Indonesian Journal of Pharmacy
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Utilization of Psychotropic Medications and Polypharmacy Among Adults in Jazan Region, Saudi Arabia
Full text linkGlobally, there has been a surge in the prevalence of mental health disorders, not excluding Saudi Arabia. The availability of newer psychotropic medications has led to increased prescribing and polypharmacy. In Saudi Arabia, exploration of the knowledge gap between the outpatient use of psychotropic medications and the extent of polypharmacy has been scarce in the literature. This study evaluated the prescription pattern of psychotropic medications and the prevalence of psychotropic polypharmacy among adult patients with behavioral/mental illnesses. The study was conducted in the psychiatric outpatient clinics of five hospitals in Jazan Region of Saudi Arabia. A retrospective cross-sectional study was conducted with a non-random sample of adults with behavioral/mental illnesses. Psychotropic polypharmacy was the presence of ≥2 psychotropic medication prescriptions. We conducted multivariable logistic regression models to examine the factors associated with psychotropic polypharmacy. A total of 3.052 adults with a behavioral/mental illness were included in the study. Of these, 74.6% had antidepressant prescriptions. The second most prescribed drug class was antipsychotics (51.9%). Furthermore, 65.3% had psychotropic polypharmacy, and 48.2% had interclass psychotropic polypharmacy. Adults with anxiety and other mood disorders were less likely to engage in psychotropic polypharmacy and interclass polypharmacy use than those with depression. However, adults with schizophrenia (adjusted odds ratio [AOR]: 1.91; p<0.001) were more likely to engage in interclass polypharmacy use than those with depression. Adults with behavioral/mental illnesses in Jazan Region of Saudi Arabia have high rates of antidepressants and antipsychotics use. Additionally, psychotropic polypharmacy is a common prescribing practice, and further evaluation of the safety profile of these combinations is warranted
Development and Validation of Montelukast with Grape/Licorice Juices and its Application to Pharmacokinetic Studies by LC/MS
Full text linkA simple, rapid and sensitive simultaneous method for validation and determination of Montelukast in rat plasma in the presence of grape and licorice juices has been done by using High Performance Liquid Chromatography–Mass Spectrometry (HPLC/MS). A mixture of (77.5 % methanol, 22.5 % of 0.2% FA in water) was used as a mobile phase, ACE 5 C8 column (50 X 2.1 mm, 5μ), and a flow rate of 0.1 ml/min were used, the auto-sampler injection volume was 5 microliters, and candesartan was used as an internal standard. According to the result obtained, the precision of predicted measurements for Montelukast was good (mean CV % 0.05) of grape on Montelukast Cmax (163.492 ng/ml ±113.27). Neither licorice gives significant decrease in the Montelukast Cmax (143.861ng/ml ±54.52), its only delay the average Montelukast Cmax to half an hour. Even for the AUC, there were no significant difference between Montelukast alone and Montelukast with grape, and Montelukast with licorice (P>0.05). The kinetic data shows that Montelukast plasma level was the same with both combination of Montelukast and grape, and Montelukast and licorice
Bioassay Guided Fractionation of Marine Streptomyces sp. GMY01 and Antiplasmodial Assay using Microscopic and Flow Cytometry Method
Full text linkGenome mining study showed that marine-derived Streptomyces sp. GMY01 is a potential actinobacteria with abundant of secondary metabolite and anticancer activity. The study aimed to evaluate bioassay guided fractionation for antiplasmodial screening of GMY01 extract and to predict compound on active fractions. Ethyl acetate fraction was obtained from 11 days fermentation product of GMY01 and then it was fractionated using n-hexane and methanol solvent. Refractionated was applied using flash chromatography and column chromatography. Antiplasmodial assay was performed on Plasmodium falciparum FCR3 by microscopic method using thin blood smear + Giemsa stain, and flow cytometry method using SYBR Green I stain. Toxicity assay was performed on Vero cells line. Main constituent of active fraction was analyzed using LCMS/MS. The result of the study showed that ethyl acetate-methanol fraction has high antiplasmodial activity (IC50=3.96 µg/mL) with very low toxicity on Vero cells (IC50=30,072 µg/mL). Bioassay guided fractionation resulted F4.7 as highest Plasmodium inhibition (94.3% at 5 µg/mL) and was confirmed by microscopic and flow cytometry assay. Main constituent analysis showed C10H13NO (163.09971 Da) as mayor compound and predicted as nonribosomal polyketide synthetase (NRPS) secondary metabolite
