DIPEPTIDYL PEPTIDASE 4 (DPP-4) INHIBITORS FOR THE TREATMENT OF TYPE 2 DIABETES MELLITUS

ABSTRACT Diabetes mellitus (DM) is a chronic disease which caused around 1.5 million deaths in 2012. Type 2 diabetes mellitus (T2DM) accounts for 90% of DM worldwide. The prevalence of T2DM is increasing due to obesity. Clinical guidelines recommend the use of metformin as the first-line treatment, followed by the addition of 1 or 2 oral antidiabetic drugs (OADs), such as sulphonylurea (SU), an alpha-glucosidase inhibitor, or thiazolidinediones (TZDs). Recently, newer agents such as dipeptidyl peptidase 4 (DPP-4) inhibitors have been added to those treatment algorithms. The DPP-4 inhibitor is a class of OAD that inhibits the DPP-4 enzyme. Sitagliptin, saxagliptin, vildagliptin and linagliptin are DPP-4 inhibitors available for the treatment of T2DM in Indonesia and many other countries. The DPP-4 inhibitors have similar glycemic efficacy. However, they produce a moderate improvement in glycated hemoglobin (A1C). There are limited numbers of head-to-head trials of DPP-4 inhibitors. In addition, there are no data on the long-term DPP-4 inhibitors use safety (more than two years), mortality, diabetic complications, or health-related quality of life. Although DPP-inhibitors are not used as initial treatment for a majority of patients with T2DM, DPP-4 inhibitors can be used as add-on therapy in T2DM patients who are intolerant to, have contraindications for, or uncontrolled with the use of metformin, SU, or TZDs. The exact role of DPP-4 inhibitors among several other agents to manage T2DM is not clear. There are only a small number of long-term studies on DPP-4 inhibitors assessing the glycemic decrease efficacy, important clinical outcomes (cardiovascular events, mortality), or safety. In patients with chronic renal failure considered to use DPP-4 inhibitors, linagliptin can be recommended. There are inadequate data to assess the effect of DPP-4 inhibitors on the occurrence of acute pancreatitis. Overall, DPP-4 inhibitors are well-tolerated

POTENTIAL DRUG INTERACTIONS IN HYPERTENSIVE PATIENTS IN LIWA DISTRICT HOSPITAL, LAMPUNG BARAT, INDONESIA

Objective: Patients with hypertension often suffer from other comorbidities, resulting in prescriptions of multiple drugs to treat the conditions. Multiple drug treatment is potentially associated with drug interactions. This aim of the study was to assess potential drug interactions in hypertensive patients in Liwa District Hospital.Methods: The design of the study was cross-sectional. The prescriptions for in-patients with essential hypertension in the Internal Medicine Unit in Liwa District Hospital during April-December 2012 were collected. Potential drug interactions were analyzed with the Drug Interaction Facts version 4.0, and classified into minor, significant, and serious.Results: A total of 60 hypertensive patients were included. They were prescribed 265 prescriptions, with a median total of 6 (range 1-21) drugs prescribed per prescription. There were 1616 potential drug interactions, with 6 (1-31) potential interactions per prescription. Most interactions (75.6%) were classified as significant. Serious potential interactions were most common in the combinations of diltiazem-amlodipine and spironolactone-potassium chloride, while significant potential interaction may occur most often with the combinations of calcium chloride-amlodipine and bisoprolol-amlodipine.Conclusion: Numerous potential drug interactions might occur in hypertensive patients, and most interactions were significant in severity. The largest proportion of the interactions occurred between antihypertensive agents and other drugs.Â

Improving the use of antibiotics in primary health centres through a problem-based pharmacotherapy training approach

