Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug-drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug-drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.

Prevalence of Drug Interactions and Potentially Inappropriate Medications Among Geriatric Patients in India.

Aim: The study aimed to determine the prevalence of potential drug-drug interactions (PDDIs) and potentially inappropriate medications (PIMs) among geriatrics. Methods: A prospective observational study was conducted for six months in the Department of Geriatrics, M.S. Ramaiah Teaching Hospital, Bangalore. PDDIs and PIMS were analyzed using micromedex database and Beer's criteria respectively. Results: Among 395 prescriptions, 221(56%) prescriptions showed 559 pDDIs and 41(10.4%) PIMs. Almost 281(50.3%), 260(46.5%), 16(2.7%) and 2(0.3%) pDDIs were categorised as major, moderate, minor and contraindicated respectively. Almost 321(57.5%) were synergistic and 196(35.0%) were antagonistic drug interactions. Pearson correlation value (R) is 0.9957 which showed a strong positive correlation. Conclusion: This study created awareness on drug interactions among geriatrics and help the practitioners to prescribe drugs with a low risk of pDDIs. The authors suggest PIM monitoring in geriatrics to avoid adverse effects and improve patients' quality of life.

An observational study on potential drug-drug interaction among hypertensive patients in a tertiary care hospital

Background: Drug-drug interactions are quite prevalent, especially in the geriatric population with comorbidities. It affects the effectiveness, safety, and tolerability of the medications they use. Aims and Objectives: This study aims to analyze and identify potential drug-drug interactions (pDDIs) in hypertensive patients using Medscape databases. Materials and Methods: A prospective and observational study was conducted in the Hypertension clinic of KMC, Chennai, for 3 months during November 2019–January 2020. Hypertensive patients of both sexes attending hypertension clinics with an age of more than 18 years and taking more than two antihypertensive drugs were included in the study. The use of Medscape databases enabled the appropriate data to be gathered and evaluated for pDDIs. Results: Three hundred patients in all were enrolled for the trial. One hundred and forty out of the 300 patients had pDDIs. Out of 140 patients, the majority (55%) were between the ages of 40 and 60. Males (56.4%) had a higher prevalence of pDDIs than females (43.6%). Atenolol, enalapril, and furosemide were the most frequently used medications in the present study that caused pDDIs, accounting for 29.8%, 19.5%, and 18.6%, respectively. Conclusion: The prevalence of pDDIs was found to be 46.6% overall, and an increase in comorbidities and polypharmacy were revealed to be important risk factors for the emergence of several pDDIs. Most of the antihypertensives were shown to interact frequently with calcium carbonate.

Predictores de potenciales reacciones adversas e interacciones medicamentosas en pacientes post accidente cerebrovascular en Perú

Objetivo Identificar los predictores clínicos y farmacoterapéuticos asociados a los niveles de severidad de las reacciones adversas (RAM) e interacciones medicamentosas (IM) en pacientes hospitalizados post accidente cerebrovascular. Métodos Estudio analítico, predictivo y transversal mediante el modelo de regresión lineal múltiple. Los niveles de severidad de las potenciales reacciones adversas e interacciones medicamentosas se evaluaron mediante Drugs.com. Resultados De la evaluación de 992 prescripciones médicas de 55 (56,7%) pacientes mujeres y 42 (43,3%) varones post accidente cerebrovascular isquémico 62 (63,9%) y hemorrágico 35 (36,1%), se identificó un total de 11 790±46,8 potenciales reacciones adversas y 1 034±9,8 interacciones medicamentosas. La hipertensión arterial se asoció a las reacciones adversas graves y moderadas, en tanto que la neumonía intrahospitalaria y alcalosis metabólica a reacciones adversas leves y moderadas. La alcalosis metabólica se asoció a las interacciones medicamentosas moderadas y leves. Los predictores farmacoterapéuticos como la prescripción en polifarmacia y el uso de antibióticos se relacionaron con reacciones adversas graves, moderadas y leves; los antidiabéticos se relacionaron con interacciones medicamentosas graves, moderadas y los fármacos para terapia cardiaca con interacciones medicamentosas leves. Conclusiones Las variables clínicas como factores de riesgo cardiovascular, presencia de comorbilidades que exacerban las enfermedades crónicas no trasmisibles, los signos y síntomas de alarma, el mayor tiempo de estancia hospitalaria y la prescripción en polifarmacia fueron predictores de mayor frecuencia de reacciones adversas e interacciones medicamentosas graves y moderadas que requieren especial vigilancia y estudio individualizado.

