farmakoterapi i hiperlipidemia 2013

8/18/2019 Farmakoterapi I Hiperlipidemia 2013

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HIPERLIPIDEMIA DAN

HIPERLIPOPROTEINEMIA

Dra. Fita Rahmawati, Sp.FRS, Apt


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Objectives

• Memahami patofisiologi hiperlipidemia

• Identifikasi klasifikasi hiperlipidemia

• Memahami tujuan terapi dari hiperlipidemia

• Memahami tata laksana terapi hiperlipidemiaNon farmakologi - Lifestyle modification

Farmakologi

• Monitoring terapi hiperlipidemia


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DEFINISI

HIPERLIPIDEMIA :PENINGKATAN KADAR LIPID PLASMA

DARAH KOLESTEROL DAN ATAU TRIGLISERIDA

HIPERLIPOPROTEINEMIA : PENINGKATAN KADARMAKROMOLEKUL LIPOPROTEIN YANG MENGANDUNGLIPID DALAM PLASMA

PENTING --- HYPERKOLESTEROL, HDL RENDAH DANTERUTAMA PENINGKATAN LDL BERHUBUNGAN DENGANPENYAKIT JANTUNG KORONER (PJK) DANCEREBROVASCULAR MORBIDITY DAN MORTALITY

PENURUNAN KOLESTEROL MENURUNKAN PENYAKITKORONER 20 %


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• Lipid nutrition –required for health

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


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LIPID– Triglycerides– Cholesterol

– Phosospholipids/Lechitin

LIPOPROTEINchylomicrons

VLDL, IDL, LDL, HDL

[Lp(a)], ß-VLDL

LIPID and LIPOPROTEIN


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STRUKTUR LIPOPROTEIN


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PATOPHYSIOLOGY


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ATERIOSKLEROSIS ATEROSKLEROSIS

ATERIOSKLEROSIS MERUPAKAN PENYAKIT YANG DITANDAI DENGAN PENEBALAN DANHILANGNYA ELASTISITAS DINDINGARTERI.

BENTUK PALING UMUM :ATEROSKLEROSIS, ATEROM PADA INTI

ARTERI BERISI KOLESTEROL, ZAT LIPOID ,LIPOFAG

MENGENAI PEMBULUH DARAH ARTERIBESAR DAN SEDANG : PEMBULUH

CEREBRAL, KORONER, RENAL,VERTEBRAL DAN AORTA


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PENYEBAB HIPERLIPIDEMIA

1. PRIMER (MONOGENIK) KETURUNAN/GENETIK

The primary defect in familial hypercholesterolemia is theinability to bind LDL to the LDL receptor (LDL-R)

2. SEKUNDER/POLIGENIK/MULTIFAKTORIALPENYAKIT LAIN : DM, HIPERTIROIDDIET : ALKOHOL , MEROKOK

OBAT-OBATAN : TIAZID, ESTROGEN


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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 0 – 9 % 0 – 16 % 0 – 17 %

Estrogen 5 % 40 – 60 %

Cyklospori 15 – 20 % Tetap Tetap

Captopril Tetap Tetap

Methyldopa 5 – 10 % 0 – 25 % Tetap


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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


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Lipid metabolisme


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• UPTAKE

Fats from the diet are cleaved by gastric lipaseSolibilized in the gut by bile acidsThe emulsified complexes enter the gut mucosaand are packaged into chylomicrons

They are transported in the lymph then the bloodChylomicron are substrates for lipoprotein lipase(LPL, liberating triflycerides) in endothelial cells,fat cells, muscle and the liver, leaving chylomicronremnants

Fats are released that are taken up by cells


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• REPACKINGThe liver libetrates lipids from chylomicron

remnants and repackages then into lipoproteins.Triglycerides are converted into fatty acids forrepackingPhospholipids are transfeered to HDL

VLDL contains fatty acids and cholesterol, issecreted from liver into the blood, is acted on byLPL making IDL then LDLLDL is the major blood transport lipoprotein andcontains apolipoprotein B-100

LDL t1/2 = 1.5 – 2 days


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• LDL receptor on cells are involved in delivery lipids

LDL receptors have a large extracellular apolipoprotein B-100 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 throughendocytosis

• LDL is taken up into endosomes/lysosomes,

LDL receptors recycle to the surface, cholesterol esters(linoleate) are liberated, cleaved by lysosomal acid lipaseand taken into the Golgi apparatus, cholesterol can be

esterified (oleat and palmitate) by ACAT (acyl CoAcholesterol acyltranferase) for storage in the cell.

