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Acil Aryadi

Perbandingan efektifitas antara lisinopril dan amlodipin terhadap penurunan tekanan darah pada pasien hipertensi ras melanesia = Effectiveness comparison between lisinopril and amlodipine in melanesian patients with hypertension

"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."

Jakarta: Fakultas Kedokteran Universitas Indonesia, 2015

SP-Pdf

UI - Tugas Akhir Universitas Indonesia Library

Asma Fitriani

Evaluasi model hepatotoksisitas akut secara eksperimental dan efek hepatoprotektif lisinopril terhadap fungsi hati tikus putih hepatotoksik = Evaluation of experimental acute hepatotoxicity in animal model and hepatoprotective effect of lisinopril on liver function in hepatotoxic albino rats / Asma Fitriani

"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.

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."

2019

S-Pdf

UI - Skripsi Membership Universitas Indonesia Library

Ayuthia Putri Sedyawan

Perbandingan efek lisinopril dan amlodipin terhadap kekakuan pembuluh arteri pada pasien hipertensi yang belum pernah diobati = aortic stiffness in native hypertension amlodipin versus lisinopril administration ashalina study

"[ABSTRAK

Latar belakang. Hipertensi adalah faktor risiko kardiovaskular yang penting. Kekakuan arteri meningkat seiring dengan peningkatan usia, hipertensi, diabetes mellitus, aterosklerosis, dan lainnya. Kekakuan arteri dapat diukur secara non-invasif dengan menggunakan alat carotid-femoral pulse wave velocity (CF-PWV), dimana alat ini mengukur kecepatan gelombang nadi yang berjalan dari arteri karotis komunis ke arteri femoralis. Obat antihipertensi telah diketahui memiliki kemampuan terhadap kekakuan arteri, namun berbeda efektifitasnya.

Tujuan. Melihat perbandingan efek pemberian penghambat enzim pengubah angiotensin dan penyekat kanal kalsium terhadap kekakuan arteri pada pasien hipertensi yang belum pernah diobati sebelumnya.

Metode. Uji klinis acak dengan tersamar ganda, dilakukan di RS Pusat Jantung dan Pembuluh Darah Harapan Kita (Maret-Mei 2015) terhadap 54 subyek usia 30-50 tahun. Subyek dibagi menjadi dua grup, grup lisinopril (n=27) dan amlodipin (n=27). Tekanan darah dan CF-PWV diukur sebelum dan setelah intervensi.

Hasil. Terdapat penurunan tekanan darah dan sesudah terapi untuk kedua grup. Delta penurunan CF-PWV untuk kedua intervensi menujukkan hasil yang signifikan (P value <0.001). Lisinopril memiliki penurunan delta CF-PWV yang lebih signifikan dibandingkan amlodipin. (P value <0.001 IK 95% 0.2 - 0.5).

Kesimpulan. Penelitian ini membuktikan adanya perbedaan bermakna terhadap CF-PWV pada grup yang diberikan lisinopril dan amlodipin, dimana lisinopril memiliki delta penurunan PWV yang lebih signifikan.

ABSTRACT

Background. Hypertension is a well-recognized cardiovascular risk factors. Arterial stiffness increases with age, hypertension, diabetes mellitus, atherosclerosis, etc. Arterial stiffness can be assessed noninvasively by carotid-femoral pulse wave velocity (CF-PWV) measurement, that is, the velocity of the pulse wave to travel a given distance between carotid and femoral artery. Antihypertensive drugs have been implicated in arterial stiffness diminishment but vary in effectiveness.

Objective. To examine the difference in arterial stiffness reduction in young native hypertensive subjects that was given ace-inhibitor or calcium channel blocker.

Methods. A double blind randomized clinical trial was conducted in National Cardiovascular Centre Harapan Kita to 54 subjects (30-50 years old), from March to May 2015. Subjects were divided into lisinopril 5mg (n=27) and amlodipine 5mg (n=27) groups. Blood pressure and CF-PWV were measured before and 4 weeks post therapy.

Results. Blood pressure reduction was found before and after treatment for both groups. CF-PWV for lisinopril and amlodipine showed significant reduction (p-value <0.001). Lisinopril had more significant decrease in CF-PWV (P value <0.001 CI 95% 0.2 - 0.5).

