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OBESITAS

DISLIPIDEMI
SINDROMA METABOLIK
Dr. M a h a t m a SpPD
SMF Penyakit Dalam F.K. UMS
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Digestion and metabolism of dietary fat

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Lipemia is normal , however dyslipidemia is abnormal. We need lipid for
normal body metabolism . There are several kinds of lipids. Lipids are
hydrophobic therefore its must be tranferred in a hydrophilic form as
lipoprotein 11
Bile Acids
Dietary + LIVER
Cholesterol 7 LDL
Fat
2 Apo, B-100
1
Endogenous
Cholesterol

INTESTINES EXTRAHEPATIC
10 TISSUES

3 5

NASCENT HDL

LPL LPL
4 6
HDL3
LDL
REMNANTS VLDL 8 9
CHYLOMICRONS Apo E, B-100
Apo E, B-48 Apo E, C-II, LCAT HTGL
Apo E, C-II, B-48 B-100

Exogenous Endogenous CETP


HDL2
Pathway Pathway
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Diagrammatic representation of lipoprotein metabolism. (Oberman, 1992)
Cholesterol efflux and reverse cholesterol
transport is modulated by two receptors

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Triglyceride-rich lipoproteins:
size, structure and composition

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High-Density Lipoprotein

Apo A-
I
HDL, apo A-I 1 mg/dl (0.026 mmol/l)
and HDL cholesterol
Apo A-II rich
lipoprotein

Cardiovascular
risk

With permission from Professor


-2% -3%
Fruchart
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HDL metabolism and reverse cholesterol transport

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LDL metabolism and reverse cholesterol transport

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INTRODUCTION
OBESITY NOT A NEW FENOMENA
THE VENOUS OF WILLENDORF (25OOO YEARS AGO)

PREVALENCE OF OBESITY INCREASE


Di Amerika 20%(1991)40%(2001) (CARO 2002)
Di koja, Jkt 4,2%(1982) 10,9%(1992)48,6%(2001)(SOEGONDO 2003)
Di Sembiran 19,8%(2002), Sangsit 21,1%(2003), Denpasar
56,1%(2003)(obesitas sentral) (ARYANA 2002;SUASTIKA 2003)

CENTRAL OBESITY HYPERTENSION, DM, DYSLIPIDEMIA,


HYPERINSULINEMIA, SOME RISK FACTORS CHD (METABOLIC
SYNDROME)
DYSMETABOLIC CARDIOVASKULAR SYNDROM (McFarlane 2001)

AUGUST 3-7TH 2006 INTERNATIONAL SYMPOSIUM SHOCK AND CRITICAL CARE


Obesity is caused by imbalance of high
Food intake and or low energy expenditure

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Obesitas
Eropa Asia

IMT > 30 kg/m2 > 25 kg/m2

> 90 > 80 cm
Waist Circumference
> 102 > 90 cm

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PATOGENESIS OBESITAS
Faktor genetik
Parental fatness
7 gen penyebab : - Leptin receptor
- Melanocortin receptor 4
- Alpha-melanocyte stimulating hormone
- Prohormone convertase 1
- Leptin
- Bardert-Biedl
- Dunnigan partial lypodystrophy
Faktor lingkungan : - Nutrisional - Medikasi
- Aktifitas fisik - Sosial ekonomi
- Trauma
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Overweight and Obesity can be treated

Overweight and Obesity widespread, serious


But treatable

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Low Calorie Balance Diets
( LCD )

Awal program : kalori 600 1000 kcal/hari


- Asupan lemak
- Asupan KH
Kalori : 1200 1600 kcal/hari
Protein : 1 g/Kg BB aktual
KH : sisanya

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Very Low Calorie Diets
( LCD )

Formula pabrik
Sering sebabkan gangguan metabolisme
Perlu pengawasan di RS
Utk persiapan operasi

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Berbagai macam obat
Penurun Berat Badan

