7.4), a partial negative surface charge on the modified silica nanoparticle was generated due to the deprotonation of silanol groups, and the strong electrostatic repulsion triggered a sustained release of the loaded molecules.展开更多
An oral drug delivery system using proteinoid microspheres is discussed with respect to itsunique dependence on pH. It has been found that certain drugs such as insulin and heparin canbe encapsulated in proteinoid sph...An oral drug delivery system using proteinoid microspheres is discussed with respect to itsunique dependence on pH. It has been found that certain drugs such as insulin and heparin canbe encapsulated in proteinoid spheres at stomach pH's (1--3). These spheres also dissemble atintestinal pH's (6--7) releasing the drug for absorption. Using this technique low molecularweight heparin and human growth hormone have been orally delivered successfully to severalanimal species. Future work has been proposed to study the interaction and binding of thespecific drugs with synthesized oligopeptides.展开更多
Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown extensively.In short,personalized medicine is a term that describes medical trea...Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown extensively.In short,personalized medicine is a term that describes medical treatment that is tuned to the individual.One possible way to realize personalized medicine is 3D printing.When using materials that can be tuned upon stimulation,4D printing is established.In recent years,many studies have been exploring a new field that combines 3D and 4D printing with therapeutics.This has resulted in many concepts of pharmaceutical devices and formulations that can be printed and,possibly,tailored to an individual.Moreover,the first 3D printed drug,Spritam®,has already found its way to the clinic.This review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine.展开更多
Diabetes is a chronic metabolic disease reaching an epidemic proportion in many parts of the world. By the year 2025 it is expected that 333 million people of the world will have diabetes as their main ailment. As tod...Diabetes is a chronic metabolic disease reaching an epidemic proportion in many parts of the world. By the year 2025 it is expected that 333 million people of the world will have diabetes as their main ailment. As today, India assumes the position of the diabetic capital of the world with the highest percentage of its population suffering from diabetes. It is pathetic to mention that in proportion to its people suffering from diabetes, this country has very weak spending power for treatment because of wide spread poverty. Therefore, this review is aimed at opening up new vistas in realizing the therapeutic potential of Ayurveda in treatment of diabetes and other chronic diseases. All drugs which we have discussed in this review have a significant role in therapy of diabetes mellitus.展开更多
BACKGROUND Gastric lavage(GL)is one of the most important early therapies to remove unabsorbed toxins from the gastrointestinal tract.However,the details of performing gastric lavage remain to be established.There is ...BACKGROUND Gastric lavage(GL)is one of the most important early therapies to remove unabsorbed toxins from the gastrointestinal tract.However,the details of performing gastric lavage remain to be established.There is controversy in clinical practice regarding individual choice of the timing of GL and its efficiency.CASE SUMMARY We report the case of a young woman who presented to the Emergency Department with drug intoxication for four hours.We used the latest toxicological screening techniques to compare drug concentrations in the patient's blood and gastric lavage fluid before and after gastric lavage.The results confirmed that gastric lavage was effective in reducing drug concentrations in the stomach;a small amount of drug remained in the stomach at the end of gastric lavage.CONCLUSION Gastric lavage is effective in reducing drug concentrations in the stomach,with a small amount of drug remaining in the stomach at the end of gastric lavage.展开更多