Objective To identify clinical and pharmacotherapeutic predictors associated with severity levels of adverse reactions and drug-drug interactions in post-stroke hospita-lized patients. Methods Analytic, predictive, cross-sectional study using multiple linear regression modeling. Severity levels of potential adverse reactions and drug-drug interactions were assessed using Drugs.com. Results From the evaluation of 992 medical prescriptions of 55 (56.7%) female and 42 (43.3%) male patients post ischemic stroke 62(63.9%) and hemorrhagic stroke 35 (36.1%); a total of 11 790±46.8 potential adverse reactions and 1 034±9.8 drug-drug interactions were identified; arterial hypertension was associated with severe and moderate adverse reactions; while in-hospital pneumonia and metabolic alkalosis with mild and moderate adverse reactions. While metabolic alkalosis was associated with moderate and mild drug-drug interactions. Pharmacotherapeutic predictors such as polypharmacy prescription and antibiotic use were related to moderate and mild severe adverse reactions; antidiabetic drugs were related to moderate and severe drug-drug interactions and cardiac therapy drugs were related to mild drug-drug interactions. Conclusions Clinical variables such as cardiovascular risk factors, presence of comorbidities that exacerbate chronic noncommunicable diseases, alarm signs and symptoms, longer hospital stay, as well as polypharmacy prescriptions, were predictors of a higher frequency of severe and moderate adverse reactions and drug-drug interactions, which require special vigilance and individualized study.

A comparative study of knowledge, attitude, and practice of drug-drug interactions among interns and nurses in a tertiary care hospital

Background: Increasing use of drugs has led to drug-drug interactions (DDIs) which necessitate their awareness among the health-care providers to reduce the hospital admissions due to their adverse drug reactions. Aim and Objectives: This study aims to assess and compare the knowledge, attitude, and practice (KAP) of DDIs among interns and nurses and to evaluate the impact of an educational program with a pre-and post-test questionnaire. Materials and Methods: An educational program about DDIs was conducted for the interns and nurses to evaluate their KAP by a pre-test and post-test pre-verified 20-point questionnaire about DDI. Results: There was a statistical significant difference (P < 0.05) in gender (females: Males = 77:16) among the interns and nurses and their mean age was 23 ± 0.87 years and 21.3 ± 0.83 years, respectively. Both the groups fared well in post-test compared to pre-test in the knowledge (questions=7), attitude (questions=5), and practice (questions=8) domain which was statistically significant. On comparing the post-test scores, both the groups showed no difference statistically (P > 0.05) in the knowledge and attitude domain, while the nurses group showed more improved mean score than interns in terms of practice of DDI. Conclusion: The educational program about DDIs was effective among the interns and nurses with regard to their KAP assessment and they equally performed well. This implies that the awareness program about DDIs was successful among the interns and nurses who form the lower strata in delivering the health-care needs to the society.

Potential drug-drug interactions among patients with spontaneous intracerebral hemorrhage treated at the Neurological Intensive Care Unit: a single-center experience

Abstract Our aim was to determine the prevalence of potential drug-drug interactions (pDDIs) and to identify relevant factors associated with the occurrence of the most dangerous or contraindicated pDDIs (pCDDIs) in hospitalized patients with spontaneous intracerebral hemorrhage (sICH). A retrospective cross-sectional study was performed enrolling all consecutive patients with sICH treated at the Neurological Intensive Care Unit, Clinical Center in Kragujevac, Serbia, during the three-year period (2012-2014). The inclusion criteria encompassed patients aged 18 years and over, those diagnosed with ICH, and those prescribed at least two drugs during hospitalization, while we did not include patients whose hospitalization lasted less than 7 days, those who were diagnosed with other neurological diseases and patients with incomplete medical files. For each day of hospitalization, the online checker Micromedex® software was used to identify pDDIs and classify them according to severity. A total of 110 participants were analysed. A high prevalence of pDDIs (98.2%) was observed. The median number of pDDIs regardless of severity, was 8.00 (IQR 4.75-13.00;1-30). The pairs of drugs involving cardiovascular medicines were the most commonly identified pDDIs. Twenty percent of the total number of participants was exposed to pCDDIs. The use of multiple drugs from different pharmacological-chemical subgroups and the prescribing of anticoagulant therapy significantly increase the chance of pCDDI (aOR with 95% CI 1.19 (1.05-1.35) and 7.40 (1.13-48.96), respectively). This study indicates a high prevalence of pDDIs and pCDDIs in patients with sICH. The use of anticoagulant therapy appears to be the only modifiable clinically relevant predictor of pCDDIs.