ABSTRACT Iwan Dwiprahasto & Erna Kristin - Improving the use of antibiotics in primary health centres through a problem-based pharmacotherapy training approach Background: Inappropriate use of antibiotics in the treatment of common diseases such as acute respiratory infection (ARI) and diarrhoea has been the major health problems in primary health centres (PHCs). Beside increasing the risk of adverse event, excessive use of antibiotics has also led to bacterial resistance worldwide. Objective: To improve the quality of prescribing of Primary Health Centers\u27 (PHCs) physicians and paramedics particularly in the treatment of ARI and diarrhoea. Design: Prospective intervention study with control group involving 113 PHCs\u27 physicians in both arms. Thirteen districts were randomly selected for study area, in which intervention was carried out in 8 districts while 5 other districts as control group. A systematic problem-based approach of 3 days training were carried out in the intervention group using 3 sets of modules, followed by self monitoring & regular visit & feedback by a Training Team. Evaluation on prescribing was carried out 3 times, i.e at the 6th , 12th, &18th month after intervention. Results: More than 17 thousands and 8600 prescriptions for ARI and diarrhoea were collected during the study. There was a significant reduction in the use of antibiotics for ARI in the intervention group from 92.3 before the study, to 67.4, 52.8 and 39.5%, 6, 12, & 18 month after the study (p0.05). There has been significant antibiotics prescribing shift toward more rational choice in the intervention group 18 months after the study. Conclusions: A systematic problem-based pharmacotherapy training followed by self monitoring & regular visit & feedback significantly improved antibiotic prescribing for ARI and diarrhoea. Key words: antibiotics - prescribing - problem-based pharmacotherapy training - acute respiratory infection - diarrhoe

Mucolitic Ambroxol Versus Hypertonic Saline Nebulizer Induction: For Increasing Sputum Volume And Finding Acid-Fast Bacilli

Introduction: Tuberculosis, a major killer disease in the community, was caused by Mycobacterium tuberculosis. According to WHO (2006), pulmonary tuberculosis cases in Indonesia was third ranked in the world. Prevalence of pulmonary tuberculosis in Eastern Indonesia was higher than in Java and Bali, but the findings of positive smear was lowest. AFB discovery will be decreased because of the poor quality and quantity of sputum.The useful of mucolitic ambroxol or hypertonic saline nebulizer induction will be to increase quality and quantity of sputum smear.Objectives: The aim of this study was to determine and to compare the effectiveness of ambroxol and use a hypertonic saline induction on new suspected pulmonary tuberculosis patients to increase sputum volume and to find AFB.Methods: 76 new suspected pulmonary tuberculosis patients were divided into 2 groups with doubleblind and open-label simple randomsampling RCT (Randomized Controlled ClinicalTrial-Parallel design) study.The sputum induction using ambroxol or 3%hypertonic saline solution.The primary and secondary outcome were increasing sputum volume and finding AFB by Ziehl-Neelsen staining to calculate the AFB count per 100 fields of view. Non parametric statistical analysis and percentage of success.Results: All patients can produce sputum. Only one patient ambroxol group can’t produce it.The quality and quantity of sputum hypertonic saline induction volume better than ambroxol. AFB finding increaseboth groups, but no significant difference. AFB finding increase 26.47%(9/34)with ambroxol and 27.78% (10/36)with hypertonic saline induction compared than previous negative smear.Conclusions: Significant differences increase sputumvolume hypertonic saline induction compared than ambroxol.No significant difference AFB finding improvement hypertonic saline induction compared for ambroxol. Finding AFB increase 26.47% with ambroxol and 27.78% with hypertonic saline induction compared previous negative smear.Keywords: Tuberculosis, Ambroxol, Nebulizer induction, Sputum volume, AF

DECREASE OF LIVER FUNCTION AFTER TREATMENT OF ANTITUBERCULOSIS DRUGS IN TUBERCULOSIS PATIENTS WITH MALNUTRITION AND ALCOHOL CONSUMPTION

