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HIPERLIPOPROTEINEMIA
Dra. Fita Rahmawati, Sp.FRS, Apt
Objectives
DEFINISI
HIPERLIPIDEMIA :PENINGKATAN KADAR LIPID PLASMA
DARAH KOLESTEROL DAN ATAU TRIGLISERIDA
HIPERLIPOPROTEINEMIA : PENINGKATAN KADAR
MAKROMOLEKUL LIPOPROTEIN YANG MENGANDUNG
LIPID DALAM PLASMA
PENTING --- HYPERKOLESTEROL, HDL RENDAH DAN
TERUTAMA PENINGKATAN LDL BERHUBUNGAN DENGAN
PENYAKIT JANTUNG KORONER (PJK) DAN
CEREBROVASCULAR MORBIDITY DAN MORTALITY
PENURUNAN KOLESTEROL MENURUNKAN PENYAKIT
KORONER 20 %
Triglycerides
Cholesterol
Phosospholipids/
Lechitin
LIPOPROTEIN
chylomicrons
STRUKTUR LIPOPROTEIN
PATOPHYSIOLOGY
PENYEBAB HIPERLIPIDEMIA
1. PRIMER (MONOGENIK) KETURUNAN/GENETIK
The primary defect in familial hypercholesterolemia is the
inability to bind LDL to the LDL receptor (LDL-R)
2. SEKUNDER/POLIGENIK/MULTIFAKTORIAL
PENYAKIT LAIN : DM, HIPERTIROID
DIET : ALKOHOL , MEROKOK
OBAT-OBATAN : TIAZID, ESTROGEN
Kolesterol
Trigliserid
HDL
Tiazid
5 10 %
30 50 %
10 20 G/L
B-bloker
Tetap
15 50 %
5 15 %
Prazozin
09%
0 16 %
0 17 %
Estrogen
5%
40 60 %
Cyklospori
15 20 %
Tetap
Captopril
Tetap
Tetap
Methyldopa
5 10 %
0 25 %
Tetap
Tetap
JENIS-JENIS LIPOPROTEIN :
KILOMIKRON
VLDL (VERY LOW DENSITY LIPOPROTEIN)
IDL (BENTUK ANTARA VLDL MJD LDL)
LDL (LOW DENSITY LIPOPROTEIN)
HDL UNTUK BERSIHAN TRIGLISERIDA DAN
KOLESTEROL.
JUMLAHNYA MENURUN PADA
PENDERITA GEMUK, PEROKOK, DM
Lipid metabolisme
UPTAKE
Fats from the diet are cleaved by gastric lipase
Solibilized in the gut by bile acids
The emulsified complexes enter the gut mucosa
and are packaged into chylomicrons
They are transported in the lymph then the blood
Chylomicron are substrates for lipoprotein lipase
(LPL, liberating triflycerides) in endothelial cells,
fat cells, muscle and the liver, leaving chylomicron
remnants
Fats are released that are taken up by cells
REPACKING
The liver libetrates lipids from chylomicron
remnants and repackages then into lipoproteins.
Triglycerides are converted into fatty acids for
repacking
Phospholipids are transfeered to HDL
VLDL contains fatty acids and cholesterol, is
secreted from liver into the blood, is acted on by
LPL making IDL then LDL
LDL is the major blood transport lipoprotein and
contains apolipoprotein B-100
LDL t1/2 = 1.5 2 days
Biosintesis Cholesterol
Normal
Boderlinehigh
High
Very high
Total
kolesterol
(mg/dl)
LDL
kolesterol
(mg/dl)
HDL
koleserol
(mg/dl)
Trigliserida
(mg/dl)
< 200
200-239
< 130
130-159
< 200
200-400
240
-
160
-
60
-
400-1000
> 1000
1.
HIPERKOLESTEROLEMIA
2.
3.
FAMILIAL
HIPERKOLESTEROLEMIA HETEROZYGOT DAN
HOMOZYGOTE, FAMILIAL DEFECTIVE APO B 100
HETEROZYGOT, POLYGENIC HIPERKOLESTEROLEMIA
CLINICAL PRESENTATION
Asymptomatic
None to chest pain, palpitations, sweating,
anxiety, shortness of breath, loss of
consciousness or difficulty with speech or
movement, abdominal pain, and sudden death
LABORATORY TESTS
Elevations in total cholesterol, LDL, triglycerides,
apolipoprotein B, and C-reactive protein.
Low HDL.
Pengobatan Hiperlipidemia
MENURUNKAN KADAR LIPID DARAH
sesuai dengan target LDL yang harus dicapai
TERGANTUNG DARI ABNORMALITAS LIPID DAN
BERAT RINGAN GGN LIPID
MEMBUTUHKAN WAKTU
Pengobatan Hiperlipidemia
THERAPEUTIC LIFESTYLE CHANGES :
PENGATURAN DIET (pembatasan makanan
berlemak jenuh, peningkatan makanan lemak tak
jenuh)
OLAH RAGA TERATUR (meningkatkan HDL)
MENURUNKAN BERAT BADAN
TERAPY ANTIHIPERLIPIDEMIA
Diberikan apabila therapeutic lifestyle
tidak meberikan hasil
Antihyperlipidemia Mechanism:
Mekanisme antihiperlipidemia
Resin : LDL catabolism,
cholesterol absoption
Niacin: LDL and VLDL synthesis
Menurunkan katabolisme HDL
Clofibrate : VLDL Clearance
Gemfibrosil : VLDL synthesis
Statin : LDL catabolism, inhibit LDL synthesis
Statins menghambat konversi HMG-CoA menjadi
mevalonate,
the rate-limiting step in de novo cholesterol biosynthesis,
melalui penghambatan HMG-CoA reductase
Rosuvastatin merupakan gol statin yang paling poten
Prabucol : LDL clearance
Drug of choice hypercholesterolemia statin --mono terapi paling poten dan cost effective
Bila tidak berespon bisa diberikan kombinasi
terapi namun perlu monitor karena ADR dan
interaksi obat
Hypertryglycerida : niacin, gemfibrozil atau highdose statin (atorvastatin atau simvastatin)
Niacin digunakan secara berhati-hati pada pasien
diabetes ---- memperburuk kontrol glucosa darah
HDL kolesterol rendah :
Modifikasi pola hidup seperti rokok dan exercise
Niacin dan gemfibrosil
Monitoring terapi
1. SERUM LIPID
2. TANDA-TANDA TOKSISITAS OBAT:
FUNGSI HATI (ASAM NIKOTINAT,
CLOFIBRATE, GEMVIBROSIL,
SIMVASTATIN, PRAVASTATIN)
GULA DARAH ( ASAM NIKOTINAT,
GEMFIBROSIL)
KREATININ KINASE (SIMVASTATIN,
PRAVASTATIN, CLOFIBRATE)
SERUM KREATININ DAN UREA
(SIMVASTATIN, PRAVASTATIN)
TUGAS BACA
DOSIS HYPERLIPIDEMIA
DISKUSI DAN
TANYA JAWAB