SKRIPSI

Retno Aprillia Handayani STUDI PENGGUNAAN GOLONGAN CALCIUM

CHANNEL BLOCKER (CCB) PADA PASIEN

CHRONIC KIDNEY DISEASE (CKD) (Penelitian Dilakukan di Instalasi Rawat Inap RS

Muhammadiyah Lamongan)

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS MUHAMMADIYAH MALANG

2016

iii

KATA PENGANTAR

Bismillahirrohmanirrohim

Assalamu’alaikum warohmatullahi wabarokatuh

Puji syukur tercurahkan kepada ALLAH SWT, Tuhan semesta alam

karena berkat rahmat dan ridhoNya, penulis dapat menyelesaikan skripsi yang

berjudul STUDI PENGGUNAAN GOLONGAN CALCIUM CHANNEL

BLOCKER (CCB) PADA PASIEN CHRONIC KIDNEY DISEASE (CKD)

(Penelitian Dilakukan di Instalasi Rawat Inap RS Muhammadiyah

Lamongan)

Skripsi ini diajukan untuk memenuhi syarat untuk mencapai gelar Sarjana

Farmasi pada Program Studi Farmasi Fakultas Ilmu Kesehatan Universitas

Muhammadiyah Malang. Dalam penyusunan skripsi ini penulis tidak terlepas dari

peranan pembimbing dan bantuan dari seluruh pihak. Oleh karena itu, dengan

segala kerendahan hati, penulis ingin mengucapkan banyak terima kasih kepada:

1. ALLAH SWT, tuhan semesta alam yang memberkan rahmat, nikmat dan

Karunia-Nya, Nabi Muhammad SAW yang sudah menuntun kita menuju

jalan yang benar.

2. Bapak Yoyok Bekti P., M.Kep., Sp.Kom.,,selaku Dekan Fakultas Ilmu

Kesehatan Universitas Muhammadiyah Malang yang telah memberikan

kesempatan penulis menuntut ilmu di Fakultas Ilmu Kesehatan Universitas

Muhammadiyah Malang.

3. Ibu Nailis Syifa’, S.Farm., M.Sc., Apt., selaku Ketua Program Studi

Farmasi Universitas Muhammadiyah Malang yang telah memberi motivasi

dan kesempatan penulis menuntut ilmu di Program Studi Farmasi

Universitas Muhammadiyah Malang.

4. Bapak Drs. Didik Hasmono, M.S., Apt., Ibu Nailis Syifa’, S.Farm., M.Sc.,

Apt. dan Ibu Rully Yuliandhari, S.Farm, M.Farm.Klin., Apt., Selaku

Dosen Pembimbing I, II dan III, disela kesibukan Bapak dan Ibu masih

bisa meluangkan waktu untuk membimbing dan memberi pengarahan dan

dorongan moral sampai terselesaikannya skripsi ini.

iv

5. Ibu Hidajah Rachmawati, S.Si., Apt., Sp.FRS dan Ibu Lilik Yusetyani

Apt., Sp.FRS., selaku Dosen Penguji I dan II, yang telah banyak

memberikan saran dan masukan demi kesempurnaan skripsi ini.

6. Ibu Siti Rofida, S.Si., Apt., M.Farm., selaku Dosen wali saya yang telah

banyak membantu dan membimbing saya selama masa perkuliahan.

7. Orang Tuaku tercinta, Johansyah, S.E., dan Astuty Ambulyani, Amd.Kep.,

yang tiada hentinya memotivasi dan sabar mendoakan untuk kebaikan dan

kesuksesan anak-anaknya.

8. Sahabat seperjuangan skripsi klinis maupun bidang lainnya Hafiz, Ovi,

Ivone, Viar, Pipit, Ana, Gitta, Uti, Delle, Aeny, Elok dan yang lainnya,

terima kasih atas kebersamaan, bantuan, dan semangat kerjasamanya

sehingga skripsi ini dapat terwujud.

9. Teman-teman kost Veteran Dalam dek Yenny, dek Ria, Dek Kiki, Ayuni,

dek Laras, Lika dan yang lainnya terima kasih untuk selalu memangati

saya.

10. Teman-teman budak Bulungan yang selalu menanyakan saya kapan lulus,

terima kasih banyak atas motivasinya.

11. Untuk semua pihak yang belum disebutkan namanya, penulis mohon maaf

dan terimakasih yang sebesar-besarnya.

Penulis menyadari bahwa skripsi ini jauh dari kesempurnaan, oleh karena

itu penulis mengharapkan saran dan kritik yang membangun dari pembaca demi

kebaikan skripsi ini. Semoga penulisan ini dapat berguna bagi penelitian

berikutnya, amin.

Wassalamu’alaikum warohmatullohi wabarokatuh

Malang,

Penyusun

(Retno Aprillia Handayani)

ix

DAFTAR ISI

LEMBAR PENGESAHAN ............................................................................................. i

KATA PENGANTAR ........................................................................................... iii

RINGKASAN ......................................................................................................... v

ABSTRAK ............................................................................................................ vii

ABSTRACT ......................................................................................................... viii

DAFTAR ISI .................................................................................................................... ix

DAFTAR TABEL ......................................................................................................... xiii

DAFTAR GAMBAR .................................................................................................... xiv