<strong>Background:</strong> Diabetes mellitus (DM) is a syndrome of chronically elevated glucose level in the blood either due to insulin resistance, insulin deficiency or both. In addition, it may occur ...<strong>Background:</strong> Diabetes mellitus (DM) is a syndrome of chronically elevated glucose level in the blood either due to insulin resistance, insulin deficiency or both. In addition, it may occur due to defective metabolism of carbohydrates, fats and proteins. There are 3 main types of DM: Type 2 DM is more prevalent in adults and is typically due to relative insulin deficiency, deficiency of insulin in children leads to DM type 1;and lastly, gestational diabetes occurs during pregnancy resulting from an imbalance of placental hormones. <strong>Introduction:</strong> Insulin, Biguanides and Sulfonylureas are some of the drug classes used to treat DM. However, their use is complicated by numerous side effects, such as;hypoglycemia & weight gain from insulin and sulfonylureas;lactic acidosis, vitamin B12 deficiency and gastrointestinal upset with metformin. Route of administration and cost are also important factors to consider when prescribing. It is for this reason the quest for newer, safer and easier to administer drugs is ongoing. <strong>Methodology:</strong> Used all the articles available on anti Diabetic drugs on web especially in British Medical Journal, Elsevier, Pubmed, Google scholar and Wikipedia etc. Got a final review article to compare the older and newer anti Diabetic drugs. <strong>Results and Conclusion:</strong> Insulin is good for controlling acute hyperglycemic states in DM but it causes acute hypoglycemia and lipodystrophy. Metformin is good hypoglycemic and easily available but causes hypoglycemia, metallic taste, Lactic acidosis and B12 deficiency. Sulfonylureas are good hypoglycemic but causes severe hypoglycemia acutely and weight gain so contraindicated for obese or hypertensive patients. While newer antidiabetics such as GLP 1 agonists increases insulin secretions has very low risk of hypoglycemia, causes weight loss as compared to insulin and decreases risk of cardiovascular side effects but still can’t be used in renally impaired patients, causes pancreatitis and can not be given in gastroparesis patients, similarly a newer drug of this class known as LY2189265 has long halflife of 90 hours, better efficacy, but causes pancreatitis and increase diastolic BP in high doses, pancreatitis is not associated with lixisenatide (GLP 1 agonist), while DPP4 inhibitors which increases GLP 1 in body has less risk of hypoglycemia, GI side effects, are weight neutral can be used in CKD but causes headaches and Nasopharyngitis. Bromocriptine or pegvisomant are used in patients of growth hormones adenoma induced DM as a medical therapy but are associated with psychosis and hallucinations. Meglitinides increases insulin secretion and has minuscule risk of hypoglycemia but can not be used in CKD patients. Otelixizumab and Teplizumab decrease T cell functions and save beta cells from immune reactions used in DM 1 but cause immune suppression and is an orphan drug. Recombinant GAD used in vaccines decreased antibody mediated beta cell damage but is still under studies.展开更多
BACKGROUND Drug-induced liver injury(DILI)can be caused by any prescribed drug and is a significant reason for the withdrawal of newly launched drugs.Direct-acting oral anticoagulants(DOACs)are non-vitamin K-based ant...BACKGROUND Drug-induced liver injury(DILI)can be caused by any prescribed drug and is a significant reason for the withdrawal of newly launched drugs.Direct-acting oral anticoagulants(DOACs)are non-vitamin K-based antagonists recently introduced and increasingly used for various clinical conditions.A meta-analysis of 29 randomised controlled trials and 152116 patients reported no increased risk of DILI with DOACs.However,it is challenging to predict the risk factors for DILI in individual patients with exclusion of patients with pre-existing liver disease from these studies.AIM To determine the risk factors and outcomes of patients who developed DILI secondary to DOACs by systematic review and meta-summary of recent case reports and series.METHODS A systematic search was conducted on multiple databases including