Eleutherine palmifolia (L.) Merr. Extract Increases The Crypts and Caspase-3 Expression in Colitis-Associated Colon Cancer Model
Full text linkIt is known that Eleutherine palmifolia (L.) Merr contains flavonoid and polyphenol as bioactive compounds that have the ability as chemopreventive agents. This study aims to examine the effect of Eleutherine palmifolia (L.) Merr extract (EPE) on colon histopathology and the enhancement of caspase-3 expression in BALB/c mice of colitis-associated colon cancer (CAC) model. Thirty Balb/c female mice were used in this study and were divided into six groups. Five mice in one group were normal or negative control (given phosphate-buffered saline), and twenty-five mice were induced intraperitoneally with 10 mg/kg BW AOM (Azoxymethane), and it was followed by the administration of 5% DSS (Dextran Sodium Sulfate) every two weeks for 20 weeks. At the sixth week, one mice in each group was sacrificed for the Fecal Occult Bold Test (FOBT) and serum amyloid α (SAA) test to ensure that CAC was indeed formed. The administration of EPE with varying doses was started from the eighth week and was continued until the 21st week. The length of the colonic crypt was measured through histology appearance using Hematoxylin-eosin (HE) staining while the immunohistochemical method was used to observe apoptotic activity through the enhancement of caspase-3 expression. The results showed that the increase in EPE dosage also increased the crypt colon length compared to the positive control group. The administration of 1.00 mg/20gBW EPE significantly increased cell apoptosis which can be observed through caspase-3 expression compared to the positive control group (p<0.05). Based on these data, the extract of EPE can be developed as phytotherapy for chemopreventive.
 
Antiplasmodial Activity of The Low Molecular Weight Compounds from Streptomyces sp. GMR22
Full text linkLow molecular weight (LMW) antiplasmodial compounds isolated from bacteria, particularly Streptomyces have not been widely reported. This study aimed to identify LMW compounds from Streptomyces sp. GMR22 as antiplasmodial. Isolation of the LMW compounds from the supernatant of fermentation culture using solvent of n-hexane:ethylacetate (EtOAc) (85:15v/v)and identified using gas chromatography-mass spectrometry (GC-MS). Antiplasmodial assay of n-hexane:EtOAc extract was carried out in vitro against P. falciparum (3D7). Parasitemia percentage obtained through microscopic observations and 50% inhibitory concentration (IC50) obtained through probit analysis. The antiplasmodial confirmation test was done by flow cytometry using SYBR Green I for Plasmodium DNA and anti-human CD235a for erythrocytes. The LMW compounds were investigated using SwissADME for drug-likeness. n-Hexane:EtOAc extract contained 21 LMW compounds from alcohol, hydrocarbon, ester, aromatic/diester, diester, fatty acid, and triester classes, which possessed moderate antiplasmodial activity with an IC50 value of 38.61 ± 19.06 µg/mL. Confirmation by flow cytometry analysis showed that the extract at 50 µg/mL exhibited antiplasmodial activity based on a decreased Plasmodium DNA intensity as compared to the control group. The result of drug-likeness screening obtained that 3 LMW compounds were drug-likeness, namely phenylethyl alcohol, ethyl citrate, and di-n-butyl phthalate. Streptomyces sp. GMR22 produced LMW compounds as antiplasmodial, and further study was needed for identification of antiplasmodial active compounds
Zingiber Officinale Var. Rubrum Extract Increases The Cytotoxic Activity Of 5-Fluorouracil In Colon Adenocarcinoma Widr Cells