DAFTAR LAMPIRAN ......................................................................................... xv

DAFTAR SINGKATAN ..................................................................................... xvi

BAB 1 PENDAHULUAN .............................................................................................. 1

1.1 Latar Belakang ............................................................................................... 1

1.2 Rumusan Masalah .......................................................................................... 4

1.3 Tujuan Penelitian ........................................................................................... 4

1.3.1 Tujuan Umum .............................................................................................. 4

1.3.2 Tujuan Khusus ............................................................................................. 4

1.4 Manfaat Penelitian ......................................................................................... 5

BAB II TINJAUAN PUSTAKA .................................................................................... 6

2.1 Hipertensi ....................................................................................................... 6

2.1.1 Definisi Hipertensi ............................................................................... 6

2.1.2 Epidemologi Hipertensi ....................................................................... 6

2.1.3 Manifestasi Klinis Hipertensi .............................................................. 7

2.1.4 Klasifikasi Hipertensi .......................................................................... 8

2.1.5 Etiologi Hipertensi ............................................................................... 9

2.1.5.1 Hipertensi Primer/Esensial ........................................................ 9

x

2.1.5.2 Hipertensi Sekunder ................................................................ 10

2.1.6 Faktor Resiko Hipertensi ................................................................... 10

2.1.6.1 Faktor yang Tidak Dapat Dikontrol ........................................ 10

2.1.6.2 Faktor yang Dapat Dikontrol ................................................... 11

2.1.7 Patofisiologi Hipertensi ..................................................................... 13

2.1.8 Komplikasi Hipertensi ........................................................................ 15

2.2 Chronic Kidney Disease ................................................................................. 16

2.2.1 Tinjauan Tentang Ginjal .................................................................... 16

2.2.2 Anatomi dan Fisiologi Ginjal ............................................................ 17

2.2.3 Definisi Chronic Kidney Disease ...................................................... 19

2.2.4 Epidemologi Chronic Kidney Disease............................................... 19

2.2.5 Manifestasi Chronic Kidney Disease................................................. 21

2.2.6 Klasifikasi Chronic Kidney Disease .................................................. 22

2.2.7 Etiologi Chronic Kidney Disease ...................................................... 22

2.2.8 Faktor Resiko Chronic Kidney Disease ............................................. 23

2.2.9 Patofisiologi Chronic Kidney Disease ............................................... 23

2.2.10 Tanda dan Gejala Chronic Kidney Disease ..................................... 27

2.2.11 Komplikasi Chronic Kidney Disease............................................... 28

2.2.12 Penatalaksanaan Chronic Kidney Disease ....................................... 29

2.3 Tinjauan Terapi Antihipertensi pada Pasien Chronic Kidney Disease ........... 35

2.3.1 Angiotensin Converting Enzyme Inhibitor (ACE-I) ......................... 35

2.3.2 Angiotensin Receptor Blocker (ARB) ............................................... 37

2.2.3 Diuretik .............................................................................................. 37

2.3.6 Calcium Channel Blocker (CCB) ...................................................... 38

2.3.6.1 Non-Dihidropiridin .................................................................. 40

2.3.6.1.1 Diltiazem ..................................................................... 41

xi

2.3.6.1.2 Verapamil .................................................................... 42

2.3.6.2 Dihidropiridin .......................................................................... 45

2.3.6.2.1 Amlodipin ................................................................... 46

2.3.6.2.2 Nifedipin ..................................................................... 49

2.3.6.2.3 Nicardipin .................................................................... 51

BAB III KERANGKA KONSEPTUAL ..................................................................... 53

3.1 Kerangka Konseptual ..................................................................................... 53

3.2 Kerangka Operasional .................................................................................... 56

BAB IV METODE PENELITIAN .............................................................................. 57

4.1 Rancangan Penelitian ................................................................................... 57

4.2 Bahan Penelitian .......................................................................................... 57

4.2.1 Kriteria Inklu dan Ekslusi .................................................................... 57

4.3Populasi dan Sampel ...................................................................................... 58

4.3.1 Populasi ................................................................................................ 58

4.3.2 Sampel .................................................................................................. 58

4.4 Instrumen Penelitian .................................................................................... 58

4.5 Lokasi dan Waktu Penelitian ....................................................................... 58

4.6 Definisi Operasional Parameter Penelitian .................................................. 58

4.7 Metode Pengumpulan Data .......................................................................... 59

4.8 Analisa Data ................................................................................................. 60

BAB V HASIL PENELITIAN ............................................................................. 62

5.1 Data Demografi ............................................................................................ 62

5.1.1 Jenis Kelamin ........................................................................................ 63

5.1.2 Usia ....................................................................................................... 63

5.1.3 Status Pasien ......................................................................................... 63

5.2 Faktor Resiko ................................................................................................ 64

xii

5.3 Diagnosa Penyerta ........................................................................................ 64

5.4 Klasifikasi Chronic Kidney Disease ............................................................. 65

5.5 Profil Tekanan Darah .................................................................................... 65

5.6 Terapi Antihipertensi yang diterima pasien Chronic Kidney Disease .......... 66

5.6.1 Distribusi Antihipertensi Tunggal ......................................................... 66

5.6.2 Distribusi Kombinasi 2 Antihipertensi ................................................. 67

5.6.3 Distribusi Kombinasi 3 Antihipertensi ................................................. 68

5.6.4 Distribusi Kombinasi 4 Antihipertensi ................................................. 70

5.6.5 Distribusi Kombinasi 5 Antihipertensi ................................................. 71

5.7 Distribusi terapi penyerta yang diterima pasien Chronic Kidney Disease ... 71

5.8 Perubahan Dosis, Rute, Frekuensi, dan Sediaan ........................................... 72

5.9 Lama Terapi .................................................................................................. 73

5.10 Kondisi Saat Dipulangkan .......................................................................... 73

5.11 Pasien Meninggal ........................................................................................ 73

BAB VI PEMBAHASAN ..................................................................................... 75

BAB VII KESIMPULAN DAN SARAN ............................................................. 88

7.1 Kesimpulan ................................................................................................... 88

7.2 Saran ............................................................................................................. 88