PubMed,Science Direct,Reference Citation Analysis,and Google Scholar.The search terms included“Acute Liver Failure”OR“Acute-On-Chronic Liver Failure”OR“Acute Chemical and Drug Induced Liver Injury”OR“Chronic Chemical and Drug Induced Liver Injury”AND“Factor Xa Inhibitors”OR“Dabigatran”OR“Rivaroxaban”OR“apixaban”OR“betrixaban”OR“edoxaban”OR“Otamixaban”.The results were filtered for literature published in English and on adult patients.Only case reports and case studies reporting cases of DILI secondary to DOACs were included.Data on demographics,comorbidities,medication history,laboratory investigations,imaging,histology,management,and outcomes were extracted.RESULTS A total of 15 studies(13 case reports and 2 case series)were included in the analysis,comprising 27 patients who developed DILI secondary to DOACs.Rivaroxaban was the most commonly implicated DOAC(n=20,74.1%).The mean time to onset of DILI was 40.6 d.The most common symptoms were jaundice(n=15,55.6%),malaise(n=9,33.3%),and vomiting(n=9,33.3%).Laboratory investigations showed elevated liver enzymes and bilirubin levels.Imaging studies and liver biopsies revealed features of acute hepatitis and cholestatic injury.Most patients had a favourable outcome,and only 1 patient(3.7%)died due to liver failure.CONCLUSION DOACs are increasingly used for various clinical conditions,and DILI secondary to DOACs is a rare but potentially serious complication.Prompt identification and cessation of the offending drug are crucial for the management of DILI.Most patients with DILI secondary to DOACs have a favourable outcome,but a small proportion may progress to liver failure and death.Further research,including post-marketing population-based studies,is needed to better understand the incidence and risk factors for DILI secondary to DOACs.展开更多
目的系统评价癌症相关静脉血栓栓塞(VTE)患者使用新型口服抗凝剂(NOAC)的有效性和安全性。方法检索PubMed、Cochrane Library、Embase、Web of Science、中国知网、万方数据库,检索时限为各数据库建库起至2023年8月,收集低分子肝素(LMWH...目的系统评价癌症相关静脉血栓栓塞(VTE)患者使用新型口服抗凝剂(NOAC)的有效性和安全性。方法检索PubMed、Cochrane Library、Embase、Web of Science、中国知网、万方数据库,检索时限为各数据库建库起至2023年8月,收集低分子肝素(LMWH,对照组)对比NOAC(试验组)治疗癌症相关VTE患者疗效的随机对照试验(RCT),对纳入临床研究进行资料提取后,采用RevMan 5.0统计软件进行Meta分析。结果共计纳入7项RCT,合计3790例癌症相关VTE患者。与对照组相比,试验组患者的VTE复发率(RR=0.65,95%CI为0.51~0.82,P=0.0004)显著降低,而其大出血发生率略高于对照组,但差异无统计学意义(RR=1.13,95%CI为0.83~1.53,P=0.45)。试验组患者的临床相关非主要大出血(RR=1.69,95%CI为1.34~2.13,P<0.00001)、消化道出血(RR=1.96,95%CI为1.15~3.34,P=0.01)发生率均较对照组显著升高。两组患者颅内出血发生率、全因死亡率、致死性肺栓塞发生率比较,差异均无统计学意义(P>0.05)。结论对于癌症相关VTE患者,NOAC在预防VTE复发方面优于LMWH,在大出血、颅内出血、全因死亡、致死性肺栓塞方面不劣于LMWH。展开更多
基金The authors gratefully acknowledge financial support from National Natural Science Foundation of China(81872818)National Key R&D Program of China(2021YFE0115200).
文摘Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.
基金Supported by National Natural Science Foundation of China,No.81600693.
文摘Human life expectancy increases as society becomes more developed.This increased life expectancy poses challenges associated with the rapid aging of the population.Sarcopenia,an age-related disease,has become a worldwide health issue.Patients with sarcopenia experience decreases in muscle mass and function,becoming frail and eventually bedridden.Type 2 diabetes mellitus(T2DM)is also a major health issue;the incidence of T2DM increases with aging.T2DM is associated with reduced muscle strength and poor muscle quality and may contribute to acceleration of the aging process,augmenting age-related sarcopenia.Recent studies indicate that elderly patients with diabetes are at an increased risk for sarcopenia.Therefore,these older diabetic patients with sarcopenia need specific anti-diabetic therapies targeting not only glycemic control but also sarcopenia,with the goal of preventing sarcopenia in presarcopenic patients.Presently,various types of hypoglycemic drugs are available,but which hypoglycemic drugs are better suited for geriatric T2DM patients with sarcopenia remains undetermined.In this review,we discuss the association between diabetes and sarcopenia in geriatric patients,and how anti-diabetic drugs may influence sarcopenia outcomes.This review will guide clinical workers in the selection of drugs best suited for this patient population.
