ANTI HYPERLIPIDEMIC

Hernita Taurustya
Kardiovascular Module
FKIK UNIB 2020
 Classification
Class Density Electropho- Size
retic mobility (nm)
Chylomicrons < 0.94 origin 70-120
Very low density LP (VLDL) < 1.006 pre- 30-70
Intermediate-density LP (IDL) = 1.006-1.019  23-30
Low-density LP (LDL) = 1.019-1.063  18-23
High density LP (HDL) = 1.063-1.215  5-12
* Lipoprotein (a) pre- 23-26
 Composition
Lipo- Chyclomi- VLDL (%) LDL (%) HDL (%)
protein crons (%)
Triglyceride 80-90 45-65 4-8 2-7
Cholesteryl 2-4 16-22 45-50 15-20
esters
Free cholesterol 1-3 4-8 6-8 3-5
Phospholipid 3-6 15-20 18-24 26-32
Protein 1-2 6-10 18-22 45-55
Apolipoprotein B-48, AI, AIV, B-100, CI, B-100 AI, AII, CI,
species CI, CII, CIII, E CII, CIII, E CII, CIII, D, E
 Treatment goals
Strategy Target Concen-
tration of LDL
Primary prevention
Men < 35 years and premenopaused women < 190 mg/dl
Men > 35 years and women > 45 years < 160 mg/dl
with < 2 other CV risk factor
Adults with > 2 other CV risk factor < 130 mg/dl
Adults with diabetes mellitus or a strongly < 100 mg/dl
family history of early CV disease
Secondary prevention < 100 mg/dl
 Treatment goals
Cholesterol : - vitamin D
- steroid hormones
- bile acid
Therapy : 1. Secondary cause (hypothyroidism, DM)
2. Dietary modification 3-6 months
3. Hypolipidemic agents
Choice : Hypercholesterolemia : Bile acid sequestrants-
niacin-
statins-gemfibrozil
Hypertriglyceridemia : Gemfibrozil-niacin-statins
Treatment goals
Hypolipidemic agents :
1. Fibric acids
2. Bile acid sequestrants
3. HMG-CoA reductase inhibitors (statins)
4. Probucol
5. Nicotinic acid
FIBRIC ACIDS

 M.A: - ligand for peroxisomal proliferator

activated receptor (PPAR)
- LP lipase   VLDL catabolism 
VLDL , IDL  , LDL  (in primary
hypertriglyceridemia, type IV) or  (in
hypercholesterolemia, type II), HDL 
Kinetics
Oral
Highly bound to protein (90-95%)
Enterohepatic circulation
Elimination : kidney
* Fenofibrate : prodrug
* Gemfibrozil : homolog of clofibrate
 22% reduction in death from CHD or non fatal MCI
 1st line treatment of hypertriglyceridemia
2nd line treatment other hyperlipidemias
S.E.

 GI tract
 Rash, alopecia
 Myositis (bezafibrate), CPK , SGOT 
 Lithogenicity index 
Indication
 Hypertriglyceridemia
FA : - TG  (25-60%)
- Cholesterol  (5-25%)
- HDL  (10-20%)
- LDL  (10-20%) or  (5-20%)

 Hypercholesterolemia (type II b) DM, nephrotic

syndrome
 Dysbetalipoproteinemia (type III)
Contraindication

 Pregnancy, lactation
 Liver, kidney diseases
 Anticoagulants
 BILE ACID SEQUESTRANTS (RESINS)
Cholestyramine, colestipol
M.A Liver
Cholesterol pool
cholesterol-7 hydroxylase
Bile acids
Resins (cholic, chenodeoxycholic acid)
secreted by liver
Bile
Reabsorbed (Pl, bile acids, unesterified cholesterol)
by ileum 
intestine

faecal sterol
 Results
Cholesterol content 

HMG-CoA reductase inhibition 

Cholesterol synthesis 
LDL receptors 

Net results :
- LDL catabolism  in liver  plasma cholesterol 
- Compensatory increases in cholesterol and TG
synthesis
Results

Lipid Research Clinic Primary Prevention

Trial (1984) cholestyramine monotherapy : 12%
reduction of LDL and 19% reduction in CAD.
However, total mortality was unchanged.
S.E.
 Constipation, flatulence, nausea, vomiting, poor
palatability
 SGOT , AP , hyperchloremic acidosis,
hypoprothrombinemia
 Impair absorption of drugs: digoxin,
furosemide, gemfibrozil, niacin, thiazides,
warfarin, NSAIDs, aspirin, vitamins A,D,E,K
etc. give other drugs 1 h before or 4 hs after
resins. Resins administration with meals.
Indication

 Hyperlipoproteinemia (type II)

  Homozygous familial hypercholesterolemia
  Hypertriglyceridemia
 Probably safe for pregnant and lactating women,
children (but pay attention to fat sol. vitamins
availability)
 Reduce pruritus in partial biliary obstruction.
 STATINS (HMG-CoA reductase inhibitors
M.A : Acetyl - CoA