DAFTAR PUSTAKA .................................................................................................... 89

xiii

DAFTAR TABEL

Tabel Halaman

2.1 Klasifikasi Hipertensi .................................................................................... 8

2.2 Klasifikasi Chronic Kidney Disease ........................................................... 21

2.3 Karakteristik berbagai Calcium Channel Blocker....................................... 39

5.1 Distribusi jenis kelamin pasien Chronic Kidney Disease ........................... 63

5.2 Distribusi usia pasien Chronic Kidney Disease .......................................... 63

5.3 Distribusi jenis kelamin pasien Chronic Kidney Disease ........................... 63

5.4 Distribusi faktor resiko pasien Chronic Kidney Disease ............................ 64

5.5 Distribusi diagnosa penyerta pasien Chronic Kidney Disease .................... 64

5.6 Distribusi klasifikasi pasien Chronic Kidney Disease ................................ 65

5.7 Distribusi profil tekanan darah pasien Chronic Kidney Disease ................ 65

5.9 Distribusi antihipertensi yang diterima pasien Chronic Kidney Disease .... 66

5.10 Distribusi antihipertensi tunggal ................................................................. 66

5.11 Distribusi kombinasi 2 antihipertensi ......................................................... 67

5.12 Distribusi kombinasi 3 antihipertensi ......................................................... 68

5.13 Distribusi kombinasi 4 antihipertensi ......................................................... 70

5.14 Distribusi kombinasi 5 antihipertensi ......................................................... 71

5.15 Distribusi terapi penyerta yang diterima pasien Chronic Kidney Disease .. 71

5.16 Distribusi perubahan dosis, rute, frekuensi, dan sediaan ............................ 72

5.16 Distribusi kondisi saat dipulangkan pasien Chronic Kidney Disease ......... 73

5.16 Distribusi lama terapi pasien Chronic Kidney Disease ............................... 73

5.17 Pasien meninggal ........................................................................................ 73

xiv

DAFTAR GAMBAR

Gambar Halaman

2.1 Etiologi penyebab Hipertensi ........................................................................ 9

2.2 Patofisiologi Hipertensi ............................................................................... 13

2.3 Gambaran umum struktur ginjal ................................................................. 16

2.4 Prevalensi Chronic Kidney Disease ............................................................ 19

2.5 Patofisiologi Chronic Kidney Disease ........................................................ 25

2.6 Struktur Kimia Diltiazem ............................................................................ 40

2.7 Struktur Kimia Verapamil ........................................................................... 42

2.8 Struktur Kimia Amlodipin .......................................................................... 45

2.9 Struktur Kimia Nifedipin ............................................................................ 48

2.10 Struktur Kimia Nikardipin .......................................................................... 50

3.1 Kerangka Konseptual .................................................................................. 55

3.2 Kerangka Operasional .................................................................................. 56

5.1 Skema Inklusi dan Ekslusi ........................................................................... 62

xv

DAFTAR LAMPIRAN

Lampiran .................................................................................................... Halaman

Lampiran 1 : Riwayat Hidup ................................................................................ 103

Lampiran 2 : Surat Pernyataan ............................................................................. 104

Lampiran 3 : Surat Etikal Klirens ........................................................................... 105

Lampiran 4 : Tabel Induk ..................................................................................... 106

Lampiran 5 : Lembar Pengumpulan data ............................................................. 134

xvi

DAFTAR SINGKATAN

ADH : Anti Diuretik Hormone

ACE-I : Angiotensin Converting Enzyme Inhibitor

ACR : Albumin Creatinine Ratio

AKI : Acute Kidney Injury

ARB : Angiotensin Receptor Blocker

BPJS : Badan Penyelenggara Jaminan Nasional

Ca : Kalsium

CCB : Calcium Channel Blocker

CERA : Continue Erythropoesis Receptor Activator

CKD : Chronic Kidney Disease

COX : Cyclooxigenase

CVD : Cardiovascular Disease

dL : Desiliter

EPO : Erythropoetin

ESA : Erythropoesis Stimulating Agent

ESRD : End Stage Renal Disease

GGK : Gagal Ginjal Kronik

Hb : Hemoglobin

HCO3 : Biakrbonat

HDL : High Density Lipoprotein

IL 1β : Interleukin 1β

IL 2 : Interleukin 2

IL 6 : Interleukin 6

IMT : Indeks Massa Tubuh

LBP : Lipopolysaccaarida binding protein

LDL : Low Density Lipoprotein

LFG : Laju Filtrasi Glomerulus

LVH : Left Ventricular Hypertrophy

mmHg : Mili Meter Raksa

NaCl : Natrium Klorida

NSAID : Non Steroid Anti Inflamatory Drugs

NH3 : Nitrogen Hidroksida

NO : Nitric Oxide

xvii

NUD : Nitrogen Urea Darah

OAT : Obat Anti Hipertensi

PAF : Platelet Activating Factor

PJK : Penyakit Jamtung Koroner

PTH : Parathyroid Hormone

RAAS : Renin Angiotensin Aldosteron System

RMK : Rekam Medik Kesahatan

SIRS : Systemic Inflamatory Response Syndrome

TD : Tekanan Darah

TNF α : Tumor Necrosis Factor α

WBC : White Blood Cell

88

DAFTAR PUSTAKA

Abdullah, M. 2005. Kejadian Penyakit Jantung Di Indonesia. Available From :

http://www.fkm.undip.ac.id/data/index.php?action=4&idx=2701

Alam, S., and Hadibroto, I., 2007. Gagal Ginjal. Jakarta : Gramedia Pustaka

Utama

Amin, N., Mahmood R. T., Asad M. J., Zafar M., and Raja A. M. 2014.

Evaluating Urea and Creatinine Levels in Chronic Renal Failure Pre

and Post Dialysis: A Prospective Study. Available From :

http://researchpub.org/journal/jcvd/number/early/22.pdf

Anggraini, A. D., Waren, A. A., Situmorang, E., Asputra, H., and Siahaan, S.S.