基金Supported by A grant from the National Center for Global Health and Medicine(25-203)
文摘Recent clinical trials indicated that the intensive glycemic control do not reduce cardiovascular disease mortality among diabetic patients, challenging a significance of the strict glycemic control in diabetes management. Furthermore, retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes study demonstrated a significant association betweenhypoglycemia and mortality. Here, we systematically reviewed the drug-induced hypoglycemia, and also the underlying clinical factors for hypoglycemia in patients with diabetes. The sulfonylurea use is significantly associated with severe hypoglycemia in patients with type 2 diabetes. The use of biguanide(approximately 45%-76%) and thiazolidinediones(approximately 15%-34%) are also highly associated with the development of severe hypoglycemia. In patients treated with insulin, the intensified insulin therapy is more frequently associated with severe hypoglycemia than the conventional insulin therapy and continuous subcutaneous insulin infusion. Among the underlying clinical factors for development of severe hypoglycemia, low socioeconomic status, aging, longer duration of diabetes, high Hb A1 c and low body mass index, comorbidities are precipitating factors for severe hypoglycemia. Poor cognitive and mental functions are also associated with severe hypoglycemia.
文摘Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.
文摘The objective of this study is to utilize the pH sensitivity of modified silica nanoparticles (SNIL) by imidazole-based ionic liquid for oral delivery of insulin. In the first time, the imidazole was covalently attached to the 3-trimethoxysily-lpropyl chloride with replacement of all the chlorine atoms. Then, a silica nanoparticle was modified by N-(3-trimeth-oxysilylpropyl) imidazole. The nanocapsule (NCIL) was achieved after the etching of the modified silica nanoparticle template with hydrofluoric acid. The nanoparticles connected through an ionic liquid-like network were characterized by FTIR and SEM. Insulin was entrapped in these carriers and the in vitro release profiles were established separately in both enzyme-free simulated gastric and intestinal fluids (SGF, pH 1) and (SIF, pH 7.4), respectively. When these drug-loaded nanoparticles was placed in physiological buffer solution (pH 7.4), a partial negative surface charge on the modified silica nanoparticle was generated due to the deprotonation of silanol groups, and the strong electrostatic repulsion triggered a sustained release of the loaded molecules.
文摘An oral drug delivery system using proteinoid microspheres is discussed with respect to itsunique dependence on pH. It has been found that certain drugs such as insulin and heparin canbe encapsulated in proteinoid spheres at stomach pH's (1--3). These spheres also dissemble atintestinal pH's (6--7) releasing the drug for absorption. Using this technique low molecularweight heparin and human growth hormone have been orally delivered successfully to severalanimal species. Future work has been proposed to study the interaction and binding of thespecific drugs with synthesized oligopeptides.
文摘Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown extensively.In short,personalized medicine is a term that describes medical treatment that is tuned to the individual.One possible way to realize personalized medicine is 3D printing.When using materials that can be tuned upon stimulation,4D printing is established.In recent years,many studies have been exploring a new field that combines 3D and 4D printing with therapeutics.This has resulted in many concepts of pharmaceutical devices and formulations that can be printed and,possibly,tailored to an individual.Moreover,the first 3D printed drug,Spritam®,has already found its way to the clinic.This review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine.
文摘Diabetes is a chronic metabolic disease reaching an epidemic proportion in many parts of the world. By the year 2025 it is expected that 333 million people of the world will have diabetes as their main ailment. As today, India assumes the position of the diabetic capital of the world with the highest percentage of its population suffering from diabetes. It is pathetic to mention that in proportion to its people suffering from diabetes, this country has very weak spending power for treatment because of wide spread poverty. Therefore, this review is aimed at opening up new vistas in realizing the therapeutic potential of Ayurveda in treatment of diabetes and other chronic diseases. All drugs which we have discussed in this review have a significant role in therapy of diabetes mellitus.