Risk factors for potential drug-drug interactions of statins in patients with acute coronary syndrome

Abstract The aim of our study was to assess risk factors for potential drug-drug interactions (pDDIs) of statins across different phases of treatment of acute coronary syndrome (ACS) patients: from the point of first medical contact to the coronary angiography (first phase), after coronary angiography to the last day of hospitalization (second phase) and at discharge from hospital (third phase). This was a post hoc analysis of the data collected during the retrospective observational cohort study conducted at the Clinic for Cardiology of the Clinical Centre Kragujevac, Serbia. Patients prescribed statins were identified from the original study population: 156, 240 and 236 patients for the first, second and third phases, respectively. At least one statin pDDI was present in 113 (72.4%), 161 (67.1%) and 139 (58.9%) patients in the first, second and third phases, respectively. Heart failure, arrhythmias after ACS, CRP, triglycerides, length of hospitalization, number of prescribed drugs, antiarrhythmic drugs, and clopidogrel seem to increase the risk of statin pDDIs in at least one treatment phase. Physicians should be vigilant to the possibility of statin pDDIs in ACS patients who have factors that may increase their rate.

Drug selection for simultaneous treatment of tuberculosis combined with hepatitis C virus infection / 中华肝脏病杂志

Clinically, patients with tuberculosis (TB) combined with hepatitis C virus (HCV) infection often require simultaneous treatment. Consequently, when anti-HCV and TB drugs are used in combination drug-drug interactions (DDIs), anti-TB drug-induced hepatotoxicity, and liver disease states need to be considered. This paper focuses on discussing the metabolic mechanisms of commonly used anti-TB and HCV drugs and the selection options of combined drugs, so as to provide rational drug use for TB patients combined with HCV infection.

Study Of Potential Drug Interactions Among Eight Major Departments-General Medicine, Orthopedics, Gynecology, Pulmonology, General Surgery, Psychiatry, Otolaryngology And Dermatology Of A Tertiary Care Teaching Hospital In Southern India

Objective: To identify frequency, type, severity and predictors of potential drug-drug interactions(pDDIs), potential drug-food interactions(pDFIs), potential drug-alcohol interactions(pDAIs) and potential drug-tobacco interactions(pDTIs) and most frequently interacting drug combination pairs in hospitalized patients from departments(depts) of General Medicine(GM), Orthopedic(Ortho), Gynecology(OBG), Pulmonology(Pulmo), General Surgery (GS), Psychiatry (Psych), Otolaryngology(ENT) and Dermatology (Derm) of study population. Methods: A Prospective Observational Study was conducted in eight major dept's of a tertiary care teaching hospital for a period of 6 mo. A sample size of 650 prescriptions reflecting admission no's for each department were used. Results: A total of 650 patients were included in the study. Among them, 282(43.4%) were males and 368(56.6%) were females. The mean age of the study population was 39.67±15.23. A total of 487 pDDIs, 734 pDFIs, 586 pDAIs and 159 pDTIs were found out of 650 hospitalized episodes. OBG showed the highest pDDIs and pDAIs. Highest pDFIs and pDTIs were seen in Pulmo. The majority of DDIs were minor, DFIs and DAIs were moderate and DTIs were of major in severity. Pharmacokinetic types of interactions were seen in the majority of the depts. Logistic regression analysis showed that Polypharmacy was associated with the occurrence of DIs. Most of the DIs repeated several times in particular depts and a list of these combinations was prepared. Conclusion: With the high occurrence of overall DIs and characteristic patterns of DIs combination pairs among different departments of the hospital, the presence of clinical pharmacists in hospitals can play a great role, especially in developing nations like India where their role in hospitalized settings is always controversial.