2009. Faktor-Faktor yang Berhubungan dengan Kejadian Hipertensi

pada Pasien yang Berobat di Poliklinik Dewasa Puskesmas

Bangkinang Periode Januari sampai Juni 2008

Ando, K., Isshiki, M., and Takahashi, K., 2009. Effect of switching from

amlodipine to combination therapy with telmisartan and low-dose

hydrochlorothiazide. Available From : http://www.nature.com/hr/journal/

v32/n9/pdf/hr2009101a.pdf

Andany, M. M. A, Fernández, C. F., Bayolo, D. M., Quintela, E. C., and Montero,

A. D., 2014.Sodium Bicarbonate Therapy in Patients with Metabolic

Acidosis. Available From : http://www.hindawi.com/journals/tswj/2014/

627673/

Antman, E. M., 2007. Cardiovascular Therapeutics: A Companion to

Braunwald's Heart Disease. Philadelphia : Elsevier

Arcangelo, V. P., and Peterson, A. M., 2006. Pharmacotherapeutics for

Advanced Practice : A Practical Approach. Philadelphia : Lippincott

Williams & Wilkins

Arici, M., 2014. Management of Chronic Kidney Disease : A Clinicians

Guide. Heidelberg : Springer

89

Aronson, J. K., 2009. Meyler’s Side Effect of Cardiovascular Drug. United

Kingdom : Elsevier

Arora, P., Vasa, P., Brenner, D., Iglar, K., McFarlane, P., Morrison H., and

Badawi, A., 2013. Prevalence Estimates of Chronic Kidney Disease in

Canada: Results of a Nationally Representative Survey. Available

From : http://www.cmaj.ca/content/185/9/E417.full.pdf+html

Ayub. W., and Fletcher, S., 2000. End-stage Renal Disease and Erectile

Dysfunction. Is There any Hope? Available From : http://ndt.

oxfordjournals.org/content/15/10/1525.full.pdf+html

Asnelia, D., 2014. Hipertensi Krisis. Available From : http://cme.medicinus.co/

file.php/1/LEADING_ARTICLE_Hipertensi_Kritis.pdf

Aziza, L., 2007. Peran Antagonis Kalsium dalam Penatalaksanaan

Hipertensi. Available From : http://mki.idionline.org/index.php?uPage=

mki.mkidl&smod=mki&sp=public&key= MTM2LTE0

Baradero, M., Dayrit, M. W., and siswadi Y., 2005. Klien Gangguan Ginjal.

Jakarta : Penerbit Buku Kedokteran EGC

Basha, A., 2004. Hipertensi: Faktor Resiko Dan Penatalaksanaan. Available

From : http://www.pjnhk.go.id

Bianchi, S., Bigazzi, R., and Campese, V. E., 2006. Long-Term Effects of

Spironolactone on Proteinuria and Kidney Function in Patients with

Chronic Kidney Disease. Available Ftom : http://www.nature.com/

ki/journal/v70/n12/pdf/5001854a.pdf

Bijvank S. W., and Duvekot, J. J., 2010. Nicardipine for the Treatment of

Severe Hypertension in Pregnancy: A Review of the Literature.

Available From : http://academicdepartments.musc.edu/medicine/

divisions/pulmonary/fellowship_and_education/education/Critical%20Car

90

e%20Syllabus/critical_care_files/Obstetric%20Patients/nicardipine%2020

10.pdf

Bomback, A. S., and Bakris, G. L., 2011. Chronic Kidney Disease (CKD) and

Hypertension Essentials. Sudbury : Jones & Bartlett Learning

Braham-Grey, L., PhD, RD, CNSD; and Wiesen, K., MS, RD., 2004. A Clinical

Guide to Nutrition Care in Kidney Disease. US : American Dietetic

Association.

CDC, 2014. National Chronic Kidney Disease Fact Sheet 2014. Available From

: http://www.cdc.gov/diabetes/pubs/pdf/kidney_factsheet.pdf

Chandra, K. S., and Ramesh, G., 2013. The fourth-generation Calcium channel

blocker: Cilnidipine. Available From : http://www.ncbi.nlm.nih.gov/pmc/

articles/PMC3905258/pdf/main.pdf

Chen, W., and Abramowitz, M. K., 2014. Treatment of Metabolic Acidosis in

Patients With CKD. Available From : http://www.ncbi.nlm.nih.gov/pmc/

articles/PMC3946919/pdf/nihms514444.pdf

Chien, K., Chao, C., and Su, T., 2005. Bioavailability Study of Fixed-Dose

Tablet Versus Capsule Formulation of Amlodipine Plus Benazepril: A

Randomized, Single-Dose, Two-Sequence, Two-Period, Open-Label,

Crossover Study in Healthy Volunteers. Available From :

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964558/pdf/main.pdf

Chobanian, A.V., Bakris, G.L., Black, H.R., 2003. Seventh report of the Joint

National Committee on Prevention, Detection, Evaluation, and

Treatment of High Blood Pressure : Hypertension. Available From :

http://www.nhlbi.nih.gov/files/docs/guidelines/jnc7full.pdf

Cikrikcioglu, M.A., Karatoprak, C., Cakirca, M., Kiskac, M., Zorlu, M., Cetin, G.,

Yildiz, K., Erkoc, R., Alay, M., Erkal, S., Erkal, S.N., Dogan, S.,

Kazancioglu,R., 2013. Association of calcium channel blocker use with

lower hemoglobin levels in chronic kidney disease. Available From :

http://www.europeanreview.org/wp/wp-content/uploads/2530-2537.pdf

91

Corwin, E. J., 2001. Buku Saku Patofisiologi. Jakarta : Penerbit Buku

Kedokteran EGC

Cole, R. T., Kalogeropoulos, A. P., Georgiopoulou, V. V., Gheorghiade,

M., Quyyumi, A., Yancy, C., and Butler, J., 2011. Hydralazine and

Isosorbide Dinitrate in Heart Failure Historical Perspective,

Mechanisms, and Future Directions. Available From :

http://circ.ahajournals.org/content/123/21/2414.full.pdf+html

Dallas, M. E., 2015. A High Salt and Potassium Diet May Accelerate Chronic

Kidney Disease. Available From : https://www.nlm.nih.gov/medlineplus

/news/fullstory154687.html

Decker, S.B., Mueller, A.B, and Sowinski, M.K., 2007. Drug Dosing

Considerations in Alternative Hemodialysis. Available from :

http://www.ackdjournal.org/article/ S1548-5595(07)00048-1/fulltext

Depkes RI., 2006. Pharmaceutical Care untuk Penyakit Hipertensi. Jakarta :

