Download - Penatalaksanaan
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Kolesterol Total<200
200-239
≥240
Optimal
Diinginkan
Tinggi
Kolesterol LDL<100
100-129
130-159
160-189
≥190
Optimal
Mendekati optimal
Diinginkan
Tinggi
Sangat Tinggi
Kolesterol HDL <40
≥60
Rendah
Tinggi
Trigliserida
<150
150-199
200-499
≥500
Optimal
Diinginkan
Tinggi
Sangat Tinggi
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FAKTOR RISIKOFAKTOR RISIKOFaktor risiko (selain Kolesterol LDL) yang
menentukan sasaran kolesterol LDL yang ingin dicapai
• Umur pria ≥45 tahun dan wanita ≥ 55 tahun• Riwayat keluarga PAK dini • Kebiasaan merokok• Hipertensi (≥ 140/90 mmHg atau sedang mendapat
obat hipertensi ).• Kolesterol HDL rendah ( < 40 mmHg )
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Tiga kelompok risiko PAKTiga kelompok risiko PAKKategori Risiko Sasaran kolesterol LDL
(mg/dl)Risiko Tinggi :
• Mempunyai riwayat PAK
• Mereka yang disamakan dengan PAK :
– Diabetes mellitus
– bentuk lain penyakit aterosklerotik : stroke, penyakit arteri perifer, aneurisma.
–Faktor resiko multipel (> 2 risiko ) yang diperkirakan dalam kurun waktu 10 tahun mempunyai risiko PAK ≥ 20%
Risiko Sedang ( ≥ 2 faktor risiko )
Risiko Rendah ( 0-1 faktor risiko )
< 100
<130
<160
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PENATALAKSANAAN
• Penatalaksanaan Non-farmakologis– Perubahan gaya hidup– Aktivitas fisik; olahraga 3-5 x/minggu, selama 45-60 menit– Menghentikan merokok– Menurunkan berat badan bagi yang gemuk– Bila trigliserida tinggi
• Mengurangi asupan alkohol, karbohidrat dan lemak– Bila Kolesterol LDL dan kolesterol total tinggi
• Mengurangi asupan lemak total dan jenuh (Saturated Fatty Acid=SAFA)
• Meningkatkan asupan lemak tidak jenuh rantai tunggal dan ganda (Mono dan Poly Unsaturated Fatty Acid)
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PENATALAKSANAAN
• Penatalaksanaan Farmakologis– Setelah 6 minggu terapi non farmakologis,
dilakukan evaluasi ulang. Bila belum mencapai sasaran harus diberikan terapi farmakologis
– Setiap 4-6 bulan dilakukan evaluasi
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TERAPI FARMAKOLOGIS
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STATIN
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STATIN
Cara Kerja : • Obat ini bekerja dengan mencegah kerja enzim
HMG-CoA reductase yaitu suatu enzim di hati yang berperan pada sintesis kolesterol.
• Dengan menurunnya sintesis kolesterol di hati akan menurunkan sintesis Apo B-100
• Selain itu meningkatkan reseptor LDL di hati, sehingga kadar kolesterol-LDL darah akan ditarik ke hati, yang akan menurunkan kadar kolesterol LDL dan juga VLDL
• Juga dapat menurunkan kadar trigliserida
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AcetylCoA
HMG-CoA
Mevalonate Farnesylpyrophosphat
e
Squalene Cholesterol
Squalenesynthase
DolicholHMG-CoAreductase
Rasprotein
Farnesyl-transferase
Farnesylatedproteins
E,E,E-Geranylgeranylpyrophosphate
Geranylgeranylatedproteins
Ubiquinones
Cholesterol Biosynthetic Pathway
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LDLLDLReceptorReceptorLDLLDLReceptorReceptor
Statins
Acetate
LDLLDLLDLLDL
HMG-CoAReductase
Cholesterol
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Cholesterol Absorption Inhibitors
• Inhibit absorption of dietary cholesterol
• Inhibit reabsorption of biliary cholesterol
• Lower LDL cholesterol
Mechanism: Mechanism: Inhibit LDL FormationInhibit LDL Formation
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Inhibitors of Cholesterol Synthesis
• Inhibit synthesis of cholesterol by cells
• Lower LDL cholesterol
Mechanism: Promote LDL Clearance
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STATINHMG CoA Reductase inhibitor
• Telah dipasarkan 6 jenis :» Lovastatin» Simvastatin» Pravastatin» Fluvastatin» Atorvastatin» Rosuvastatin
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STATINHMG CoA Reductase inhibitor
• Efek Samping :– Miositis– Rhabdomyolisis– Gangguan fungsi hati
• Dosis :– Lovastatin 10-80mg/dl– Pravastatin 10-40mg/dl– Simvstatin 5-40 mg/dl– Fluvastatin 20-40 mg/dl– Atorvastatin 10-80 mg/dl– Rosuvastatin 10-20 mg
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EZETIMIBE
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Ezetimibe
• Cara kerja : ↓ absorbsi kolesterol di usus halus → ↓ LDL 16-18%.