Prevalence of Side Effects, Drug Interaction among Patients Taking Statin in Turaif, Saudi Arabia

Background:Statins perceived to have favorable safety profile. Although many people on statin therapy do well but no drug is without potential for side effects. Awareness about risks as well as benefits of drugs is needed particularly drugs which are used on wide scale like statins because even uncommon side effects can have significant health impact. Objectives of the Study: To determine side effects occurrence among Saudi patients taking statins and to evaluate drug-drug interactions in Saudi patients taking statins.Methodology:Self administered cross sectional study conducted during a period of four months from October 2018 to January 2019 in Turaif general hospital, Saudi Arabia on random sample of 500 Saudi patients out of which 330 participants were included in the study which were taking different types of statins medication using self-administered questionnaire in Arabic language specially designed for the research purpose after obtaining verbal consent and the data analyzed by SPSS program.Results:A total of 330 patients; 128 (39%) females and 202 (61%) males—participated in the study. The majority 165 (50%) were in the age-group of 50 –59 years. Simvastatin was the most commonly used statin among study participants 136 (41%) followed by rosuvastatin114 (35%). Among the participants, there were some patients who take drugs which have drug interactions with statins; there were 64 (19%) take Amlodipine with simvastatin, 13 (4%) and 6 (2%) take esomeprazole and ompeprazole respectively with statins. Only 9 (3%) reported that they were advised by pharmacist to avoid grape fruit. Majority of participants 309 (94%) reported neck pain, difficulty in walking, frequently fatigue after starting on statin. Also majority of participants 320 (97%) suffer from muscle pain after starting statins medications. Conclusion:The percentage of statin related side effects in this study population is high especially myopathy. Also some patients in this study taking medications that have drug interaction with statins, Counseling to patient regarding statin therapy appear to be insufficient. So, this study indicate that there's a need for more efforts from the physicians and pharmacist to avoid prescribing or dispensing medication that have drug-drug interaction with statins and provide counseling to patients regarding their statin therapy

Prevalence, predictors and outcomes of potential drug-drug interactions in left ventricular failure: considerable factors for quality use of medicines

Hospitalized patients with left ventricular failure (LVF) are at high risk for potential drug-drug interactions (pDDIs) and its related adverse effects owing to multiple risk factors such as old age, comorbidities and polypharmacy. This cross-sectional study conducted in two tertiary care hospitals aim to identify frequency, levels and predictors of pDDIs in LVF patients. Data about patients' demographic, hospital stay, medication therapy, sign/symptoms and laboratory test results were collected for 385 patients with LVF. Micromedex Drug-Reax® was used to screen patients' medication profiles for pDDIs. Overall prevalence and severity-wise prevalence of pDDIs were identified. Chi-square test was performed for comparative analysis of various variables. Logistic regression was applied to determine the odds-ratios (OR) for predictors of pDDIs. The prevalence of pDDIs was 96.4% (n=371). Overall 335 drug-interacting pairs were detected, which were presented in a total of 2870 pDDIs. Majority of pDDIs were of major- (48.9%) and moderate-severity (47.5%). Logistic regression analysis shows significant association of >6 all types of pDDIs with >12 drugs as compared with <8 drugs (OR=16.5; p=<0.001). Likewise, there was a significant association of >4 major-pDDIs with men as compared with female (OR=1.9; p=0.007) and >12 drugs as compared with <8 drugs (OR=10.9; p=<0.001). Hypotension (n=57), impaired renal function (23) and increased blood pressure (22) were the most frequent adverse outcomes associated with pDDIs. This study shows high prevalence of pDDIs in LVF patients. Majority of pDDIs were of major- and moderate-severity. Male patients and those prescribed greater number of medicines were more exposed to major-pDDIs

Potential Drug-Drug Interactions In Heart Failure Patients

Objective: The aim of the present study was to assess the prevalence, risk rating and the severity of hazardous pDDIs (potential drug-drug interactions) in the prescribed pharmacotherapy in the hospital discharged heart failure (HF) patients, primarily with co-administered drugs with narrow therapeutic index (statins, anticoagulants, antithrombotic drugs). Methods: The prescriptions of chronic heart failure patients for one year (January-December 2014) were analyzed for pDDIs through Lexi-interact® software. DDIs belonging to the categories D (Consider therapy modification) and X (Avoid combination) and/or severity of drug interaction-major, were selected for the study. Results: After reviewing the medical records of 985 patients, 239 patients were selected based on the criteria mentioned above. The average number of prescription drugs at hospital discharge was 7.27 medications (±1.84 SD) per patient. The total number of pDDIs was 1483 or approximately 6.2 (±3.89 SD) pDDIs per patient. With respect to the risk rating, in categories D and X were detected 76 (5.12 %) and 2 (0.13 %) pDDI, respectively. The major pDDIs were 108 (7.28 %). Conclusion: HF patients are at high risk of pDDIs. Screening of prescriptions for pDDIs and monitoring of pharmacotherapy in terms of response and associated adverse drug events will contribute to patient safety.