1. Bekerja di saluran cerna ( penghambat ensim


lipase pankreas ) : orlistat
2. Bekerja menekan pusat nafsu makan di otak :
Lewat jalur serotoninergik : fenfluramine & dexfenfluramine
Lewat jalur noradrenergik : phentermine
lewat jalur serotoninergik & jalur noradrenergik : sibutramine

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Complication
Cancer
Cardiovascular
Diabetes Mellitus
Gallstones
Hiperlipidemia
Obstructive Sleep Apneu
Obesity Hypoventilation Syndrome
Osteoarthritis
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Polycystic Ovarian Syndrome
DISLIPIDEMIA
Kelainan metabolisme lipid, ditandai
dengan peningkatan serta penurunan
fraksi lipid plasma.

TRIAD LIPID
Kol-total/ kol-LDL
Trigliserid (TG)
Kol-HDL.
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Dyslipidemia
Abnormal levels of lipoproteins
(cholesterol, TG. HDL, Lp) or apo-B-
E- A
The metabolic pathways may become
abnormal due to several reasons, whether
primary or secondary :
(HCT, tegretol, niacin, estrogen, glucocorticoids, retinoic
acid, -blockers, diabetes, liver disease, renal failure,
malnutrition etc)
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KLASIFIKASI DISLIPIDEMIA

DISLIPIDEMIA PRIMER
- kelainan pada ensim atau apoprotein
- bersifat genetik
DISLIPIDEMIA SEKUNDER
- akibat penyakit: DM, Peny.ginjal, Tiroid
- akibat obat: diuretika, penyekat beta,
kontrasepsi oral, kortikosteroid.
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Secondary Dyslipidemia
Pathological states Drugs that raise LDL-C and/or
Diabetes lower HDL-C
Hypothyroidism Oral estrogens
Cushings syndrome Progestins
Nephrotic syndrome Anabolic steroids
Chronic renal failure Corticosteroids
Monoclonal gammapathy Retinoids, such as isotretinoin
Obstructive liver disease Sertraline hydrochloride
Human immunodeficiency virus (HIV)
Lifestyle habits protease inhibitors
Obesity Non-selective -adrenergic
Alcohol antagonists
Stress Cyclosporine
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CHD and CV risk factors
Non modifiable risk factors
Age, gender, family history
Modifiable risk factors
Overweight, dyslipidemia
high blood pressure, smoking
physical inactivity, diabetes
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Modifiable risk factors

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Dyslipidemia and Atherosclerosis

Dyslipidemia is characterized by three lipid abnormalities:


Elevated triglycerides
Reduced HDL cholesterol (HDL-C)
Elevated LDL cholesterol (LDL-C) with increased small dense LDL particles

Concomitant endothelial dysfunction leads to atherosclerosis:


Fatty deposits LDL responsible plaques in blood vessels

Responsible for major complications,


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Atherogenicity of small dense LDL

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Liver
SR-B1
9
Lipid + MTP
+ ApoB
Artery
2 Wall
LDLR
8 7 CETP 6
LRP

HDL ABC1
3
LPL Cholesterol
VLDL
Fatty Acids
IDL
HL LPL
1 4 LDL Oxidation
Matrix
HSL Triglycerides Ca++ 5
Inflammation
Smooth
Small muscle
Adipocyte dense cells
LDL

In diabetics cholesterol / LDL level may not sufficient to identify risk


Pathophysiology of diabetic dyslipidemia. (1) FFA due to insulin lack, (2) VLDL is major cause (3)TG metabolized by
LDL, (4) particles by HL, (5) all have access to sub endothelial space, (6) RCT is operative when cholesterol is transferred to HDL
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via ABC-1 (7) transferred further to VLDL through CETP, (8) cleared by receptors LDL-R / LRP (LDL-receptor related protein)
, (9) HDL direct via SR-B1(Semenkovich, 2003)
Mo von Willebrand
P,E-selectins EC
Mo
PSGL-1
VLA-4
VCAM-1
Mac-1, LFA-1
Native LDL ICAM-1
Foam cell