基金Early Diagnosis of Venom-Induced Ventricular Fascia Syndrome Based on High Frequency Ultrasound and Shear Wave Elastography,No.2021YFS0189.
文摘BACKGROUND Gastric lavage(GL)is one of the most important early therapies to remove unabsorbed toxins from the gastrointestinal tract.However,the details of performing gastric lavage remain to be established.There is controversy in clinical practice regarding individual choice of the timing of GL and its efficiency.CASE SUMMARY We report the case of a young woman who presented to the Emergency Department with drug intoxication for four hours.We used the latest toxicological screening techniques to compare drug concentrations in the patient's blood and gastric lavage fluid before and after gastric lavage.The results confirmed that gastric lavage was effective in reducing drug concentrations in the stomach;a small amount of drug remained in the stomach at the end of gastric lavage.CONCLUSION Gastric lavage is effective in reducing drug concentrations in the stomach,with a small amount of drug remaining in the stomach at the end of gastric lavage.
文摘<strong>Background:</strong> Diabetes mellitus (DM) is a syndrome of chronically elevated glucose level in the blood either due to insulin resistance, insulin deficiency or both. In addition, it may occur due to defective metabolism of carbohydrates, fats and proteins. There are 3 main types of DM: Type 2 DM is more prevalent in adults and is typically due to relative insulin deficiency, deficiency of insulin in children leads to DM type 1;and lastly, gestational diabetes occurs during pregnancy resulting from an imbalance of placental hormones. <strong>Introduction:</strong> Insulin, Biguanides and Sulfonylureas are some of the drug classes used to treat DM. However, their use is complicated by numerous side effects, such as;hypoglycemia & weight gain from insulin and sulfonylureas;lactic acidosis, vitamin B12 deficiency and gastrointestinal upset with metformin. Route of administration and cost are also important factors to consider when prescribing. It is for this reason the quest for newer, safer and easier to administer drugs is ongoing. <strong>Methodology:</strong> Used all the articles available on anti Diabetic drugs on web especially in British Medical Journal, Elsevier, Pubmed, Google scholar and Wikipedia etc. Got a final review article to compare the older and newer anti Diabetic drugs. <strong>Results and Conclusion:</strong> Insulin is good for controlling acute hyperglycemic states in DM but it causes acute hypoglycemia and lipodystrophy. Metformin is good hypoglycemic and easily available but causes hypoglycemia, metallic taste, Lactic acidosis and B12 deficiency. Sulfonylureas are good hypoglycemic but causes severe hypoglycemia acutely and weight gain so contraindicated for obese or hypertensive patients. While newer antidiabetics such as GLP 1 agonists increases insulin secretions has very low risk of hypoglycemia, causes weight loss as compared to insulin and decreases risk of cardiovascular side effects but still can’t be used in renally impaired patients, causes pancreatitis and can not be given in gastroparesis patients, similarly a newer drug of this class known as LY2189265 has long halflife of 90 hours, better efficacy, but causes pancreatitis and increase diastolic BP in high doses, pancreatitis is not associated with lixisenatide (GLP 1 agonist), while DPP4 inhibitors which increases GLP 1 in body has less risk of hypoglycemia, GI side effects, are weight neutral can be used in CKD but causes headaches and Nasopharyngitis. Bromocriptine or pegvisomant are used in patients of growth hormones adenoma induced DM as a medical therapy but are associated with psychosis and hallucinations. Meglitinides increases insulin secretion and has minuscule risk of hypoglycemia but can not be used in CKD patients. Otelixizumab and Teplizumab decrease T cell functions and save beta cells from immune reactions used in DM 1 but cause immune suppression and is an orphan drug. Recombinant GAD used in vaccines decreased antibody mediated beta cell damage but is still under studies.