HMG - CoA
 HMG - CoA reductase
Mevalonate

Farnesyl pyrophosphate Farnesy-

 lated
Squalene proteins

Ubiquinone Cholesterol
Dolichol
 STATINS (HMG-CoA reductase inhibitors
Statins (lovastatin, simvastatin, pravastatin,
fluvastatin, atorvastatin, cerivastatin)
 Competitive inhibitors of HMG-CoA reductase
 cholesterol synthesis  (modest)
 LDL receptors 
45 study (Scandinavian Simvastatin Survival
Study Group, 1994)
 Total cholesterol  25%
 LDL  35%
 TG  10%
 HDL  8%

42% reduction in mortality from CHD

30% reduction in mortality from all causes
Kinetics

 Oral : absorption varies, 12% (atorvastatin), > 90%

(fluvastatin)
 All except cerivastatin undergo extensive first pass
metab.  target : liver
 Lovastatin & simvastatin : prodrug
Indications
 Hypercholesterolemia (heterozygous familial
hypercholesterolemia / type II
hyperlipoproteine-mia and polygenic forms)
S.E.
 Liver function , SGPT  > 3x  stop therapy
Liver function monitoring 4-6 weeks (11/2 years)
 Myositis, rhabdomyolisis  CPK  >10 x normal
X combination with cyclosporine, gemfibrozil, niacin,
erythromycin, imidazole antifungals
 Skin rash, GI complaints
Contraindication

 Premenopausal women, nursing

M.A. :
NIACIN (nicotinic acid)
 In adipose tissue:
hormone sensitive hepatic TG synthesis ↓
TG
lipase transport FFA to liver

niacin
 In liver: inhibits FFA synthesis & esterification  TG
synthesis ↓
 VLDL ↓  LDL-C ↓
 Enhances LPL activity  chylomicrons & VLDL
triglyceride clearance ↑
 Increases HDL
Kinetics

 Oral : rapid & complete

 First-pass metabolism
 t 1/2 : 45 min.
 Distribution : all tissues
 Excretion : kidney
Indications :
 1st line agent for hypertriglyceridemia and
hypercholesterolemia
 Type III, IV, & V hyperlipoproteinemia
S.E.
 Flushing, pruritus, dryness, hyperpig-
mentation
 Liver dysfunction : AP , SGPT , SGOT 
 GI complaints
 Atrial fibrillation, ventricular ectopy
 Glucose intolerance, uric acid 
Contraindications :

 Peptic ulcer
PROBUCOL

 M.A. : LDL  (not TG), antioxidant

HDL  
 Indication : type IIA hypercholesterolemia
 Side effects : - GI complaints
- Odorous perspiration
- Blood abnormality
- Liver dysfunction
 Dietary and biliary cholesterol
absorption inhibitor
Ezetimibe (azetidione-based cholesterol
absorption inhibitor)

M.A. : block intertinal absorption of chol.

 total cholesterol ↓ and LDL-C ↓

Kinetics : glucorunidation in intestine 

active metabolic  bile
(enterohepatic circulation)
t ½ : 22 h
Studies :
 10 mg daily  LDL-C ↓ 19%
 20 mg simvastatin + 10 mg ezetimibe  LDL-C ↓ 52%
~ 80 mg simvastatin
margin of safety ↑

Indications :
 Primary hypercholesterolemia
 Homozygous familial hypercholesterolemia
Others

 Neomycin, activated charcoal, psyllium

hydrophilic mucilloid, -sitosterol, D- thyroxin
Ezetimibe

MA :
 Inhibits absorption of phytosterols and
cholesterol
 Effective even in the absence of diaetary
cholesterol
Kinetics :
- Well absorbed, conjugated in intestine to active
glucuronide
- Undergoes enterohepatic circulation
- T ½ : 22 h, 80% excreted in faeces
- Plasma conc  + fibrates
 + cholestyramine
- No significant interaction with warfarin, digoxin
Indication :
- 10 mg single dose
LDL in primary cholesterolemia  18%
HDL slightly 
- Synergistic + statin ( 25%)
S.E. :
- Not a substrate for cytochrome P450
- Reversibly impaired hepatic function
- Liver function test every 2-4 mo.
OBAT PADA PJK

HERNITA TAURUSTYA
KARDIOVASCULR MODULE
FKIK UNIB 2020
OKSIGEN
 Pemberian suplemen O2 diberikan pada pasien
dengan desaturasi O2 (SaO2 <90%)
 Suplemen O2 mungkin membatasi injury
miokard atau bahkan mengurangi elevasi ST
 Pemberian suplemen O2 rutin > 6 jam pertama
pd kasus tanpa komplikasi, belum terdapat
landasan ilmiah yang kuat.

