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"Latar Belakang: Pengobatan antimalaria dan anti-HIV secara bersamaan merupakan tantangan baru dalam penanganan koinfeksi malaria dan HIV. Primakuin merupakan substrat sekaligus inhibitor bagi CYP3A4, sedangkan ritonavir merupakan substrat, inhibitor, sekaligus inducer bagi CYP3A4. Tujuan penelitian ini adalah untuk mengukur ekspresi mRNA CYP3A4 pada kultur sel HepG2 yang diinduksi oleh pemberian primakuin dan ritonavir secara bersamaan. Metode: Pada penelitian pendahuluan, sel HepG2 diinkubasi dengan primakuin 30, 40, 50 uM; ritonavir 2, 10, 20 uM; DMSO <0,1 % sebagai kontrol negatif; atau rifampisin 20 uM sebagai kontrol positif. Adapun pada penelitian dengan perlakuan kombinasi obat, sel HepG2 diinkubasi dengan primakuin 40 uM+ritonavir 10 uM; DMSO <0,1 %; atau rifampisin 20 uM selama 72 jam. Sel dipanen menggunakan tripsin-EDTA dan RNA total diekstraksi menggunakan reagensia isolasi tripure. Setelah jumlah RNA total dikuantifikasi menggunakan alat spektrofotometer, ekspresi mRNA CYP3A4 diukur dengan real-time reverse transcription polymerase chain reaction (RT-PCR). Hasil: Terjadi peningkatan ekspresi mRNA CYP3A4 (1,22 kali lipat terhadap kontrol) pada sel HepG2 yang diinkubasi dengan primakuin dan ritonavir secara bersamaan. Hal ini menunjukkan bahwa efek induksi oleh ritonavir lebih dominan daripada efek inhibisi oleh primakuin. Kesimpulan: Pemberian primakuin dan ritonavir secara bersamaan meningkatkan ekspresi mRNA CYP3A4 in vitro.

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AbstractBackground: Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment. Methods: For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin?EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR). Results: The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine. Conclusion: Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. (Med J Indones 2012;21:3-7) Keywords: CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir"

"Tinggginya resiko polifarmasi pada pasien dislipidemia dan hipertensi menjadi alasan pentingnya untuk meningkatkan kesadaran pasien terkait resiko terjadinya interaksi obat. Tujuan dari tugas khusus ini adalah untuk memberikan edukasi dan meningkatkan kesadaran pasien terkait interaksi obat hipertensi dan dislipidemia yang dapat beresiko membahayakan dan bagaimana penanganannya dalam bentuk poster kesehatan di Apotek Kimia Farma Kranggan, Metode pelaksanaan tugas khusus  dilakukan dengan melakukan studi literatur dan pengambilan data obat-obat hipertensi dan dislipidemia yang dijual di Apotek Kimia Farma Kranggan yang kemudian hasilnya dicetak dalam bentuk poster edukasi yang menarik dan dipresentasikan ke karyawan dan dipajang di apotek agar bisa dibaca oleh pengunjung. Banyaknya pasien terutama pasien rujuk balik yang mengonsumsi kombinasi obat hipertensi dan dislipidemia di Apotek Kimia Farma Kranggan memerlukan edukasi terhadap interaksi kombinasi obat yang berbahaya dan perlu dilakukan Pemberian Informasi Obat (PIO) dan konseling rutin untuk menghindari efek samping yang tidak diinginkan.

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The high risk of polypharmacy in dyslipidemia and hypertension patients is an important reason to increase patient awareness regarding the risk of drug interactions. The purpose of this special task is to provide education and increase patient awareness regarding hypertension and dyslipidemia drug interactions that can be at risk of harm and how to handle them in the form of health posters at Apotek Kimia Farma Kranggan, The method of carrying out special tasks is carried out by conducting literature studies and collecting data on hypertension and dyslipidemia drugs sold at Apotek Kimia Farma Kranggan which then the results are printed in the form of posters Interesting education and presented to employees and displayed in pharmacies for visitors to read. The large number of patients, especially referred back patients who take a combination of hypertension and dyslipidemia drugs at Apotek Kimia Farma Kranggan, requires education on dangerous drug combination interactions and needs to be carried out Drug Information Provision (PIO) sessions and regular counseling to avoid unwanted side effects."