Cytokines
Mo
MCP-1
M-CSF
Proteo- Mo M + HSP-60
glycans
CD40
+ CD40L
MM-LDL LysoPC Oxygen CD36
radicals + T
+
+ SR-A1 CD14
Cell mediated oxidation TLR4 LPS
Oxidized LDL

SMC

Foam cell formation in the intima. LDL can pass into / out intima. If excess it is trapped in the matrix by proteoglycans
binding. At antioxidants lack, lipids and LDL proteins are oxydized by oxidating products from cells in the vessel wall. LDL
proteins are also glycated. Extensive uptake of m-LDL via scavenger receptors (CD36 and SR-A) macrophages are turned into
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foam cells. This process is accelerated by (1) MCSF, (2) LPS via receptor CD14 with toll-like receptor 4 (TLR4), (3) by heat shock
protein (HSP-60) via CD14, (4) by PAF and cytokines released from macrophages in an autocrine loop.(Mehrabian 2003)
Progression to advanced atherosclerotic lesions (3rd step)
Lumen MC
Native Monocytes
LDL
5LO MCP-1 Platelets
LTA4 LTB4
Chemotaxis BLTR
EC
Matrix

MM-LDL
ROS TC Advanced
M-CSF GM-CSF plaque

5LO
Lipid DC IL-1/TNF
Cell ROS
oxidation proliferation
SMC cell proliferation
Cytokine 5LO
oxLDL uptake induction
by SRA GM-CSF NC
5LO
Intima TNF-
Macrophage
IL-1 Procoagulants SMC
adhesion
NF-B, cytokines

Media

5LO (5 Lipoxyoxygenase) and (LTB4) (leukotriene B4) plays very important role in
1st, 2ndand
the10/15/2017 3rdstep of atherogenesis besides LDL oxidation and oxidized LDL
(Mehrabian, 2003)
Biological effect of C-reactive
protein on vascular cells
Adhesion molecules (VCAM-1 and E-selection)
Chemokines (MCP-1)
Expression of eNOS
Release of prostacyclin
Expression of plasminogen activator inhibitor-1
Expression of angiotensin type 1 receptor
LDL uptake by macrophages
Endothelium-independent relaxation of smooth
muscle cells
Generation of ROS
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CRP, inflammation, and endothelial activation

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Inhibits oxidation Inhibits endothelial
of LDLs HDL adhesion molecules

Inhibits Stimulates
tissue factor endothelial NO
production

Enhances reverse
cholesterol transport

Opposes atherothrombosis

Potential mechanisms by which HDLs oppose atherothrombosis.


10/15/2017 (Barter. EMCNA (2004):398)
PENATALAKSANAAN DISLIPIDEMIA

Target : menormalkan fraksi lipid sesuai


faktor risiko PJK yang ada.

Non-farmakologik :
- Life style obesitas
- Terapi nutrisi
- Batasi minuman beralkohol
- Hindari merokok
Farmakologik :
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- Non farmakologik + obat hipolipidemik
Target Lipid

Kolesterol Total
< 200 yg diinginkan
200 239 batas tinggi
240 tinggi
Kolesterol LDL
< 100 optimal
100 129 di atas optimal
130 159 batas tinggi
160 189 tinggi
190 sangat tinggi
Kolesterol HDL
< 40 rendah
> 60 tinggi
Trigliserida
< 150 normal
150 199 batas tinggi
200 499 tinggi
500 sangat tinggi
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Pengaturan makanan utk hiperkolesterolemia

Makanan Asupan yg dianjurkan

Total lemak 25 30% dari total kalori


Lemak saturasi < 7% dari total kalori
Lemak PUFA Sampai 10% dari total kalori
Lemak MUFA Sampai 10% dari total kalori
Karbohidrat 60% total kalori (terutama karbohidrat kompleks)
Serat 10 gr/ kkal perhari
Protein Sekitar 15% dari total kalori
Kolesterol 200 mg/ hari
Total kalori Cukup utk mempertahankan IMT 18,5 25 kg/m2

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Primary Lipid Goal Drugs of Choice

