HIPERLIPIDEMIA DAN

HIPERLIPOPROTEINEMIA
Dra. Fita Rahmawati, Sp.FRS, Apt

Objectives

Memahami patofisiologi hiperlipidemia

Identifikasi klasifikasi hiperlipidemia
Memahami tujuan terapi dari hiperlipidemia
Memahami tata laksana terapi hiperlipidemia
Non farmakologi - Lifestyle modification
Farmakologi
Monitoring terapi hiperlipidemia

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 %

 Lipid nutrition required for health

Cholesterol is used to make prostaglandins,
leukotrienes, glucocorticoids, mineralocorticoids,
androgens, estrogens and bile acids

LIPID and LIPOPROTEIN

LIPID

Triglycerides
Cholesterol
Phosospholipids/
Lechitin

LIPOPROTEIN

chylomicrons

VLDL, IDL, LDL, HDL

[Lp(a)], -VLDL

STRUKTUR LIPOPROTEIN

PATOPHYSIOLOGY

ATERIOSKLEROSIS & ATEROSKLEROSIS

ATERIOSKLEROSIS MERUPAKAN PENYAKIT
YANG DITANDAI DENGAN PENEBALAN DAN
HILANGNYA ELASTISITAS DINDING
ARTERI.
BENTUK PALING UMUM :
ATEROSKLEROSIS, ATEROM PADA INTI
ARTERI BERISI KOLESTEROL, ZAT LIPOID ,
LIPOFAG

MENGENAI PEMBULUH DARAH ARTERI

BESAR DAN SEDANG : PEMBULUH
CEREBRAL, KORONER, RENAL,
VERTEBRAL DAN AORTA

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

Efek obat pada serum lipid

Gol. obat

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

 LDL receptor on cells are involved in delivery lipids

LDL receptors have a large extracellular apolipoprotein B100 binding domain
Liver removes 75 % of blood LDL
Statin and fasting increase liver LDL receptor expression
LDL binds to the receptors and deliver lipid to cells through
endocytosis
LDL is taken up into endosomes/lysosomes,
LDL receptors recycle to the surface, cholesterol esters
(linoleate) are liberated, cleaved by lysosomal acid lipase
and taken into the Golgi apparatus, cholesterol can be
esterified (oleat and palmitate) by ACAT (acyl CoA
cholesterol acyltranferase) for storage in the cell.
Free cholesterol can be used in the cell membrane

The Exogenous and Endogenous pathways for

triglyceride and cholesterol transport

Biosintesis Cholesterol

Klasifikasi nilai kolesterol dan trigliserida

Klasifikasi

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

JENIS-JENIS HIPERLIPOPROTEINEMIA GENETIK

1.

HIPERKOLESTEROLEMIA

2.

HIPERTRIGLISERIDA :FAMILIAL HIPERTRIGLISERIDA;

3.

HIPERTRIGLISERIDA & HIPERKOLESTEROLEMIA:

FAMILIAL
HIPERKOLESTEROLEMIA HETEROZYGOT DAN
HOMOZYGOTE, FAMILIAL DEFECTIVE APO B 100
HETEROZYGOT, POLYGENIC HIPERKOLESTEROLEMIA

FAMILIAL LPL DEFICIENCY; FAMILIAL APO CII

KOMBINASI HIPERLIPIDEMIA;
DYSBETALIPOPROTEINEMIA

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:

Decrease synthesis of VLDL & LDL,

Agents that enhance VLDL clearance,
Agents that enhance LDL catabolism,
Agents that decrease cholesterol absorption,
Agents that elevate HDL, or
some combination of these characteristics

Jenis obat hiperlipidemia

Statin atau HMG Co-ARI
(hydroxymethylglutaryl coenzyme-A
reductase inhibitor) : Simvastatin,
Pravastatin
BAR (Bile acid resins) : Cholestyramin ,
Colestipol
Fibric acids : Clofibrate, Gemfibrozil
Fish oil
Probucol
Nicotinic acid (niacin)

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

Fish oil : synthesis of VLDL - triglycrida

 HDL dapat ditingkatkan melalui

Olah raga, pembatasan kosumsi alkohol <
2x/hari, penghentian merokok, penurunan
berat badan
Oral kontrasepsi, phenitoin dan terbutalin
Niacin dan gemfibrosil
HDL dapat diturunkan melalui:
Merokok, obesitas, sedentary life style,
bloker menurunkan HDL

 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