Full text linkOne of the main chemotherapy agents for colon cancer is 5-fluorouracil (5-FU). However, the effectiveness of 5-FU decreased; therefore, co-chemotherapy with another agent is needed to enhance the activity. This study aims to determine the effect of red ginger extract as a co-chemotherapy agent with 5-FU on WiDr colon adenocarcinoma cells. We investigated the cytotoxic activity of the ethanolic extract of rhizome red ginger and combination with 5-fluorouracil (5-FU) in WiDr human colorectal cancer cell line. Red ginger extract was extracted by using 96% ethanol. Cytotoxic assay of red ginger extract and 5-FU was performed using MTT assay for 24 and 48 hours. Treatment of 5-FU in WiDr cells for 48 hours showed an IC50 value of 130 µg/mL, while no IC50 value was obtained for the 24 hours treatment. Treatment of red ginger extract with an incubation time of 24 and 48 hours had a cytotoxic effect on WiDr cells with IC50 values of 68 µg/mL and 65 µg/mL, respectively. The combination of 1000 μg/mL 5-fluorouracil with 35 μg/mL red ginger extract at 24-hour incubation resulted in a smaller cell viability value than every single treatment. The combination treatment of 5-FU 60 μg/mL with red ginger extract at a 25 μg/mL concentration causes a more significant decrease in cell viability than a single 5-FU treatment. In conclusion, red ginger extract may increase the cytotoxic activity of 5-FU in colon adenocarcinoma WiDr cells
Sex-dependent variations in anti-nociceptive and antipyretic effects of rhizome and stem extract of Schumannianthus dichotomus Roxb. in male and female mice
Full text linkSchumannianthus dichotomus (Roxb.) is a perennial shrub from Marantaceace family. In traditional medicine, rhizome of the plant is used in fever and stem is used in earache. We aimed to substantiate these therapeutic claims by examining their effects in mice model. Antinociceptive effect was evaluated by three pain models and antipyretic effect was tested by yeast induced hyperthermia experiment. Influence of mice sexes on these pharmacological effects was examined by performing experiments separately on male and female mice. Quantitative analyses of total phenols and flavonoids were performed. Antinociceptive effects showed striking sex dimorphism. In hind paw licking test, male mice showed significant reductions in licking in both phases for both rhizome and stem extracts while significant effect was observed only in late phase in female mice. In writhing test, antinociception is more profound in male than in female. In hot plate test, stem was more effective than rhizome in male mice while female mice produced little effect for both extracts. Antipyretic experiment also showed varied effect in male and female mice; both extracts showed significant decrease in body temperatures. Rhizome showed greater effect in female mice while stem was more effective in male mice. Total phenol and flavonoid in rhizome were found 103.08 mg GAE (gallic acid equivalent) and 9.07mg QE (quercetin equivalent) respectively while in stem, these were 43.39mg GAE and 20.93 QE. Antinociceptive and antipyretic effects of rhizome and stem extracts endorsed the traditional uses of S. dichotomus. Also, differential effects based on mouse sex indicate the prerequisite of both male and female mice model in therapeutic evaluations of plant extract
Bleeding Incidence in Patients Administered with Warfarin at Secondary Hospitals in Yogyakarta Province
Full text linkWarfarin is an oral anticoagulant most-commonly prescribed for prevention and treatment of thromboembolism. It is widely acknowledged that warfarin has both narrow therapeutic index and various drug-food interactions, thus carrying the risk of subtherapeutic or bleeding. Therefore, warfarin is among the priority drugs to be evaluated to improve the quality of care for warfarin use. This study aimed to analyze the indications and dosage as well as the bleeding incidence in warfarin use at secondary hospitals in Yogyakarta. This research employed the retrospective cross-sectional design among outpatients and inpatients who received warfarin for a minimum of three days. Data of patient demographics, indications and doses of warfarin, incidence of bleeding, and other drugs interacting with warfarin were collected from the medical records for two years of research. The bleeding incidence could include conjunctival bleeding, melena, hematemesis, petechiae, purpura, ecchymosis, or hematochezia as was documented in the medical records. The research involved 139 patients with a majority of male patients and age range of >60 years. The three highest indications of warfarin use were CHF (37.41%), CHF-AF (23.74%), and AF (10.79%) with an average dose of 1.83±0.54 mg/day. Despite the administration of low doses of warfarin, four patients (2.90%) experienced bleeding with hematuria as the main clinical manifestation. This study recommends adjusting to a lower warfarin dose, particularly for the elderly who receive a combination with aspirin. In addition to a lower maintenance dose, a lower therapeutic target of INR should be further verified for Indonesian patients who receive warfarin