Depkes RI

Duru, O. K., Li, S., Jurkovitz, C., Bakris, G., Brown, W., Chen, S., Collins, A.,

Klag, M., McCullough, M. A., McGill, J., Narva, A., Pergola, A., Singh,

A., and Norris, K., 2008. Race and Sex Differences in Hypertension

Control in CKD: Results From the Kidney Early Evaluation Program.

Available From : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866650/

pdf/nihms150995.pdf

Elliott, W., J., and Ram, C., V., S. 2011. Calcium Channel Blocker. Available

From : http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7176.2011.

00513.x/epdf

Frandsen, G., and Pennington, S. S., 2013. Abram’s Clinical Drug Therapy :

Rationales for Nursing Practice. Philadelphia : Wolters Kluwer

Frank, J., 2008. Managing Hypertension Using Combination Therapy.

Available From : http://www.aafp.org/afp/2008/0501/p1279.pdf

Frishman, W. H., Cheng-Lai, A., and Chen, J., 2005. Current Cardiovascular

Drugs. New York : Springer Science-Business Media

92

Goroll, A. H., and Mulley, A. G., 2011. Primary Care Medicine : Office

Evaluation and Management of The Adult Patient, Sixth Edition.

Philadelphia : Lippincott Williams & Wilkins

Gradman, A. H., Basile, J. N., Carter, B. L., and Bakris, G. L., 2010.

Combination Therapy in Hypertension. Available From :

http://www.ashjournal.com/article/S1933-1711(10)00006-9/pdf

Gray, L. D. B., Burrowes, J. D., and Chertow, G. M., 2008. Nutrition in Kidney

Disease. Totowa : Humana Press

Grove, E. L., 2012. Antiplatelet Effect Of Aspirin In Patients With Coronary

Artery Disease. Available From : http://www.danmedj.dk/portal/pls/

portal/!PORTAL.wwpob_page.show?_docname=9206964.PDF

Gunawan, L., 2001. Hipertensi : Tekanan Darah Tinggi. Yogyakarta :

Percetakan Kanisus.

Guyton, A.C., and Hall John E., 2006. Textbook of Medical Physiology.

Philadelphia : Elsevier.

Hajjar, I., MD, MS; dan Kotchen, T.A., MD., 2000. Trends in Prevalence,

Awareness, Treatment, and Control of Hypertension in the United

States, 1988-2000.

Haller, H., 2008. Effective management of hypertension with dihydropyridine

calcium channel blocker-based combination therapy in patients at

high cardiovascular risk. Available From : http://www.ncbi.nlm.nih.gov/

pmc/articles/PMC2324209/

Hsieh, M. F., Wu, I. W., Lee, C. C.,Wang, S. Y., Wu, M. S. 2010. Higher Serum

Potassium Level Associated with Late Stage Chronic Kidney Disease.

Available From : http://memo.cgu.edu.tw/cgmj/3404/340411.pdf

Hughes, S. C., Levinson, G., and Rosen, M. A., 2002. Shinder and Levinson’s

Anasthesia for Obstretrics. Philadelphia : Lippincott Williams & Wilkins

Hunts, W. A., 2011. Kidney Disease : A Guide For Living. Maryland : The

Johns Hopkins Unisersity Press

93

Iacobellis, G., 2006. Drug- Drug Interactions In The Metabolic Syndrome.

New York : Nova Science Publishers Inc

IAI, 2013. Informasi Spesialite Obat Indonesia Vol. 48. Jakarta : PT. ISFI

Penerbitan

Ismudiati, L., 2003. Buku Ajar Kardiologi. Jakarta : Balai Penerbit Fakultas

Kedokteran Universitas Indonesia

JNC7, 2003.Prevention, Detection, Evaluation, and Treatment of High Blood

Pressure. Available From :https://www.nhlbi.nih.gov/files/docs/

guidelines/express.pdf

Johnson, D., 2012. Diagnosis, Classification, and Staging of Chronic Kidney

Disease. Available From : http://www.cari.org.au/CKD/CKD%20early/

Diag_Classification_Staging_ECKD.pdf

Kalra, S., Kalra, B., and Agrawal, N., 2010. Combination Therapy in

Hypertension: An update. Available From : http://link.springer.com/

article/10.1186/1758-5996-2-44

Kasper, D. L., Fauci, A. S., Longo, D. N., Braunwald. E., Hauser, S., and

Jameson, J. L., 2012.Harrison’s Principles of Internal Medicine. Ed 18.

New York: Mc-Graw Hill

KDIGO, 2012. Clinical Practice Guideline for the Evaluation and

Management of Chronic Kidney Disease. Available From :

http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_201

2_CKD_GL.pdf

Kizilirmak, P., Uresin Y., and Yildiz, O. B., 2012. The Efficacy and Safety of

Triple vs Dual Combination of Angiotensin II Receptor Blocker and

Calcium Channel Blocker and Diuretic: A Systematic Review and

Meta-Analysis. Available From : http://onlinelibrary.wiley.com/doi/

10.1111/jch.12040/full

94

Kovesdy, C. P., 2012. Metabolic Acidosis and Kidney Disease: Does

Bicarbonate Therapy Slow The Progression ff CKD. Available From :

http://ndt.oxfordjournals.org/content/27/8/3056.full.pdf+html

Kresnawan T., 2012. Diet Rendah Protein Dan Penggunaan Protein Nabati

Pada Penyakit Ginjal Kronik. Available From : http://gizi.depkes.go.id/

wp-content/uploads/2012/05/diet_rendah_prot-nabati.pdf

Krummel, D. A., 2004. Medical Nutrition Therapy in Cardiovascular Disease.