"Latar belakang: Penelitian ini dilakukan untuk meneliti pengaruh pemberian ritonavir dan primakuin bersamaan, yang diberikan dalam dosis tunggal atau dosis berulang pada konsentrasi plasma ritonavir pada tikus. Metode: Pada studi dengan pemberian dosis tunggal, 30 tikus Sprague Dawley jantan secara acak diberikan ritonavir 20 mg/kgBB atau ritonavir 20 mg/kgBB + primakuin 1,2 mg/kgBB atau ritonavir 20 mg/kgBB + ketokonazol 10 mg/kgBB. Ketokonazol digunakan sebagai kontrol positif penghambat metabolisme ritonavir. Pada studi dengan pemberian dosis berulang, 30 tikus Spraque Dawley secara acak diberikan ritonavir 20 mg/kgBB/hari atau ritonavir 20 mg/kgBB/hari + primaquine 1,2 mg/kgBB/hari atau ritonavir 20 mg/kgBB/hari + rifampisin 100 mg/kgBB/day. Rifampisin digunakan sebagai kontrol positif penginduksi metabolisme ritonavir. Hasil: Pada pemberian dosis tunggal, ketokonazol meningkatkan area dibawah kurva kadar plasma (AUC) ritonavir (↑114,8%, p< 0.05), sedangkan primakuin cenderung menurunkan AUC ritonavir (↓32,6%, p> 0.05). Pemberian dosis berulang menunjukkan bahwa rifampisin menurunkan AUC ritonavir (↓42,8%, p< 0.001), dan primakuin menurunkan AUC ritonavir (↓ 46,6%, p< 0.001). Kesimpulan: Pemberian primakuin dan ritonavir bersamaan dapat menurunkan AUC ritonavir. Hal ini dapat menyebabkan konsentrasi ritonavir sebagai anti-HIV tidak mencukupi, sehingga dapat menyebabkan kegagalan terapi dengan ritonavir.

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AbstractBackground: The present study was aimed to explore the effects of ritonavir and primaquine combination given as a singledose or repeated-dose compared to ritonavir alone on ritonavir plasma concentration in the rats. Methods: In single-dose study, 30 male Spraque Dawley rats were randomly allocated to receive ritonavir 20 mg/kg BW or ritonavir 20 mg/kg BW + primaquine 1.2 mg/kg BW or ritonavir 20 mg/kg BW + ketokonazole 10 mg/kg BW. Ketokonazole was used as positive control of ritonavir metabolism inhibitor. In the repeated-dose study, thirty Spraque Dawley male rats were randomly allocated to receive ritonavir 20 mg/kg BW/day or ritonavir 20 mg/kg BW/day + primaquine 1.2 mg/kg BW/day or ritonavir 20 mg/kg BW/day + rifampicin 100 mg/kg BW/day. Rifampicin was used as a positive control of ritonavir metabolism inducer. Results: In the single-dose study, ketokonazole increased the area under the plasma concentration (AUC) of ritonavir (↑114.8%, p< 0.05), while primaquine tended to decrease the AUC of ritonavir (↓ 32.6%, p> 0.05). Repeated-dose study showed that rifampicin decreases the AUC of ritonavir (↓ 42.8%, p< 0.001), and primaquine decreased the AUC of ritonavir plasma concentration (↓ 46.6%, p< 0.001). Conclusion: Concomitant administration of primaquine and ritonavir decreases the AUC of ritonavir. This effect may result in the insuffi cient concentration of ritonavir as anti-HIV, which may lead to treatment failure with ritonavir. "

"Tujuan Penyesuaian dosis dan pemilihan jenis obat penting dilakukan dalam keadaan gangguan fungsi ginjal. Penelitian observasional ini bertujuan untuk mengetahui ketepatan penyesuaian dosis dan ketepatan pemilihan obat pada pasien di ruang rawat inap Departemen Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Indonesia/Rumah Sakit Dr. Cipto Mangunkusumo, Jakarta.Metode Pasien usia 18 tahun atau lebih dengan bersihan kreatinin <60 mL/menit berdasarkan rumus Cockroft-Gault diikutkan dalam penelitian ini. Obat yang dinilai adalah obat yang ekskresinya terutama melalui ginjal dan obat-obat yang bersifat nefrotoksik. Ketepatan pemilihan dinilai berdasarkan ada/tidaknya kontraindikasi dan interaksi potensial antar obat yang digunakan, sedangkan ketepatan penyesuaian dosis didasarkan pada berbagai literature buku teks dan brosur obat. Data dikumpulkan antara bulan May sampai July 2007.Hasil Dari 43 pasien yang memenuhi kriteria inklusi, didapatkan pemakaian obat sebanyak 385 jenis, 164 jenis di antaranya mempunyai jalur ekskresi utama di ginjal dan/atau bersifat nefrotoksik. Dari 164 jenis obat tersebut, penyesuaian dosis dilakukan dengan tepat pada 142 jenis obat (86.5%), sedangkan penyesuaian yang tidak tepat terdapat pada 22 jenis obat (13.5%). Terdapat 1 pemakaian obat yang merupakan kontraindikasi, dan 15.1% dinilai potensial berinteraksi.Kesimpulan Penyesuaian dosis dan pemilihan obat pada pasien gangguan fungsi ginjal di ruang rawat inap Departemen Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Indonesia/Rumah Sakit Dr. Cipto Mangunkusumo telah dilakukan dengan baik.