Current trends in drug metabolism and pharmacokinetics

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.

Evaluation of Antiplasmodial Activity and Safety of Flower Extracts of Chrysanthemum cinerariaefolium, Singly and in Combination with Chloroquine, Lumefantrine and Piperaquine

Objective: To evaluate the antiplasmodial activity and safety of organic and aqueous flower extracts of Chrysanthemum cinerariaefolium from Kenya, singly and in combination with chloroquine, lumefantrine and piperaquine. Methodology: Antiplasmodial activity of organic and aqueous flower extracts of C. cinerariaefolium was assessed in vitro by serial micro-dilution assay technique against Plasmodium falciparum, and in vivo using the 4-day suppressive test as well as the established infection test against P. berghei ANKA in mice. To determine the safety of the extracts, cytotoxicity evaluation of extracts against Vero E6 cells and acute toxicity studies in mice were also done. Results: In vitro antiplasmodial assays showed that methanolic extract of C. cinerariaefolium flowers was active, petroleum ether extract was moderately active, while the aqueous extract was inactive. Methanolic extract combined with chloroquine (CQ) against CQ-sensitive (3D7) and CQ-resistant (W2) P. falciparum showed marked synergy. Both methanol and aqueous extracts (1000mg/kg) showed chemosuppression of >45% (P<0.05) in both 4-day suppression test and established infection test against P. berghei ANKA in mice. Lumefantrine (LU) or piperaquine (PQ) combined with either methanol or aqueous extracts showed chemosuppression of >63% (P<0.05) against LU-resistant and PQ-resistant P. berghei ANKA strains, indicating synergistic interactions. Methanolic and aqueous flower extracts of C. cinerariaefolium had no cytotoxic effect on Vero E6 cells and no overt signs of toxicity in mice. Conclusion: The findings showed that C. cinerariaefolium flower extracts are safe in mammalian systems, have antiplasmodial activity and have potentiation effect of conventional antimalarials. There is need therefore to further explore the plant’s bioactive molecules which may serve as template for development of novel, effective and affordable antimalarial agents for management of malaria.

Effects of Dendrobium huoshanense on expressions and activities of hepatic microsomal cytochrome P450s in mice / 中国中药杂志

This study was carried out to investigate the effect of oral administration of Dendrobium huoshanense on the expressions and activities of hepatic microsomal cytochrome P450s in mice, and to provide a reference for the evaluation of drug-drug interactions between D. huoshanense and clinical drugs. The C57BL/6 mice were randomly divided into blank control group, D. huoshanense low dose group (crude drug 1.25 g·kg⁻¹), D. huoshanense high dose group (crude drug 7.5 g·kg⁻¹), and phenobarbital positive control group (0.08 g·kg⁻¹). Each group was intragastrically administered with drugs for 2 weeks. The mice were sacrificed and their liver microsomes were prepared. The expressions of major subtypes of P450 enzyme were determined by Western blot and the probe drugs were used to detect the enzyme activities of P450 subtypes with protein expression changes. Western blot analysis showed that the protein expressions of CYP1A1, CYP1A2 and CYP2B in liver tissues were up-regulated in D. huoshanense-treated group. In vitro enzyme activity tests showed that there were no significant difference in metabolism of 7-ethoxyresorufin (a probe drug for CYP1A1) and bupropion (a probe drug for CYP2B) between D. huoshanense group and control group. The metabolism of phenacetin (a probe drug for CYP1A2) showed a statistical difference in rate Vmax, and it was significantly increased by approximately 20% in D. huoshanense group as compared with the blank control group, and the clearance CLint in treated group was also increased by about 32%. Therefore, oral administration of D. huoshanense had no effects on the activities of most hepatic P450 enzymes in mice, with no drug-drug interaction related to the P450 enzyme system in most clinical drugs theoretically. However, oral administration of D. huoshanense may accelerate the metabolism of CYP1A2-catalyzed drugs, which needs to be considered in clinical practice.