Objective: To evaluate the decrease of liver function after treatment of antituberculosis drugs-fixed doses combination (ATD-FDC) category 1 in tuberculosis patients with malnutrition and alcohol consumption.Methods: This was an experimental study, with a quasi-experimental pretest and posttest design, to evaluate the increase in SGPT in pulmonary TB patients with malnutrition, treated with ATD-FDC for 8 w. Inclusion criteria were: pulmonary TB patients, aged ≥ 18 y old, who would receive ATD-FDC category 1 treatment, did not have an increase in SGPT level at the beginning of the treatment and were willing to join the study. This study was conducted in all community health centers in Kupang, Indonesia.Results: The result of this study showed that percentage of SGPT level is increased after treatment of ATD-FDC compared with before treatment in TB patient with malnutrition compared with TB patients without malnutrition (135.1% vs. 54.7%; p<0.001). The difference of SGPT level in TB patients ≥40 y versus<40 y was 15.5 IU/l versus 9.1 IU/l (p<0.05). The difference of SGPT level in TB patient ≥40 y with routine alcohol consumption habit compared with non-routine alcohol consumption was 29.3 IU/l vs. 12.8 IU/l (p<0.01).Conclusion: Pulmonary TB patients with malnutrition had a larger decrease in liver function after treatment with ATD-FDC category 1 for 8 w, compared to those without malnutrition. Routine alcohol consumption had an effect on the increase in SGPT level in older patients.Keywords: ATD-FDC-malnutrition-alcohol consumption

Combination treatment for type 2 diabetes mellitus (T2DM) : dipeptidyl peptidase-4 inhibitors (DPP-4) and metformin

Using the concept of inhibition of dipeptidyl peptidase-4 (DPP-4) as a new treatment for type 2 diabetes mellitus (T2DM) is based on the inhibition of bioactive peptide inactivation process. Most clinical trials on DPP-4 inhibition are based on vildagliptin, sitagliptin, saxagliptin, and linagliptin. The drugs may improve glycemic control when they are given as a combination with other oral hyperglycemic agents or when they are given to patients who received metformin and still had inadequate glycemic control. Studies showed that vildagliptin was well-tolerated if it was given as add-on treatment to metformin for 24 weeks duration. In addition, vildagliptin showed significant clinical improvement proven by the associated decrease in HbA1c and fasting glucose levels. Sitagliptin in initial combination therapy with metformin decreased HbA1c level by 2.1% after 24 weeks of treatment. It was reported that DPP-4 inhibitor saxagliptin increased glycemic control when it was added to metformin. The study included 743 patients with an average HbA1c level of 8.0% when they were treated with metformin alone. After 24 weeks of treatment, saxagliptin decreased HbA1c level by 0.7%. A multicenter, randomized, placebo-controlled, double-blind, parallel-group study examined the efficacy and tolerability of linagliptin as treatment adjunctive to metformin in patients T2DM. The primary end point was changed in HbA1c from baseline to 24 weeks of treatment. The mean adjusted change from baseline in HbA1c in the linagliptin group was 0.49% compared with an increase of 0.15% in the placebo group, with 26% and 9% of participants in the linagliptin and placebo groups, respectively, achieving an HbA1c 7.0% at 24 weeks. The combination of DPP-4 inhibitors and metformin has been shown to be well-tolerated with a very low risk of hypoglycemia. Therefore, DPP-4 inhibitors and metformin combination is an efficient, safe, and well-tolerated therapy for T2DM

Pengaruh pemberian rifampisin terhadap profil farmakokinetika glipizid pada orang sehat

Luciana Kuswibawati, Iwan Dwiprahasto, Erna Kristin - The effect of rifampicin administration on the pharmacokinetic profile of glipizid in normal subjects Background: The use of antituberculosis drugs among diabetic patients is not infrequent. Among these, glipizide is one of the widely used antidiabetic drugs. The use of this second generation sulfonylurea in combination with rifampicin is common.Rifampicin is known as enzyme inductor that can influence other drugs metabolism used in combination. Objective: To investigate the effect of rifampicin pretreatment on the pharmacokinetic parameters of glipizide among 12 Indonesian healthy volunteers. Methods: Using randomized crossover design, volunteers were divided into two groups, i.e control and rifampicin pretreatment groups. Before starting the experiment, the pretreatment group was given 450 mg of rifampicin orally which should be taken daily for 7 days. Subsequently, a single dose of 5 mg glipizide was ingested to control and the pretreatment group as well. After oral administration of single dose of 5 mg glipizide, the samples were collected serially at 00.50.7511.522.534579 and 12 hours to analyze blood glipizide level. High Pert ormace Liquid Chromatography (HPLC) method was used to analyze glipizide pharmacokinetic profile. From the data obtained, the pharmacokinetic parameters were calculated using noncompartment model. Results: The results showed that there were no significant change in the value of Tmax, Cmax, Ka, significant increases clearence (CI) 101.8% and elimination rate constant (Kel) 116.7% of the rifampicin pretreatment group. The elimination half life (T1/2) were shortened 39.5% from 3.8 to 2.3 hours (