Conclusion. There was a statistically significant difference in CF-PWV reduction between lisinopril and amlodipin administration to patients with native hypertension, with lisinopril having the larger effect., Background. Hypertension is a well-recognized cardiovascular risk factors.

Arterial stiffness increases with age

subjects with diabetes mellitus,

and hypertension

and is also enhanced in

atherosclerosis,

and end-stage renal disease.

Arterial stiffness can be assessed noninvasively with the use of carotid-femoral

pulse wave velocity (CF-PWV) measurement, that is, the velocity of the pulse

wave to travel a given distance between carotid and femoral artery.

Antihypertensive drugs have been implicated in arterial stiffness diminishment

but vary in their degree of effect. The calcium channel blocker having its

“destiffening” effect have been widely known to reduce arterial stiffness.

However, the renin-angiotensin system inhibitors proved to be superior to all

other antihypertensive drugs in reducing arterial stiffness.

Objective. The aim of this study was to examine the difference in arterial stiffness

reduction in native hypertensive subjects that was given ace-inhibitor or calcium

channel blocker for four weeks, by measuring the CF-PWV.

Methods. A double blind randomized clinical trial was conducted in National

Cardiovascular Centre Harapan Kita (NCCHK) to 54 subjects with native

hypertension between the age of 30-50 years old, from March to May 2015.

Subjects were divided into two groups: lisinopril 5mg (n=27) and amlodipine 5mg

(n=27). Blood pressure and CF-PWV were measured before and after 4 weeks of

therapy. Statistical analysis was done using bivariat and multivariat analisis to

determine the significance of arterial stiffness reduction.

Results. There was a reduction in blood pressure (systole, diastole, mean arterial

pressure) before and after the treatment for both groups. However although it was

clinicaly significant, statistically it was not (P value >0.05). Nonetheless, CFPWV

for

lisinopril

and

amlodipin

showed

significant

reduction

with

both

p-value

were

<0.001 (2.09±0.280, CI 95% 1.80-2.2 and 1.77±0.340, CI 95% 1.6-1.9).

When both drugs were compared using multivariate analysis, lisinopril was

proved to have a more significant decrease in CF-PWV (P value <0.001 CI 95%

0.2 - 0.5).

Conclusion. This study proved that there was a statistically significant difference

in CF-PWV reduction between lisinopril and amlodipin administration to patients with native hypertension, with lisinopril having the larger effect. ]"

Fakultas Kedokteran Universitas Indonesia, 2015

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UI - Tugas Akhir Universitas Indonesia Library

Yusak Alfrets Porotuo

Respon tekanan darah pasien hipertensi ras Melanesia dan ras non Melanesia dengan pemberian penyekat enzim angiotensin = Blood pressure response in hypertensive patients Melanesian race and non Melanesian race with angiotensin converting enzyme inhibitors

"ABSTRAK

Latar belakang. Hipertensi merupakan salah satu kondisi yang paling banyak

ditemukan pada pelayanan kesehatan primer yang dapat meningkatkan mortalitas dan

morbidita apabila tidak mendapatkan pengobatan yang tepat. Beberapa penelitian

menunjukkan respon penurunan tekanandarah pada ras kulit hitam berbeda dibanding

ras kulit putih dengan antihipertensi golongan penyekat EKA, hal ini ditunjang

dengan perbedaan PRA pada kedua kelompok ras ini. Belum terdapat data tentang

respon tekanan darah pasien hipertensi ras melanesiadengan pemberian penyekat

EKA yang ditunjang dengan pemeriksaan kadar PRA pada kelompok ras ini.

Objektif. Menilai apakah terdapat perbedaan respon terapi terhadap penyekat enzim

konversi angiotensin (EKA) pada pasien hipertensi ras melanesia dan ras non

melanesia.

Metode. Penelitian ini adalah penelitian kohort prospektif yangdilakukan di kota

Jayapura bulan September-November 2015terhadap 85 subyek usia 30 sampai 55

tahun dengan hipertensi yang belum pernah diobati sebelumnya. Subyek terbagi atas

2 grup yaitu ras Melanesia (n=34) dan ras Non Melanesia(n=51). Kedua grup tersebut

diberikan lisinopril dosis awal 5 mg. Pemeriksaan tekanan darah dilakukan pada awal

dan diulangi setiap 7 hari selama 4 minggu berturut-turut.