文摘BACKGROUND Drug-induced liver injury(DILI)can be caused by any prescribed drug and is a significant reason for the withdrawal of newly launched drugs.Direct-acting oral anticoagulants(DOACs)are non-vitamin K-based antagonists recently introduced and increasingly used for various clinical conditions.A meta-analysis of 29 randomised controlled trials and 152116 patients reported no increased risk of DILI with DOACs.However,it is challenging to predict the risk factors for DILI in individual patients with exclusion of patients with pre-existing liver disease from these studies.AIM To determine the risk factors and outcomes of patients who developed DILI secondary to DOACs by systematic review and meta-summary of recent case reports and series.METHODS A systematic search was conducted on multiple databases including PubMed,Science Direct,Reference Citation Analysis,and Google Scholar.The search terms included“Acute Liver Failure”OR“Acute-On-Chronic Liver Failure”OR“Acute Chemical and Drug Induced Liver Injury”OR“Chronic Chemical and Drug Induced Liver Injury”AND“Factor Xa Inhibitors”OR“Dabigatran”OR“Rivaroxaban”OR“apixaban”OR“betrixaban”OR“edoxaban”OR“Otamixaban”.The results were filtered for literature published in English and on adult patients.Only case reports and case studies reporting cases of DILI secondary to DOACs were included.Data on demographics,comorbidities,medication history,laboratory investigations,imaging,histology,management,and outcomes were extracted.RESULTS A total of 15 studies(13 case reports and 2 case series)were included in the analysis,comprising 27 patients who developed DILI secondary to DOACs.Rivaroxaban was the most commonly implicated DOAC(n=20,74.1%).The mean time to onset of DILI was 40.6 d.The most common symptoms were jaundice(n=15,55.6%),malaise(n=9,33.3%),and vomiting(n=9,33.3%).Laboratory investigations showed elevated liver enzymes and bilirubin levels.Imaging studies and liver biopsies revealed features of acute hepatitis and cholestatic injury.Most patients had a favourable outcome,and only 1 patient(3.7%)died due to liver failure.CONCLUSION DOACs are increasingly used for various clinical conditions,and DILI secondary to DOACs is a rare but potentially serious complication.Prompt identification and cessation of the offending drug are crucial for the management of DILI.Most patients with DILI secondary to DOACs have a favourable outcome,but a small proportion may progress to liver failure and death.Further research,including post-marketing population-based studies,is needed to better understand the incidence and risk factors for DILI secondary to DOACs.
文摘目的系统评价癌症相关静脉血栓栓塞(VTE)患者使用新型口服抗凝剂(NOAC)的有效性和安全性。方法检索PubMed、Cochrane Library、Embase、Web of Science、中国知网、万方数据库,检索时限为各数据库建库起至2023年8月,收集低分子肝素(LMWH,对照组)对比NOAC(试验组)治疗癌症相关VTE患者疗效的随机对照试验(RCT),对纳入临床研究进行资料提取后,采用RevMan 5.0统计软件进行Meta分析。结果共计纳入7项RCT,合计3790例癌症相关VTE患者。与对照组相比,试验组患者的VTE复发率(RR=0.65,95%CI为0.51~0.82,P=0.0004)显著降低,而其大出血发生率略高于对照组,但差异无统计学意义(RR=1.13,95%CI为0.83~1.53,P=0.45)。试验组患者的临床相关非主要大出血(RR=1.69,95%CI为1.34~2.13,P<0.00001)、消化道出血(RR=1.96,95%CI为1.15~3.34,P=0.01)发生率均较对照组显著升高。两组患者颅内出血发生率、全因死亡率、致死性肺栓塞发生率比较,差异均无统计学意义(P>0.05)。结论对于癌症相关VTE患者,NOAC在预防VTE复发方面优于LMWH,在大出血、颅内出血、全因死亡、致死性肺栓塞方面不劣于LMWH。