LDL-C (or non-HDL-C) 1st : Statin, Resin, Ezetimibe


per NCEP calculations 2nd : Nicotinic Acid
3rd : Combination

1st : Nicotinic Acid


Secondary Lipid Goals (TG 150-400)
TG < 150 mg/dl Fibrate / fenofibrate
(TG >400)
2nd : Statin, Fish Oil
3rd : Combination

1st : Nicotinic Acid


HDL-C > 40 (men)
2nd : Fibrate, Statin
> 50 (women)
3rd : Combination

The role of nicotinic acid in the treatment of the metabolic syndrome. Nicotinic acid is an effective agent
in the attainment of both primary and secondary goals set by the NCEP. (Meyers. EMCNA 33 (2004):570)
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Where to attack and site of action of some drugs
Cholesterol Absorption in the Intestine

1000 mg

Inhibitors

Resins
Ursodeoxycholate,

Plant stanols NPC1L1


(Ezetimibe)

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Altmann et al. Science 2004; 303: 1201-1204
Cholesterol balance in man

Extrahepatic Dietary
Organs LDL IDL VLDL Cholesterol
300 mg/day
25%
Cholesterol
Synthesis
900 mg/day Biliary
Cholesterol Cholesterol
Synthesis 75%

Transport
via HDL & LDL Chylomicron transport
50% intestinal Faecal sterols
Cholesterol absorbed 50% cholesterol
excreted
Cholesterol lowering drugs
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Statins Ezetimibe Plant stanols Resins
Summary of the major drugs used for the treatment of hyperlipidemias
(Rader 2004)

Drugs Major Mechanism Common side effects


indications
cholesterol
Statins Elevated LDL synthesis, LDL Myalgia, arthralgia, dyspepsia,
hepatic receptor transient transaminase elevation
VLDL production
Bile acid bile excretion LDL Bloating, constipation, elevated
sequestrant Elevated LDL receptors TG
(BAS)
Nicotinic acid Elevated TG, low VLDL hepatic Cutaneous flushing, elevated
(NA) HDL, elevated TG synthesis glucose and UA, and LFT
Fibric acid Elevated TG, and LPL, VLDL Dyspepsia, myalgia, gallstones,
derivatives remnants synthesis OT/PT
Severely elevated VLDL and
Fish oil TG chylomicron Dyspepsia, fish odor, diarrhoea
production
Specific
Cholesterol Intestinal cholesterol
absorption Elevated LDL absorbtion Elevated transaminase
inhibitors
(SCAI)
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The effects of several antidyslipidemic drugs are seen
below: Lipid lowering drugs

Lipoprotein Nicotinic Bile-acid HMG-CoA Fibrates


acid sequestrants Reductase (gemfibrozil,
Inhibitors fenofibrate)
( statin )
Chylomicrons ? ? ?
VLDL or ?
IDL or ?
LDL or
HDL or or or

Larosa 1995

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Tabel 7. Obat Hipolipidemik
Obat Dosis

Gol. Resin Pengikat Asam Empedu


- Kolestiramin 4 24 gr/hari
- Kolestipol 5 30 gr/hari
Gol. Asam Nikotinat
- Asam Nikotinat 100 mg/ 2 x sehari ditingkatkan
sampai 1,5 3 gr/hari
- Acipimox 250 mg 2 x sehari
- Niacin ER 1000 2000 mg 1 x sehari
Gol. Statin
- Fluvastatin 40 80 mg malam hari
- Lovastatin 5 40 mg malam hari
- Pravastatin 5 40 mg malam hari
- Simvastatin 5 40 mg malam hari
- Atorvastatin 10 80 mg malam hari
- Rosuvastatin 10 40 mg malam hari

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Lanjutan

Obat Dosis

Gol. Asam fibrat


Bezafibrat 200 mg 3 x sehari atau
400 mg sekali sehari (retard)
Fenofibrat 100 mg 3 x sehari atau
300 mg sekali sehari
Gemfibrozil 600 mg 2 x sehari atau
900 mg sekali sehari
Golongan lain
Probukol 500 mg 2 x sehari