USA: Saunders co

Langman, C. B., and Cannata-Andia, J. B. 2010. Calcium in Chronic Kidney

Disease: Myths and Realities. Available From : http://cjasn.asnjournals.

org/content/5/Supplement_1/S1.full.pdf+html

Levey, A. S., Coresh, J., Balk, E., Kausz, A. T., Levin, A., Steffes, M. W., Hogg,

R. J., Perrone, R. D., Lau, J., and Eknoyan G., 2003. National Kidney

Foundation Practice Guidelines for Chronic Kidney Disease:

Evaluation, Classification, and Stratification. Available From :

http://annals.org/data/Journals/AIM/20044/0000605-200307150-00013.pdf

Lerma, E. V., 2013. Clinical Decision in Nephrology, Hypertension, and

Kidney Disease Transplantation. New York : Springer.

Lipowsky, R., Richter, D., and Kremer, K., 2013. The Structure and

Conformation of Amphiphilic Membranes : Proceedings of The

International Workshop. Berlin : Springer-Verlag

Lydtin, H., and Trenkwalder, P., 2002. Calcium Antagonist : A Critical

Review.Heidelberg : Springer-Verlag

Lopez-Novoa, J. M., Martinez-Salgado, C., Rodriguez-Pena, A. B., and

Hernandez, F. J. L., 2010. Common Pathophysiological Mechanism of

Chronic Kidney Disease : Therapeutic Perspectives. Available From :

https://www.researchgate.net/profile/Jose_LopezNovoa/publication/45091

427_Common_pathophysiological_mechanisms_of_chronic_kidney_disea

se_therapeutic_perspectives/links/0fcfd5062f18813c83000000.pdf

95

Lukela, J. R., Harrison, R. V., Jimbo, M., Mahallati, A., Saran, R., and Sy, A. Z.,

2014. Guidelines for Clinical Care Ambulatory : Management of

Chronic Kidney Disease. Available From : http://www.med.umich.edu/

1info/FHP/practiceguides/kidney/CKD.pdf

Mallat, S. G., 2012. What is a preferred angiotensin II receptor blocker-based

combination therapy for blood pressure control in hypertensive

patients with diabetic and non-diabetic renal impairment. Available

From : http://www.cardiab.com/content/pdf/1475-2840-11-32.pdf

Mahesa, D. R., 2010. Penyakit Ginjal Kronis (Chronic Kidney Disease).

Available From : http://pustaka.unpad.ac.id/wp-content/uploads/2014/01/

pustaka_unpad_penyakit_ginjal_kronis.pdf

Maria, G., Puspita, R. D., and Sulistyowati, Y., 2012. Hubungan Asupan

Natrium Dan Kalium Dengan Tekanan Darah Pada Pasien Hipertensi

Di Unit Rawat Jalan Di Rumah Sakit Guido Valadares Dili Timor

Leste. Available From : http://journal.respati.ac.id/index.php/medika/

article/viewFile/73/69

Marliani, L., and Tantan, S., 2007. 100 Question & Answer Hipertensi. Jakarta :

Elex Media Komputindo

Martin, J., 2008. Hypertension Guidelines: Revisiting the JNC 7

Recommendations. Available From : http://www.jlgh.org/JLGH/media/

Journal-LGH-Media-Library/Past%20Issues/Volume%203%20-%20Issue

%203/JLGH_V3n3_p91-97.pdf

McPhee, S. J., Lingappa, V. R., and Ganong, W. F., 2003 Pathophysiology of

Disease: An Introduction to Clinical Medicine. Lange.

Ministry of Health and Kidney Health, 2014. Living with Kidney Disease : a

Comprehensive Guide For Coping With Chronic Kidney Disease,

Second Edition. Available From : https://www.health.govt.nz/system/

files/documents/publications/living-with-kidney-disease-2nd-ed-dec14.pdf

96

Miyagawa, K., Dohi, Y., Nakazawa, A., Sugiura, T., Yamashita. S., Sato,

K., Kimura, G., 2010. Renoprotective effect of calcium channel

blockers in combination with an angiotensin receptor blocker in

elderly patients with hypertension. A randomized crossover trial

between benidipine and amlodipine.Available From :

http://www.tandfonline.com/doi/full/10.3109/10641960902929446

Moini, J., 2015. The Pharmacy Technician : A Comprehensive Approach,

Third Edition. Boston : Cengange Learning

Moorthy, A. V., Becker, B. N., and Djamali A., 2009. Pathophysiology of

Kidney Disease and Hypertension. Philadelphia : Elsevier

Muchtar, N.R., Tjitrosantoso, H., Bodhi, W., 2015. Studi Penggunaan Obat

Antihipertensi Pada Pasien Gagal Ginjal Kronik Yang Menjalani

Perawatan Di Rsup Prof. Dr. R. D. Kandou Manado Periode Juli 2013

- Juni 2014. Available From : http://ejournal.unsrat.ac.id/index.php/

pharmacon/article/viewFile/8833/8392

Muhammadun, 2010. Hidup Bersama Hipertensi Seringai Darah Tinggi Sang

Pembunuh Sejati. Jokjakarta: In-Books

Nahas, M. E., and Levin, A., 2009. Chronic Kidney Disease : A Practical Guide

to Understanding and Management. New York : Oxford University

Press

Neliya, S. W., 2012. Hubungan Pengetahuan tentang Asupan Cairan dan

Cara pengendalian Asupan cairan terhadap Penambahan Berat

Badan. Jurnal Nursing Studies. Available From : http://repository.unri.

ac.id/handle/123456789/1872

Nephrol, I. J., 2005. Clinical practice guidelines on hypertension and

antihypertensive agents in chronic kidney disease (CKD). Available

From : http://medind.nic.in/iav /t05/s1/iavt05s1p14.pdf

97

NKF, 2010. 2010 Annual Report : 60 years of Fighting Kidney Disease.

