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Abstrak :
Latar Belakang : Keberhasilan pengobatan antihipertensi dipengaruhi banyak hal, salah satunya adalah faktor genetik, termasuk perbedaan ras dan aktivitas renin plasma (ARP). Perbedaan ras, berkaitan dengan ARP, mungkin dapat memberikan perbedaan respon terhadap obat antihipertensi. Aktivitas renan plasma dan perbandingan efektifitas obat antihipertensi (lisinopril dan amlodipin) pada ras melanesia di Provinsi Papua belum pernah diteliti. Tujuan : Mengukur aktivitas renin plasma dan membandingkan efektifitas obat lisinopril dan amlodipin pada pasien hipertensi ras melanesia untuk menurunkan tekanan darah. Metode : Pada awal penelitian, 68 subjek berhasil direkrut, dilakukan randomisasi dan dibagi ke dalam dua kelompok. Sebanyak 34 subjek mendapat lisinopril 5 mg dan 34 subjek mendapat amlodipine 2.5 mg. Tekanan darah, ARP dan karakteristik dasar lainnya diukur sebelum intervensi, dan kemudian di follow up tiap minggu. Subjek yang belum mencapai target tekanan darah akan diberikan peningkatan dosis obat, lisinopril 10 hingga 20 mg dan amlodipin 5 hingga 10 mg. Pada akhir penelitian (minggu keempat), tekanan darah diukur sebagai luaran klinis. Sebanyak 7 subjek drop out, 4 subjek pada kelompok lisinopril dan 3 subjek pada kelompok amlodipin. Hasil : Aktivitas renin plasma pada populasi penelitian ini 1.6 ng/ml/jam (normal). Karakteristik dasar klinis tidak berbeda antara kedua kelompok, termasuk rerata tekanan darah sebelum intervensi dan ARP. Pada kedua kelompok didapatkan penurunan tekanan darah yang signifikan setelah intervensi, baik pada tekanan darah sistolik (TDS), distolik (TDD) dan tekanan nadi (TN). Namun, pada penelitian ini, perbedaan respon penurunan tekanan darah antara kelompok lisinopril dan amlodipin tidak berbeda (TDS 24.6 ± 9.3 vs 25.9 ± 8.9 mmHg, p=0.56; TDD 13.3 ± 5.5 vs 11.4 ± 4.8 mmHg, p=0.15; TN 17.1 ± 5.6 vs 16.3 ± 5.0 mmHg, p=0.55). Kesimpulan : Aktivitas renin plasma pada pasien hipertensi ras melanesia normal dan pemberian lisinopril tidak menunjukkan perbedaan penurunan respon penurunan tekanan darah dibandingkan dengan amlodipin. ......Background: The success of antihypertensive treatment are influenced by many factors, one of which are genetic factors, including differences in race and plasma renin activity (PRA). Racial differences, regarding PRA, may give different response to antihypertensive drugs. Plasma renin activity and comparison of the effectiveness of antihypertensive medications (lisinopril and amlodipine) in the Melanesian race in the province of Papua have not been investigated. Objectives: To measure plasma renin activity and compare the effectiveness of lisinopril and amlodipine in melanesian hypertensive patients to reduce blood pressure. Methods: Sixty eight subjects were randomly assigned into 2 groups, those receiving lisinopril 5 mg (34 subjects) and amlodipine 2.5 mg (34 subjects). Blood pressure, PRA and other baseline characteristics were measured before the intervention, and then evaluated every week. Dose of lisinopril and amlodipine will be increased in subjects who have not achieved blood pressure target, 10 mg to 20 mg and 5 mg to 10 mg, respectively. At the end of the fourth week, blood pressure is measured as the main clinical outcome. Seven subjects were drop out, four from lisinopril group and three from amlodipin group. Results: Plasma renin activity in this study population was 1.6 ng/ml/h (normal). Baseline characteristics did not differ between two groups, including blood pressure and PRA before intervention. Significant decrease in blood pressure occurred in both group after the intervention, including systolic blood pressure (SBP) , diastolic (DBP) and mean arterial pressure (MAP). However, there are no differences in blood pressure reduction between lisinopril and amlodipine groups. (SBP 24.6 ± 9.3 vs 25.9 ± 8.9 mmHg, p=0.56; DBP 13.3 ± 5.5 vs 11.4 ± 4.8 mmHg, p=0.15; MAP 17.1 ± 5.6 vs 16.3 ± 5.0 mmHg, p=0.55). Conclusion: Plasma renin activity in melanesian hypertensive patients was normal and administration of lisinopril showed no difference in blood pressure reduction compared with amlodipine.