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Aim Dose adjusment and drug selection is important in patient with renal dysfuction.This study was aimed to assess the accuracy of dose adjustment and drug selection for renal dysfunction patient at the Internal Medicine Ward FMUI/Dr. Cipto Mangunkusumo Hospital, Jakarta.

Methods Patients ≥ 18 years old with estimated creatinine clearance < 60 mL/minute based on Cockroft-Gault formula were included in this study. The drugs assessed were those excreted by the kidney or having nephrotoxic effect. The appropriateness of drug selection is assessed based on the preserce or not contraindication or potential of drug-drug interaction. The accuracy of dose adjustment were assessed based on information available in various textbooks, literatures, and drug brochures. Data were collected between May to July 2007.

Results Data obtained from 43 patients met the inclusion criterias demonstrated that 164 out of 385 drug prescriptions were mainly eliminated by the kidney or have nephrotoxic characteristic. Out of 164 drug prescriptions, 142 (86.5%) were appropriately adjusted, while the other 22 (13.5%) were inappropriately adjusted for the dose. There was only one contraindication for the usage of the drug and 15.1% potentially drug interaction.

Conclusion Dose adjustment and drug selections in patients with renal dysfunction at the Internal Medicine Ward FMUI/Dr. Cipto Mangunkusumo Hospital are conducted appropriately."

"The aim of this research is to reveal the relationship between the physician?s qualification and the rationality of the prescribing oral cardiovascular drugs to adult patients from drugs interactions point of view. This research is classified into descriptive analitic retrospectif survey. Data was collected from a dispensary located in East Jakarta.

The result showed that rate of the rationality of prescribing cardiovascular agents by the physician?s is 89,86%. From total prescribing, 56,45% among them was prescribed by specialist whereas the rest 43,55% was prescribed by general practitioners.

The rate of the irrational prescribing is 10,14%. From total prescribing, 78,57% among them was prescribed by general practitioners whereas the rest 21,43% was prescribed by specialist.

Based on Chi square test?s result, there is a relationship between physician?s qualification and the rationality of the prescribing oral cardiovascular drug. Specialist physicians more rational compare to general practitioners in prescribing oral cardiovascular drug."

"Penyebab kematian tingkat pertama dapat disebabkan oleh Stroke, diikuti dengan Penyakit Jantung Iskemik, Diabetes, Tuberkulosa, Sirosis, diare, PPOK, Alzheimer, Infeksi saluran napas bawah dan Gangguan neonatal serta kecelakaan lalu lintas. Penyakit-penyakit tersebut, merupakan penyakit yang sering terjadi pada rentang usia dewasa dari 30 tahun keatas, terlebih pada populasi geriatri/lansia atau lebih dari >55 tahun dan memiliki pola pengobatan yang membutuhkan berbagai jenis terappi baik berindikasi sesuai diagnosis atau hanya terapi simtomatis. Pada polifarmasi, beberapa kejadian terkait reaksi obat adalah interaksi antar obat, tidak jelasnya tujuan pengobatan, peningkatan waktu terapi, reaksi obat tidak diinginkan dari yang ringan seperti iritasi atau alergi hingga adanya morbiditas/kematian. Laporan Praktek Kerja Apoteker ini bertujuan untuk mengkaji resep polifarmasi yang masuk ke dalam apotek Roxy Pitara.

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The first cause of death can be stroke, followed by ischemic heart disease, diabetes, tuberculosis, cirrhosis, diarrhea, COPD, Alzheimer's, lower respiratory tract infections and neonatal disorders and traffic accidents. These diseases are diseases that often occur in the adult age range from 30 years and above, especially in the geriatric/elderly population or over 55 years and have treatment patterns that require various types of therapy, whether indicated according to the diagnosis or only symptomatic therapy. In polypharmacy, several incidents related to drug reactions are interactions between drugs, unclear goals of treatment, increased therapy time, unwanted drug reactions ranging from mild ones such as irritation or allergies to morbidity/death. This Pharmacist Work Practices Report aims to examine polypharmacy prescriptions entered into the Roxy Pitara pharmacy."

"Drug-drug interactions in pharmaceutical development comprehensively reviews the relevant science, industrial practice, and regulatory agency positions on drug-drug interactions. It focuses on the evaluation of potential drug-drug interactions, allowing researchers to address risk factors before a drug is put to market. The book covers both clinical and nonclinical aspects for understanding drug-drug interactions as well as in vitro and in vivo studies for use in studying interactions at the drug discovery stage."