The influence of acetylation status of tuberculosis patients on the isoniazid serum concentrations and sputum conversion after intensive phase therapy

Isoniazid (INH), one of the major antituberculosis drugs, is metabolized by acetylation. Previously study proved the significant differences of serum INH concentration between subject with fast and slow acetylation status. However, the correlation of acetylation status with treatment outcome after fixed-dose combination antituberculosis therapy (FDC-ATT) was not explained. The aim of this study was to evaluate the influence of acetylation status on the treatment outcome and the serum INH concentrations in the adult tuberculosis patients underwent FDC-ATT. A cross sectional study was carried out on 31 tuberculosis patients. Acetylation status was measured by spectrophotometer and serum INH concentration was measured by high performance liquid chromatography (HPLC). Sputum conversion assay was conducted by Ziehl Nelsen method. t-Test, chi square, Mann-Whitney, and Fisherman were used to analyze the data. The proportion of the fast acetylator was 61.3%, whereas the slow acetylator was 38.7%. The proportion of success and failure sputum conversion were 83.9% and 16.1%, respectively. The mean serum INH concentration in the fast acetylator groups (1.52 ± 0.15 μg/mL) was significantly lower than that in the slow acetylator groups (3.84 ± 0.35 μg/mL). The failure conversion risk of the fast acetylator group was about two folds higher than the slow acetylator group, although it was not significantly different (RR=2.53; 95% CI=0.32-20.00; p>0.05). Moreover, the mean serum INH concentration in success (2.46 ± 0.31 μg/mL) and failure (1.89 ± 0.20 μg/mL) sputum conversion was not significantly different (p>0.05). In conclusion, the acetylation status does not influence the sputum conversion in adult tuberculosis patients after FDC-ATT although the serum INH concentration on slow acetylation status is higher than that fast acetylation status.

EFFECTIVENESS OF TICAGRELOR COMPARED TO CLOPIDOGREL IN REDUCING THE RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH CORONARY HEART DISEASE AFTER PERCUTANEOUS CORONARY INTERVENTION

Objective: Antiplatelet therapy is recommended in patients with coronary heart disease (CHD) who had the percutaneous coronary intervention (PCI) procedure to reduce major adverse cardiovascular events (MACE). There has been a lack of population-based studies that showed the superior effectiveness of ticagrelor over clopidogrel and similar studies have not been conducted in Indonesia yet. The aim of the study was to investigate the effectiveness of ticagrelor compared to clopidogrel in reducing the risk of MACE in patients with CHD after PCI. Methods: A retrospective cohort study with 1-year follow-up was conducted. 361 patients consisted of 111 patients with ticagrelor exposure and 250 patients with clopidogrel exposure. The primary outcome was MACE, defined as a composite of repeat revascularization, myocardial infarction, or all-cause death. The association between antiplatelet exposure and the MACE was analyzed with Cox proportional hazard regression, adjusted for sex, age, comorbid, PCI procedures and concomitant therapy. Results: MACE occurred in 22.7% of the subjects. Clopidogrel had a significantly higher risk of MACE compared with ticagrelor (28.8%, vs 9.0%, hazard ratio (HR): 1.96 (95% CI 1.01 to 3.81, p=0.047). There were no significant differences in risk of repeat revascularization (20.40% vs 5.40%, HR: 2.32, 95% CI 0.99 to 5.42, p = 0.05), myocardial infarction (11.60% vs 3.60%, HR: 2.08, 95% CI, 0.73 to 5.93, p = 0.17), and death (1.60% vs 1.80%, HR: 0.77, 95% CI, 0.14 to 4.25, p = 0.77). Conclusion: Clopidogrel had a higher risk of MACE compared to clopidogrel in patients with CHD after PCI, but there were no significant differences in the risk of repeat revascularization, myocardial infarction, and all-cause death.Â&nbsp