Free cholesterol can be used in the cell membrane


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The Exogenous and Endogenous pathways fortriglyceride and cholesterol transport


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Biosintesis Cholesterol


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Klasifikasi nilai kolesterol dan trigliserida

Klasifikasi Totalkolesterol(mg/dl)

LDLkolesterol(mg/dl)

HDLkoleserol(mg/dl)

Trigliserida(mg/dl)

NormalBoderline-high

High

Very high

< 200200-239

240

-

< 130130-159

160

-

--

60

-

< 200200-400

400-1000

> 1000


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CLINICAL PRESENTATION

• Asymptomatic• None to chest pain, palpitations, sweating,

anxiety, shortness of breath, loss ofconsciousness or difficulty with speech ormovement, abdominal pain, and sudden death

• LABORATORY TESTSElevations in total cholesterol, LDL, triglycerides,apolipoprotein B, and C-reactive protein.

Low HDL.


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Pengobatan Hiperlipidemia

• MENURUNKAN KADAR LIPID DARAH– sesuai dengan target LDL yang harus dicapai

• TERGANTUNG DARI ABNORMALITAS LIPID DANBERAT RINGAN GGN LIPID

• MEMBUTUHKAN WAKTU


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Pengobatan Hiperlipidemia

• THERAPEUTIC LIFESTYLE CHANGES :

PENGATURAN DIET (pembatasan makananberlemak jenuh, peningkatan makanan lemak tak

jenuh)

OLAH RAGA TERATUR (meningkatkan HDL)

MENURUNKAN BERAT BADAN

• TERAPY ANTIHIPERLIPIDEMIA

Diberikan apabila therapeutic lifestyle

tidak meberikan hasil


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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


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Jenis obat hiperlipidemia

• Statin atau HMG Co-ARI(hydroxymethylglutaryl coenzyme-Areductase inhibitor) : Simvastatin,Pravastatin

• BAR (Bile acid resins) : Cholestyramin ,Colestipol• Fibric acids : Clofibrate, Gemfibrozil• Fish oil

• Probucol• Nicotinic acid (niacin)


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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 menjadimevalonate,

the rate-limiting step in de novo cholesterol biosynthesis,melalui penghambatan HMG-CoA reductaseRosuvastatin merupakan gol statin yang paling poten

• Prabucol : LDL clearance• Fish oil : synthesis of VLDL - triglycrida


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• HDL dapat ditingkatkan melalui

Olah raga, pembatasan kosumsi alkohol <2x/hari, penghentian merokok, penurunanberat badanOral kontrasepsi, phenitoin dan terbutalin

Niacin dan gemfibrosil

• HDL dapat diturunkan melalui:Merokok, obesitas, sedentary life style,β bloker menurunkan HDL


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• Drug of choice hypercholesterolemia statin ---mono terapi paling poten dan cost effective

• Bila tidak berespon bisa diberikan kombinasiterapi namun perlu monitor karena ADR daninteraksi obat

• Hypertryglycerida : niacin, gemfibrozil atau high-dose statin (atorvastatin atau simvastatin)

Niacin digunakan secara berhati-hati pada pasiendiabetes ---- memperburuk kontrol glucosa darah

• HDL kolesterol rendah :Modifikasi pola hidup seperti rokok dan exercise

Niacin dan gemfibrosil


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Monitoring terapi

1. SERUM LIPID2. 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)


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TUGAS BACA

• DOSIS HYPERLIPIDEMIA


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DISKUSI DAN

TANYA JAWAB

farmakoterapi i hiperlipidemia 2013

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