Abstrak :
ABSTRAK
Beberapa penelitian dilakukan untuk mengevaluasi penggunaan analgesik dalam menginduksi kerusakan hati pada hewan model. Penggunaan hewan model digunakan dalam studi preklinik untuk mengevaluasi aktivitas obat. Penelitian ini dilakukan untuk membandingkan kondisi kerusakan hati yang diinduksi parasetamol dan natrium diklofenak dan mengevaluasi efek hepatoprotektif lisinopril sebagai obat off label pada hewan model hepatotoksik. Orientasi pembentukan hewan model dilakukan beberapa kali pada beberapa variasi dosis parasetamol melalui rute oral dan natrium diklofenak melalui rute intraperitoneal. Selanjutnya, hewan uji digunakan untuk mengevaluasi pemberian lisinopril. Tiga puluh ekor tikus, dibagi menjadi 5 kelompok perlakuan (normal, kontrol negatif, dan lisinopril 10, 20, dan 40 mg/kg BB) diberikan perlakuan selama 14 hari melalui rute administrasi oral. Dua puluh empat jam setelah administrasi, parasetamol (2000 mg/kg BB) diberikan secara oral dan 6 jam setelah administrasi, sampel plasma dikumpulkan untuk dianalisis kadar AST, ALT, dan ALP sebagai biomarker parameter kerusakan hepatosit dan SOD dan GPx sebagai gambaran kadar antioksidan plasma. Gambaran morfologi hati juga diamati. Hasilnya menunjukkan bahwa parasetamol menimbulkan kerusakan lebih parah dan lebih dapat diimplementasikan dalam studi hepatoprotektif dibandingkan natrium diklofenak. Dosis parasetamol yang memberikan perbedaan signifikan (p<0,05) terhadap kelompok normal adalah 2000 mg/kg BB dan diukur pada waktu 6 jam setelah administrasi. Uji evaluasi lisinopril menunjukkan bahwa terdapat perbedaan yang signifikan (p<0,05) antara kelompok perlakuan dengan kelompok kontrol negatif pada parameter AST, ALT, dan ALP. SOD dan GPx menunjukkan nilai yang lebih tinggi dibanding kontrol negatif, namun tidak terdapat perbedaan yang signifikan pada masing-masing dosis. Berdasarkan hasil tersebut, dapat disimpulkan bahwa parasetamol (2000 mg/kg BB, 6 jam) lebih baik digunakan pada hewan model hepatotoksik dibandingkan natrium diklofenak dan pemberian model lisinopril (40 mg/kg BB) selama 14 hari memiliki potensi sebagai hepatoprotektor pada hewan model hepatotoksik.

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ABSTRACT
Several studies have been performed to investigate the analgesic drugs for inducing the liver injury in animal model. It is used as animal model to perform the preclinic study in evaluating the activity of drugs. This study was conducted to compare the conditions of paracetamol and sodium diclofenac-induced liver injury and to experimentally evaluate the protective effect of lisinopril as off label drug in hepatotoxic animal models. The orientation for the formation of animals hepatotoxic model was repeated at various doses of paracetamol orally and sodium diclofenac via intraperitoneal for various timeframes. Furthermore, the animal model was used to evaluate the lisinopril administration. A total of 30 rats in 5 treatment groups (normal, negative control, and lisinopril at dose of 10, 20, and 40 mg/kg/BW/day) were used and treated for 14 days via oral administration route. Twenty four hours after administration, paracetamol (2000 mg/kg BW) were given orally and 6 hours after the plasma samples were collected to analyze AST, ALT, and ALP as paramater biomarkers for hepatocyte damage and SOD and GPx as illustrations of plasma antioxidant activity. Morphological observations were also carried out. The result showed that paracetamol cause more damage and that could be implemented in the hepatoprotective study than sodium diclofenac induction. The dose of paracetamol which gives a significant different (p<0,05) to the normal group is 2000 mg/kg BW and measured at 6 hours after administration. The evaluation of lisinopril showed that there were significant difference (p<0,05) between the treatment groups compared to negative control group on AST, ALT, and ALP parameters. In addition, SOD and GPx activity showed a higher value compared to the negative control group but there were no significant differences in each dose. Based on the the result, it be concluded that paracetamol (2000 mg/kg BW, 6 hours) could be better used as hepatotoxic animal model compared to sodium diclofenac and lisinopril administration (40 mg/kg BW) for 14 days has the potential as a hepatoprotector in animal model.