Penghambat absorbsi lemak


Ezetimibe 10 mg sekali sehari

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Sequestran asam empedu (resin)
Efektif kol-LDL
Mengikat as.empedu di usus ---- ekskresi garam
empedu feces .
Memotong siklus enterohepatik
Asam nikotinat (niacin)
Hambat mobilisasi as.lemak bebas jar. perifer ke
hepar.
Sintesis TG & VLDL di hepar
Hambat konversi VLDL menjadi IDL
Meningkatkan GLUKOSA & asam urat plasma
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NICOTINIC PERIPHERAL
ADIPOCYTE TISSUES
ACID
* Cholesterol
TG
HDL
HSL

FFA Acyl Acetyl


CoA CoA

DGAT2
TG DG
HDL
Cholesterol
VLDL
PL HEPATOCYTE
Cholesterol
B100

Mechanisms of action of NA Nicotinic acid inhibits hepatic TG synthesis at the level of FA synthesis and
esterification of DG. NA also blocks apoAI-containing HDL holoparticle uptake at the liver without altering
transport of cholesterol from HDL to the liver by SRB1. Finally, NA acutely inhibits adipocyte lipolysis, but the
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Meyers EMCNA 33 (2004):561)
Liver
Mobilization
(-) (-) TG synthesis

Peripheral
Tissue FFA

(-)
Niacin
assembly of (-)
ApoB containing TG-rich VLDL
lipoproteins (-)
(-)
ApoB degradation Small dense LDL

HDL-catabolism (+) (+) reverse cholesterol


receptor HDL ApoAI transport
uptake/removal

Niacin (nicotinic acid) inhibits the mobilization of free fatty acids (FFA) from peripheral tissues, which
reduces the (TG) and decreases (VLDL), which lowers (LDL). Niacin decreases the activity (HDL)-
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catabolism receptor, reducing uptake and degradation of HDL, stimulates RCT. Niacin lowers (apoB)
Penghambat HMG-CoA reduktase

Menurunkan produksi kolesterol hepar


Mengaktifasi Sterol Regulatory Binding
Protein (SREBP)--- ekspresi reseptor
LDL .
Katabolisme LDL meningkat
Uptake VLDL & IDL oleh reseptor LDL , TG plasma .
Kombinasi dgn NIACIN atau FIBRAT-----
miopati atau gangguan fungsi hepar.
Pd hiperkolesterolemia berat, kombinasi dg RESIN.
Efek pleiotropik---- cegah aterosklerosis.

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Penghambat absorbsi kolesterol
(ezetimibe)

Hambat kol. makanan & kol. Cairan empedu di


usus halus. (NPC1L1).
Timbunan kol. di hepar .
Klirens kol. plasma .
Utk kol-total, kol-LDL dan Apo-B pd
hiperkolesterolemia primer.
Efektif sbg mono terapi maupun kombinasi dg
statin.

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Ezetimibe
glucuronide

Ezetimibe

Bile duct

Portal
Ezetimibe
vein
Ezetimibe
glucuronide Inhibition
of
cholesterol
absorption

Ezetimibe Ezetimibe
glucuronide
Enterohepatic recirculation of ezetimibe and its glucuronide. On first pass, ezetimibe inhibits cholesterol absorption in the
brush border of the small intestinal enterocytes. The drug is then partially transformed by the enterocytes into its main
metabolite, ezetimibe glucuronide. Further metabolism takes place in the liver and the active glucuronide metabolite is
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excreted back in the intestine through the bile duct. Inhibition of cholesterol absorption is prolonged and the glucuronide
is reabsorbed and recirculated through the bile duct. (Simord, Can J Clin Pharmacol 2003, etc)
Fibrat (derivat asam fibrat)
- Sangat tepat untuk hipertrigliseridemia.
- Dapat untuk hiperlipidemia kombinasi
- Dapat dikombinasi dengan RESIN & NIACIN, kom
binasi dengan statin dapat timbul miopati, Gemfi-
brosil jangan dikombinasi dengan statin.
- Bekerja pada peroxisome proliferator-activated re
ceptor- (ppar-)
- Jarang: transaminase hepar naik, batu empedu,
kreatin kinase otot naik, libido turun.
- Efek potensiasi dg Obat Hipoglikemik Oral dan an-
ti-koagulan oral.
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FIBRATES
gemfibrozil, fenofibrates