• Efek Samping :– Sakit kepala, nyeri perut, dan diare
• Dosis : 10 mg/hari.
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LymphLymphLymphLymph EnterocyteEnterocyteEnterocyteEnterocyte IntestinalIntestinalLumenLumenIntestinalIntestinalLumenLumen
Ezetimibe
Cholesterol
NPC1L1
CholesterylEster ABCG5/G8
ACAT
Ezetimibe
XX
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LymphLymphLymphLymph EnterocyteEnterocyteEnterocyteEnterocyte IntestinalIntestinalLumenLumenIntestinalIntestinalLumenLumen
Cholesterol Absorption Inhibitors
CholesterylEster
CMapoB48
Triglyceride
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Cholesterol Absorption Inhibitors
DuodenumDuodenumDuodenumDuodenum
JejunumJejunumJejunumJejunum
IleumIleumIleumIleum
CMapoB48
Liver
CM RemnantapoB48
VLDLapoB100
EzetimibeXX
LDLapoB100
ColonColon
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Assembly and Secretion of VLDL
Presence of TriglyceridesPresence of Triglycerides
ApoB
MTPMTP
Cholesteryl Esters
Cholesterol
Dietary/Biliary Synthesis
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Effect of Cholesterol Absorption Inhibitor
Presence of TriglyceridesPresence of Triglycerides
ApoB
Cholesterol
Dietary/Biliary Synthesis
Ezetimibe XX
MTPMTP
Cholesteryl Esters
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Adding a Statin Blocks Compensatory Increase in Synthesis
Presence of TriglyceridesPresence of Triglycerides
ApoB
Cholesterol
Dietary/Biliary Synthesis
Ezetimibe XX XX Statin
MTPMTP
Cholesteryl Esters
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Ezetimibe
• Kombinasi simvastatin dengan ezetimibe yaitu vytorin, ternyata mempunyai efek lebih baik dibandingkan dengan simvastatin dosis tunggal
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Dual Inhibition
DuodenumDuodenum
JejunumJejunum
IleumIleum
CMapoB48
Liver
CM RemnantapoB48
VLDLapoB100
EzetimibeXX
LDLapoB100
XXStatinStatin
ColonColon
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BILE SEQUSTERING AGENT
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Bile sequestering agents
• Recycling of Bile Acids: Enterohepatic circulation– 98% recycling of bile
acids
• Cholestyramine Treatment– Resin binds bile acids– Prevents recycling– Increased uptake of LDL-
C for bile acid synthesis
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Bile sequestering agents
• Bile acid sequestrants– Reduces LDL by 15-30%– Side effects: GI distress, constipation,
decreased absorption of other drugs
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• Bile sequestering agents
Bile sequestering agents
Bileacids
liver
Bile acids
95 % reabsorbed
5% in feces
NH3+
NH3+
1. Bind bile acid2. Utilize more cholesterol to make bile acids>10% in feces
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ASAM FIBRAT
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Derivat Asam Fibrat
• Cara Kerja : Meningkatkan reverse cholesterol transport melalui aktivasi peroxisome proliferator-activated receptor-α (PPR-α), dengan cara:– Meningkatkan pembentukan apo A-1 dan apo A-2 di hati
sehingga sintesis HDL meningkat
– Mengaktifkan SR-B1 sehingga dapat lebih aktif menjaring kolesterol HDL
– Mengaktifkan ABC-1 sehingga HDL lebih cepat mengankut kolesterol bebas dari makrofag menuju tepi sel, kemudian diangkut oleh HDL nascent
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Derivat Asam Fibrat
• Cara Kerja : – Mengaktifkan enzim lipoprotein lipase di hati yang kerjanya
memecah trigliserid, sehingga menurunkan sintesis trigliserid di hati dan menurunkan kadar trigliserid plasma
• Terdapat 4 jenis : • Gemfibrozil: 600-1200mg• Bezafibrat• Ciprofibrat• Fenofibrat: 160 mg
• Efek Samping : Mual, gangguan fungsi hati, miositis• Apabila kadar trigliserid sudah turun dan kadar kolesterol LDL
belum mencapai sasaran maka dapat diberikan pengobatan kombinasi dengan HMG Co-A reductase inhibitor.