Hasil. Terdapat perbedaan respon tekanan darah pasien hipertensi ras Melanesia dan

ras Non Melanesia. Perbedaan tekanan darah sistolik sebesar 24,5 ± 9,4 mmHg pada

subyek ras Melanesia dan pada subyek Non Melanesia sebesar 34,5 ± 13,5 mmHg

(p<0,001). Perbedaan tekanan darah diastolik subyek ras Melanesia sebesar 13,3±5,5

mmHg dan pada subyek Non Melanesia sebesar 22,6±9,3 mmHg (p<0,001).

Perbedaan tekanan rerata arteri pada subyek ras Melanesia sebesar 17,1±5,6 mmHg

dan pada subek ras Non Melanesia sebesar 26,21±8,8 mmHg (p<0,001). Reratakadar

Plasma Renin Activity (PRA) pada subyek ras Melanesia sebesar 1,48[1,86]

ng/ml/jam dan pada subyek ras Non Melanesia rerata kadar PRA sebesar 1,1[1,47]

ng/ml/jam. Tidak terdapat hubungan yang bermakna rerata kadar PRA pada kedua

kelompok ras ini (p=0,564).

Kesimpulan. Terdapat perbedaan penurunan tekanan darah (sistolik, diastolik dan

tekanan rerata arteri) dengan pemberian penyekat EKA pada kelompok ras Melanesia

dan kelompok ras Non Melanesia dan hal ini tidak berhubungan bermakna dengan

rerata kadar PRA pada kedua kelompok ini sehingga kemungkinan terdapat faktor lain yang mempengaruhi respon penurunan tekanan darah dengan penyekat EKA.ABSTRACT

Hypertension is one of the most commonconditionsin primary health

care that increase mortality and morbidity if it does not receive appropriate therapy.

Several studies show that blacks response differently compared with white in

conjunction with a decrease of blood pressure in response to administer ACE

inhibitor. The studies supported by PRA differences in both group of race. There are

no data ofblood pressure response in hypertensive patientsinMelanesian race by

administeringACE inhibitor supported withPRA levels examination in thisgroup of

race.

Objective. To compare therapeutic response ofangiotensin converting enzyme

blockers (ACE)inhibitorinreducing blood pressure between MelanesianandNon

Melanesian hipertensive patients.

Method. This study is a prospective cohort study conducted in the city of

Jayapura September to November 2015. We found85 subjects aged 30 to 55 years

oldwith hypertensionnever be treated before. Subjects are divided into two

groups, namely the Melanesian race (n = 34) and non Melanesian race (n = 51).

Both groups were given an initial dose of 5 mg of lisinopril. Blood pressure

checks performed at baseline and repeated every 7 days for 4 weeks in a row.

Results. There are differences in the response of blood pressure in hypertensive

patientofMelanesian race and Non Melanesiarace. Reduction ofsystolic blood

pressure of 24.5 ± 9.4 mmHg in subject Melanesian race and on the subject of

Non Melanesian 34.5 ± 13.5 mmHg (p < 0.001). Reduction ofdiastolic blood

pressure of subjectsMelanesians of 13.3 ± 5.5 mmHg, and on the subject of Non

Melanesia 22.6 ± 9.3 mmHg (p<0.001). Reduction ofmean arterial pressure in

subjectMelanesian race at 17.1 ± 5.6 mmHg andNon Melanesian race at 26.21 ±

8.8 mmHg (p < 0.001). Mean Plasma Renin Activity (PRA) on the subject of the

Melanesian race at 1.48 [1.86] ng/ml/h and on the subject of nonMelanesian race

PRA average level of 1.1 [1.47] ng/ml/hr. There was no significant relationship

mean PRA levels in both these racial groups (p = 0.564).

Conclusion. There aredifferences in blood pressure reduction (systolic, diastolic

pressure and mean arterial pressure) with administer of ACE inhibitor in

Melanesianand Non Melanesiagroup of race. There is no significant relation with

averagePRAlevels in both group of race. Another factors affectsresponses of reduction blood pressure with administer ofACEinhibitor may be considered.;Background. Hypertension is one of the most commonconditionsin primary health