Glitazones

Eicosanoids

PPAR
PPAR

- Activated PPAR
Nucleus - Retinoid R
PPAR

AGGTCA N AGGTCA

Target Genes Regulating 5


PPRE Lipoprotein Metabolism
(Peroxysome Proliferator Responsive Elements)

Mechanism
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of action of fibrates on lipoprotein metabolism.
Peroxisome Proliferator-Activated Receptor- a transcription factor
Obat baru :
- NIACIN extended release (NIASPAN)
- Fix kombinasi NIACIN ER + LOVASTATIN
(advicor)

Obat masa depan:


- Penghambat cholesteryl ester transfer protein
(CETP) -------> HDL
- Penghambat microsomal transfer protein (MTP)
- Penghambat intestinal bile-acid transporter.
(IBAT)
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Summary of the major drugs used for the treatment of hyperlipidemias
(Rader 2004)

Drugs Major Starting dose Maximal Mechanism Common


indications dose side effects
Statins
Lovastatin 20 mg daily 80 mg day cholesterol Myalgia,
Pravastatin 40 mg qhs 80 mg qhs synthesis, LDL arthralgia,
Simvastatin Elevated LDL 20 mg qhs 80 mg qhs hepatic receptor dyspepsia,
Fluvastatin 20 mg qhs 80 mg qhs VLDL production transient
Atorvastatin 10 msg qhs 80 mg qhs transaminase
Rosuvastatin 10 mg qhs 40 mg qhs elevation

Bile acid
sequestrants 32 g daily Bloating,
Cholestyramine Elevated LDL 4 g daily 40 g daily bile excretion constipation,
Colestipol 5 g daily 4375 mg LDL receptors elevated TG
Colesevelam 3750 mg daily daily

Cholesterol
absorbtion Elevated LDL 10 mg daily 10 mg daily Intestinal Elevated
inhibitors cholesterol transaminase
Ezetimibe absorbtion

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New antilipid drugs
Treatment Site of Dosage Change from base line (%)
action
LDLc HDLc TG
Monotherapy
Avasimibe ACAT-I 50-500 mg NS NS -23
JTT-705 CETP-I 300-900 mg -77 +34.5 NS
Colesevelan Bile acid sequestrant 3.75 gram -19.1 +11,2 NS
Ezetimibe Specific Cholesterol 10 mg -17.7 +1 -17
Absorption Inhibitor
Rosuvastatin HMG-CoA reductase 10-40 mg -63 +14 -23
inhibitor
Pitavastatin HMG-CoA reductase 2 mg -38 +4.2 -23
inhibitor
Combination therapy
ER niacin 500mg/10mg- -47 +30 -42
Lovastatin 2000mg / 40mg
Colesevelan - 2.5mg/40mg -34 NS NS
Lovastatin

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(Law et al. BMJ 2003 ; 326 : 1423-29)
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Pathogenesis ? Even suggested pathogenesis is useful for prevention program.
a. Genetic abnormality b. Fetal malnutrition c.Visceral obesity

Food intake Genetic Physic


excess background inacting

Adipo Genesis Overweight


Obesity

Insulin Resistance

Pancreatic Hyperinsulinemia
-cell stress &
damage
*
Inadequate Compensatory
Insulin Response Hyperinsulinemia

Type 2 Diabetes Insulin Resistance


Syndrome

CVD
Retinopathy Hypertension
Nephropathy Stroke
Neuropathy PCOS
NAFLD
*ACE position statement (2003)

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Differentiation between the Insulin Resistance Syndrome and type 2 diabetes.
Modified from ACE (2003) & Tenenbaum (2003) (Djokomoeljanto, 2004) DM-BR- 2004
Visceral Obesity Risk Factors CHD