Availbale From : https://www.kidney.org/sites/default/files/docs/annual_

report_2010.pdf

Nurjanah, A., 2012. Hubungan Antara Lama Hipertensi Dengan Angka

Kejadian Gagal Ginjal Terminal Di Rsud Dr. Moewardi Surakarta.

Availabale From : http://eprints.ums.ac.id/23959/10/NASKAH

PUBLIKASI.pdf

O’Mara, N. B. 2008. Anemia in Patients With Chronic Kidney Disease.

Available From : http://spectrum.diabetesjournals.org/content/21/1/12.full.

pdf

Opie, L. H., 2012. Clinical Use of Calcium Channel Antagonist Drugs.

Massachusetts : Kluwer Academic Publisher

Opie, L. H., and Gersh, B. J., 2013. Drug for The Heart, Eighth Edition.

Philadelphia : Elsevier Saunders

Opler, L. A., 2005. The Complete Pill Guide, Second Edition. New York :

Barnes & Noble Books

Owen, J., 2003. Drug Information Reference, 5th Edition. Available From :

http://dpic.org /sites/default/files/pdf/ DIR_CCBs.pdf

Panggabean, M. M., 2006. Penyakit Jantung Hipertensi. Buku Ajar Ilmu

Penyakit Dalam. Jilid 3. Edisi IV. Jakarta: Pusat Penerbitan Departemen

Ilmu Penyakit Dalam FK UI.

Papadopoulou, E., Varaouktsi, A., Lazaridis, A., Boutari, C., and Doumas M.,

2015. Erectile Dysfunction in Chronic Kidney Disease: From

Pathophysiology to Management. Available From : http://www.ncbi.

nlm.nih.gov/pmc/articles/PMC4491929/pdf/WJN-4-379.pdf

Pardo, M., and Sonner, J. M., 2007. Mannual of Anasthesia Practice. New York

: Cambridge University Press

98

Pearce, E. C., 2009. Anatomi dan Fisiologi untuk Paramedis. Jakarta : PT.

Gramedia

Perez-Lopez, F. R., Larrad-mur, L., Kallen, A., Chedraui, P., and Taylor, H. S.,

2010. Gender Differences in Cardiovascular Disease: Hormonal and

Biochemical Influences. Available From : http://www.ncbi.nlm.nih.gov/

pmc/articles/PMC3107852/pdf/nihms-293590.pdf

Pernefri, 2011. 4th Annual Report of Indonesian Renal Registry. Available

From :http://www.pernefri-inasn.org/Laporan/4th%20Annual%20Report

%20Of%20IRR%202011.pdf

Phoon, R. K., 2012. Chronic Kidney Disease in The Elderly Assessment and

Management. Available From : http://www.racgp.org.au/download/

Documents/AFP/2012/December/201212phoon.pdf

Price, S., and Wilson L., 2005. Patofisiologi : Konsep Klinis Proses-Proses

Penyakit. Jakarta : EGC

Rahajeng, E., dan Tuminah, S., 2009. Prevalensi Hipertensi dan

Determinannya di Indonesia. Jakarta: Pusat Penelitian Biomedis dan

Farmasi Badan. Penelitian Kesehatan Departemen Kesehatan RI.

Rohaendi. 2008. Treatment Of High Blood Pressure. Jakarta :Gramedia Pustaka

Utama

Rimoldi, S. F., Messerli, F. H., Chavez, P., Stefanini, G. G., and Scherrer, U.,

2015. Efficacy and Safety of Calcium Channel Blocker/Diuretics

Combination Therapy in Hypertensive Patients: A Meta-Analysis.

Available From : http://onlinelibrary.wiley.com/doi/10.1111/jch.12462/pdf

Rossi, S., 2006. Australian Medicines Handbook 2006 Ed. Adelaide: Australian

Medicines Handbook Pty Ltd.

Sarnak, M. J., 2003. Cardiovascular Complications in Chronic Kidney

Disease. Available From : http://www.ajkd.org/article/S0272-

6386(03)00372-X/pdf

99

Sarwanto, Wilujeng, L. K., Rukmini, 2007. Prevalensi Penyakit Hipertensi

Penduduk Di Indonesia Dan Faktor Yang Berisiko. Available From :

http://download. portalgaruda.org/article.php?article=80593&val=4892

Schrier, R. W., 2009. Mannual of Nephrology Seven Edition. Philadelphia :

Lippincott Williams & Wilkins

Segura, J., Garcı´a-Donaire, J. A., and Ruilope, L. M., 2006. Calcium Channel

Blockers and Renal Protection: Insights from the Latest Clinical

Trials.Available From : http://jasn.asnjournals.org/content/16/3_suppl_1/

S64.full.pdf

Sever, V. S., and Messerli, F. H., 2011. Hypertension Management 2011:

Optimal Combination Therapy. Available From : http://eurheartj.

oxfordjournals.org/content/32/20/2499.full.pdf

Sheps, 2005. Mayo Klinik Hipertensi. Mengatasi Tekanan Darah Tinggi.