Advances in Metabolizing Enzymes and Transporters Mediated Capsaicin-Drug Interaction / 中国药学杂志

With the continuously clinical study of capsaicin, capsaicin-drug interaction has become increasingly prominent. In recent years, the studies indicate that capsaicin shows a significant inducing or inhibitory effect on a variety of drug metabolism enzymes and transporters, thereby leading to the occurrence of complex drug interactions and affecting the other drugs in vivo process. In this paper, the modulation effect of capsaicin on drug metabolizing enzymes and transporters by reviewing the relevant research at home and abroad in recent years were summarized, and the drug-drug interactions associated with capsaicin in order to provide theoretical guidance for clinical rational drug use were explored. Furthermore, complex drug-drug interaction studies can be provided with prior examples.

Clinical issues in the diagnosis and treatment of tuberculosis patients with positive antibody to hepatitis C virus / 临床肝胆病杂志

Tuberculosis patients with positive antibody to hepatitis C virus (TB-HCV patients) are often seen in clinical practice, and these TB-HCV patients include those with HCV infection. That makes the clinical management and diagnosis/treatment of TB-HCV difficult. This article introduces the prevalence of TB-HCV around the world, and analyzes the potential issues in the diagnosis and treatment of TB-HCV patients, such as drug-drug interactions, drug-induced liver injury, HCV reactivation, and TB reactivation. Through this review, it is recommended that the management should be strengthened and the appropriate therapeutic regimen should be selected in the diagnosis and treatment of TB-HCV patients.

Evaluation of hypoglycemic drug-drug interactions by software / 药学实践杂志

Objective To evaluate and analyze the drug-drug interactions(DDI)of different antidiabetic drugs.Methods DDI database Lexi-InteractionTMwas used to evaluate DDI for 28 commonly used antidiabetic medications(including insulin and 27 non-insulin preparations).Results 882 DDIs were identified for 28 drugs.Category C was the top rated DDI(69.8%). Category C,D,X were accounted for 91.2% of the total DDI.28 medication combinations belonged to category X,which should be avoided to use together.Sulfonylureas had the most DDI,followed by metformin.Alpha-glucosidase inhibitors had least DDI.Conclusion Hypoglycemic drugs with less DDI,such as α-glycosidase inhibitors,glucagon-likepeptide1(GLP-1)an-alogs and sodium-dependent glucose transporters 2 inhibitor(SGLT2i)should be considered with high priority for patients tak-ing multiple antidiabetic medications,elderly patients and patients with liver-kidney dysfunction.

Sofosbuvir and Daclatasvir in Mono-and HIV-coinfected Patients with Recurrent Hepatitis C After Liver Transplant

Abstract: Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. Material and methods. We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. Results. Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. Conclusion. The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.

Prevalence of potential drug-drug interactions in the intensive care unit of a Brazilian teaching hospital

Abstract Patients in intensive care unit are prescribed large numbers of drugs, highlighting the need to study potential Drug-Drug Interactions in this environment. The aim of this study was to delineate the prevalence and risk of potential drug-drug interactions between medications administered to patients in an ICU. This cross-sectional observational study was conducted during 12 months, in an adult ICU of a teaching hospital. Inclusion criteria were: prescriptions with 2 or more drugs of patients admitted to the ICU for > 24 hours and age of ≥18 years. Potential Drug-Drug Interactions were quantified and classified through MicromedexTM database. The 369 prescriptions included in this study had 205 different drugs, with an average of 13.04 ± 4.26 (mean ± standard deviation) drugs per prescription. Potential Drug-Drug Interactions were identified in 89% of these, with an average of 5.00 ± 5.06 interactions per prescription. Of the 405 different pairs of potentially interacting drugs identified, moderate and major interactions were present in 74% and 67% of prescriptions, respectively. The most prevalent interaction was between dipyrone and enoxaparin (35.8%), though its clinical occurrence was not observed in this study. The number of potential Drug-Drug Interactions showed significant positive correlations with the length of stay in the intensive care unit, and with the number of prescribed drugs. Acknowledging the high potential for Drug-Drug Interactions in the ICU represents an important step toward improving patient safety and best therapy results.