Hyper- Dyslipidemia
tension

Type 2
Diabetes

Anti lipid lowering drug

Treating the cause by diet, Treating the complications ? Optimal management


exercise, pharmacology of CHD risk

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Presented by Prof. John MF Adam
FFA Lipid
FFA
Leptin
Adiponectin

Adipose Visfatin
Tissue Resistin
Adipsin (ASP)
Angiotensinogen/AT-II
Cytokines
(TNF-, IL-6)
Prostaglandin NO PAI-1

Adipokines Secreted by Adipose Tissue


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DM-BR- 2004
PROTEIN YANG DISEKRESI ADIPOSIT

1. ESTROGEN 16. VISFATIN 31. RBP


2. LEPTIN 17. HSL 32. APO-E
3. AGOUTI RELATED PROTEIN 18. LIPOTRANSIN 33. ICAL
4. TNF 19. PERILIPINS 34. LPL
5. IL1B 20. FFAs 35. CETP
6. IL-6 21. TGF- 36. PLTP
7. ANGITENSINOGEN 22. VEGF 37. NO
8. ASP 23. IGF-1 38. PC-1
9. ADIPSIN 24. PGE2 39. AQUAPORINS
10. FACTORS B,C3 25. PGI1 40. FIAF
11. ADHESIVE PROTEIN 26. GLUCOCORTICOID 41. LACTATE
12. PAI-1 27. 11HSD 42. MONOBUTYRIN
13. TF 28. AROMATASE 43. GALACTIN-12
14. RESISTIN 29. METALLOTHIONIEN 44. ESM-1
15. ADIPONECTIN 30. MIF 45. APELIN

(TJOKROPRAWIRO 2003)
AUGUST 3-7TH 2006 INTERNATIONAL SYMPOSIUM SHOCK AND CRITICAL CARE
Macrophage
ABCA1 Chol
FFA Liver ABCA1
FFA
pre HDL (nascent HDL)
Adipocytes CE
Kidney
Insulin VLDL CETP HDL
Resistance
(T2DM) TG
VLDL TG Apo AI
CE CETP
Insulin TG
small
LDL dense
(lipoprotein or
LDL
or hepatic lipase)

A simplified model that relates insulin resistance ( includes type 2 diabetes mellitus)
to high TG, low HDL-C, small-dense LDL (Assmann. EMCNA (2004):389)
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Insulin resistance Glucose
Insulin

Translocation
Insulin
receptor
X

X Synthesis GLUT 4
PPAR +RXR mRNA

PPRE transcription
promoter Coding reg
Muscle
Cells
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Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2nd Ed.
S U M M A R Y
Definisi Dx Drug Komplikasi
Cancer
Akumulasi Cardiovascular
jaringan lemak Diabetes Mellitus
berlebihan, baik Orlistat Gallstones
IMT
Obesity besar maupun Sibutramine Hiperlipidemia
WC Obstructive Sleep Apneu
jumlahnya
Obesity Hypoventilation Syndrome
Osteoarthritis
Polycystic Ovarian Syndrome

Kelainan TG Statin
Dislipidemi metabolisme CH Niacin
Ezetimibe
Aterosklerosis
lipid LDL
HDL Nicoitinic C H D
WC
Dislipidemia
Kumpulan Aterosklerosis
Ht
gejala yang
Metabolic DM Metformin C H D
disebabkan oleh
Syndrome TG Glitazone
karena obesitas
CH
Hipertensi
sentral Diabetes Mellitus
LDL
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HDL
SUMMARY
The relation between dyslipidemia cardiovascular
disease is confirmed. Primary dyslipidemia should be
treated concomitantly
Dyslipidemia fit also to the current concept of athero-
sclerosis : lipid and inflammatory process
Any lipid abnormality (HDL, TG, etc) should also be
corrected.
Statin should be the backbone of cardiovascular
treatment due to its cholesterol lowering and its
pleiotropic potencies
Aggressive cholesterol lowering is beneficial
In combined dyslipidemia, treatment combination is
sometimes needed
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