Jakarta: PT Intisari Mediatama

Sherwood, L., 2001. Fisiologi Manusia : dari Sel ke Sistem, Edisi 2. Jakarta :

EGC

Smeltzer, S. C., and Bare, B. G., 2001. Buku Ajar Keperawatan Medikal

Bedah. Jakarta : EGC

Soenarta, A. A., Erwinanto, Mumpuni A. S. S., Barack R., Lukito A. A.,

Hersunarti N., dan Pratikto R. S., 2015. Pedoman Tatalaksana

Hipertensi Pada Penyakit Kardiovaskular. Available From

:http://www.inaheart.org/upload/file/Pedoman_TataLaksna_hipertensi_pad

a_penyakit_Kardiovaskular_2015.pdf

Spasovski, G.,Massy, Z., and Vanholder R. 2009. Phosphate Metabolism in

Chronic Kidney Disease: From Pathophysiology to Clinical

Management. Available From : http://www.mmh.org.tw/taitam/

kid_int/Blog/Entries/2009/12/14_Dec_2009_Schedule_files/Phosphate_M

etabolism_in_Chronic_Kidney_Disease.pdf

100

Sukandar, E., 2006. Neurologi Klinik : Edisi ketiga. Bandung: Pusat Informasi

Ilmiah (PII) Bagian Ilmu Penyakit Dalam Fakultas Kedokteran UNPAD.

Sullivan, K., 2013. 2013 Nurse’s Drug Handbook, Twelfth Edition. Burlington

: Jones & Bartlett Learning

Sustrani, L., 2006. Hipertensi. Jakarta : GramediaPustaka.

Suyono, S., 2004. Patofisiologi Diabetes Mellitus : Pnatalaksanaan DM

Terpadu. Jakarta : Balai Penerbit FKUI

Suwitra, K., 2006. Gagal Ginjal Kronik Buku Ajar Ilmu Penyakit Dalam Jilid

1 Edisi ke-4. Jakarta: Balai pustaka FK UI.

Sweetman, S. C., 2009. Martindale 36 : The Complete Drug Reference.

London : Pharmaceutical Press

Syamsir, A., and Iwan, H., 2007. Gagal Ginjal. Jakarta : Gramedia Pustaka

Utama

Tatro, D. S., 2003. A to Z Drug Facts. San Francisco : Facts and Comparisons

Thomas, R., Kanso, A., and Sedor, J. R., 2008. Chronic Kidney Disease and Its

Complications. Available From : http://www.ncbi.nlm.nih.gov/pmc/

articles/PMC2474786/pdf/nihms54692.pdf

Tilley, L. P., 2008. Manual of Canine and Feline Cardiology, Fouth

Edition.United Kingdom : Elsevier

Toal, C. B., Meredith, P. A., Elliott, H. L., 2012. Long-Acting Dihydropyridine

Calcium-Channel Blockers and Sympathetic Nervous System Activity

in Hypertension: A Literature Review Comparing Amlodipine and

Nifedipine GITS. Available From : http://www.ncbi.nlm.nih.gov/pmc/

articles/PMC3469239/pdf/sblo21-3.pdf

Tobias, J. D., Tulman, D. B., and Bergese, S. D., 2013. Clevidipine for

Perioperative Blood Pressure Control in Infantsand Children.

Available From : http://www.mdpi.com/1424-8247/6/1/70/pdf

101

Toth-Manikowski, S., and Atta, M. G., 2015. Diabetic Kidney Disease:

Pathophysiology and Therapeutic Targets. Available From :

http://www.hindawi.com/journals/jdr/2015/697010/

Tzanakaki, E., Boudouri, V., Stavropoulou, A., Stylianou, K., Rovithis, M., dan

Zidianakis, Z., 2014. Causes and Complications of Chronic Kidney

Disease in Patients on Dialysis. Available From : http://www.hsj.gr/

medicine/causes-and-complications-of-chronic-kidney-disease-in-patients-

on-dialysis.pdf

Vikrant, S., and Tiwari, S. C., 2001. Essential Hypertension – Pathogenesis and

Pathophysiology. Available From : http://medind.nic.in/jac/t01/i3/jact01i3

p140.pdf

Wade, A Hwheir, D N Cameron, A. 2003. Using a Problem Detection Study

(PDS) to Identify and Compare Health Care Privider and Consumer

Views of Antihypertensive therapy. Journal of Human Hypertension.

Available From : http://www.nature.com/jhh/journal/v17/n6/full/1001565

a.html

Walker, R., and Whittlesea, C., 2012. Clinical Pharmacy and Terapeutics.

London : Elsivier.

Walt, I., Swanepoel, C. R., Mahala B., and Meyers, A. M., 2015. Important

Complications of Chronic Kidney Disease. Available From :

http://www.samj.org.za/index.php/samj/article/view/9536/6646

Wan, X., Ma, P., and Zhang, X. 2013. A promising choice in hypertension

treatment: Fixed-dose combinations. Available From : http://www.

sciencedirect.com/science/article/pii/S1818087613000810

Wearns, B., 2007. Chronic Kidney Disease Prevalence Modelling Briefing

Document. UK: Associated People Health Observatorium.

Weber, M. A., Schiffrin, E. L., White, W. B., Mann, S., Lindholm, L. H.,

Kenerson, J. G., Flack, J. M., Carter, B. L., Materson, B. J., Ram, V. S.,

Cohen, D. L., Cadet, J. C., Jean-Charles, R. R., Taler, S., Kountz, D.,

102

Townsend, R. R., Chalmers, J., Ramirez, A. J., Bakris, G. L., Wang, J.,

Schutte, A. E., Bisognano, J. D., Touyz, R. M., Sica, D., and Harrap, S. B.,

2014. Clinical Practice Guidelines for the Management of

Hypertension in the Community A Statement by the American Society

of Hypertension and the International Society of Hypertension.

Available From : http://csc.cma.org.cn/attachment/2014315/1394885445

745.pdf

Weir, M.R., and Dworkin, L.D., 2000. Antihypertensive drugs, dietary salt,

and renal protection: How low should you go and with which therapy.

Baltimore : Department of Medicine, University of Maryland School

of Medicine. Available From :http://www.ajkd.org/article/S0272-

6386(98)00173-5/fulltext

Wilkerson, J. A., 2010. Medicine for Mountaineering & Other Wilderness

Activities. Seattle : The Mountaineers Books