• Kombinasi tersebut sebaiknya dipilih asam fibrat fenofibrat.
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Fibric Acid
• Fibric Acids– Decreases LDL by 5-20%
• Larger decreases in TG (20-50%), increases HDL– Mechanism of action: increases LPL activity– Side effects: dyspepsia, myopathy, gallstones
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ASAM NIKOTINIK
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Asam Nikotinik
• Cara kerja : – diduga bekerja menghambat enzim hormone sensitive
lipase di jaringan adiposa, dengan demikian akan mengurangi jumlah asam lemak bebas.
• Diketahui bahwa asam lemak bebas ada dalam darah sebagian akan ditangkap oleh hati dan akan menjadi sumber pembentukan VLDL.
• Dengan menurunnya sintesis VLDL di hati, akan mengakibatkan penurunan kadar trigliserid, dan juga kolesterol LDL di plasma, maka disebut juga sebagai broad spectrum lipid lowering agent
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Asam Nikotinik
• Dosis– Untuk mencegah efek samping penggunaan asam nikotinik
sebaiknya dimulai dengan dosis rendah kemudian ditingkatkan, misalnya selama satu minggu 375 mg/hari kemudian ditingkatkan secara bertahap sampai mencapai dosis maksimal sekitar 1500-2000 mg/hari
• Efek Samping : – Flushing : yaitu perasaan panas pada muka bahkan di
badan– Takikardi– Gatal, mual, diare, hiperurisemia, ulkus peptik– Intoleransi glukosa– Gangguan fungsi hati.
• Hasil yang sangat baik didapatkan bila dikombinasikan dengan golongan HMG-CoA reductase inhibitor.
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Niacin
• Pharmacological doses of niacin– 5-25% reduction in LDL
• Increases HDL, decreases LDL– Proposed mechanism
• Reduces VLDL synthesis• Decreases lipolysis in adipose• Increases LPL activity• Decreases esterification of TG in liver
– Side effects: flushing, GI distress, hyperglycemia, hyperuricemia, hepatotoxicity
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KESIMPULAN
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EFEK OBAT TERHADAP KADAR LIPID SERUM
OBAT KOL LDL KOL HDL TG
STATIN ↓ 18 - 55 % ↑ 5 - 15 % ↓ 7 - 30 %
RESIN ↓ 15 - 30 % ↑ 3 - 5 % (-) / ↑
FIBRAT ↓ 5 - 25 % ↑ 10 - 20 % ↓ 20 - 50 %
ASAM NIKOTINAT ↓ 5 - 25 % ↑ 15 - 35 % ↓ 20 - 50 %
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Pilihan obat hipolipidemik sesuai jenis dislipidemia
DISLIPIDEMIA OBAT
HIPERKOLESTEROLEMIA Statin ± Resin
DISLIPIDEMIA CAMPURAN
Statin ± Fibrat/Asam nikotinat
HIPERTRIGLISERIDEMIA Fibrat/Asam nikotinat
ISOLATED LOW-HDL-CHOLESTEROL Fibrat/Asam nikotinat
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Risiko sedang
Kol-LDL ≥ 130mg/dl
Diet, dan olahragaPertimbangkan pemb. statin
Periksa ulang 3 bulan
Jika tetap tinggiTeruskan pemberian Statin atau tambah gol lain
Periksa ulang 3 bulan
Sasaran kol-LDL < 130 mg/dl
PENATALAKSANAAN DISLIPIDEMIA PADA PASIEN
RISIKO SEDANG
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Terapi Terapi
Terapi diet Periksa ulang 4-6 minggu
Kol-LDL < 100 mg/dl Kol-LDL ≥ 100mg/dl
•Diet, olahraga•Mulai statin
•Periksa ulang 3 bulan
•Teruskan diet, olah raga•Periksa ulang 6-12 bulan
Sasaran Kol- LDL < 100 mg/dl
PENATALAKSANAAN DISLIPIDEMIA PADA PASIEN
RISIKO TINGGI
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Terapi Terapi Mulai dengan statin/resin/asam nikotinat (6 minggu)
Kol-LDL < 100 mg/dl Kol-LDL ≥ 100mg/dl
•Tingkatkan dosis statin atau•Tambah dengan resin/asam nikotinat
•Periksa ulang 3 bulan
•Teruskan statin selama 3 bulan •Diet, olah raga
•Periksa ulang 3 bulan
Sasaran Kol- LDL < 100 mg/dl
PENATALAKSANAAN OBAT HIPOLIPIDEMIK PADA PASIEN PJK