ACC/AHA Guideline of STEMI 2004

 Anti Platelet
ASPIRIN
CLOPIDOGREL
Gp IIb / IIIa inhibitor
 ASPIRIN
 MANFAAT : menurunkan angka reinfark 50%
dalam 30hari ; 20% penurunan mortalitas dlm 2
tahun
 Dosis 81-325 mg P.O.
 Trials: ISIS (88), Antiplatelet Trialist Group (94),
HART (90)

Aspirin kunyah segera diberikan meskipun

belum ada hasil EKG
(non coated/slow released)
Adenosine Diphosphate Inhibitors

 ADP disekresi oleh platelet (aktivasi dan

agregasi platelet)
 P2T cell surface receptors
 Ticlodipine
 Clopidogrel
 Efek samping : Neutropenia, trombositopenia
 Synergistic Mode of Action with
Clopidogrel and ASA1

CLOPIDOGREL C

ADP

ADP

GPllb/llla Collagen thrombin

Activation
(Fibrinogen receptor) 2
TXA

ASA
ASA COX

TXA2

COX (cyclo-oxygenase)
ADP (adenosine diphosphate)
TXA2 (thromboxane A2)

1. Schafer AI. Am J Med 1996; 101: 199–209.

Clopidogrel
 Gol Thienopyridine yg memblok P2Y reseptor ADP
 Menghambat aktivasi platelet

•Digunakan pada pasien UA/NSTEMI :

Diberikan pada semua pasien
Bukan kandidat CABG
Pasien yg direncanakan kateterisasi dlm
24-36 jam stlh masuk
Glycoprotein IIb/IIIa Inhibitors

 50,000 receptors per platelet

 Aggregation final common pathway
 “Passivation”; stops deposition
 Abciximab (Reopro); tirofiban (Aggrastat);
eptifibatide (Integrilin) and lamifiban (Canada)
 Pre-PCI/ Procedural Coronary Intervention
 Anti Ischemia

NITRAT
B BLOKER
ANTAGONIS KALSIUM
Nitrat
 Indikasi : pada Anterior MI, iskemja persisten, CHF,
hipertensi
 Manfaat: dapat memperbaiki perfusi koroner
 Hati-hati pd: inferior MI dengan perluasan atau
keterlibatan RV
 Trials: GISSI-3 (94), ACC/AHA (96)

•Pemberian Sublingual
•Pemberian per IV
Dosis awal 5Ug/mnt ditingkatkan tiap 5 menit
disesuaikan dengan gejala klinis dan EKG
Beta-bloker
 Effektif untuk pengobatan simtomatik dan
pencegahan infark miokard.
 Vasokonstriktor moderat
– Dipilih obat yang kardio-selektif
– Berhubungan dengan nitrat.
 Kontraindikasi:vasospastik angina, blok SV derajat
II atau III, asma, gagal jantung dlm
dekompensasi,penyakit arteri perifer yg berat
Beta-bloker

Metoprolol IV 5 – 15 mg
Metoprolol oral 2 x 25 – 100 mg
Atenolol oral 1 x 25 – 100 mg
Propranolol oral 3 x 20 – 80 mg
Bisoprolol oral 1 x 5 – 10 mg
Carvedilol oral 1 x 25 mg
Antagonis kalsium

 Pd UAP atau NSTEMI bila ada indikasi kontra

B-bloker

 Tidak ada bukti manfaatnya pada pencegahan

infark miokard.

 Memberikan hasil yang baik dalam jangka

pendek pada episode iskemik.
Antagonis kalsium

Diltiazem Lepas cepat :30 -120 mg 3x/hr

Lepas lambat: 100-360 mg 1x/hr

Verapamil Lepas cepat : 40 – 160 mg/hr

Lepas lambat: 120-480 mg 1x/hr
PAIN KILLER
•Morfin:
2.5mg-5 mg IV pelan.
Hati –hati pada : inferior MCI,
asthma , bradikardia

•Pethidin : 12.5-25 mg IV pelan

ANTITROMBOTIK DAN
ANTIKOAGULAN

•Heparin ( Unfractionated Heparin)

•Low Molecular Weight Heparin
Heparin (UFH)

 Terikat pada AT III (anti-thrombin III)

,menginaktivasi trombin
 Tidak ada efek pada Factor Xa
 Hospitalization/ PTT/ bleeding
 “Benefit” in UA/ rebound effect
 Anti-Xa: Anti-thrombin 1:1
 Memperpanjang APTT
Low Molecular Weight Heparin
 Depolimerasi dari UFH standar dengan
berat molekul lebih kecil dari pada UFH
 SQ injections/ 90% bio-
available/predictable
 Anti-Xa: Anti-thrombin 2-4:1
 FDA menyetujui pemakaian enoxaparin/
dalteparin untuk SKA
UFH

LMWH
 KELEMAHAN UFH
 Bioavailability kurang baik
 Tidak dapat menghambat trombin yang terikat
pada bekuan (clot-bound thrombin)
 Tergantung pada kofaktor AT III
 Efek variabel
 Monitor APTT berkala untuk mendapatkan kadar
terapeutik
 Rebound iskemia setelah penghentian
 Risiko heparin-induced thrombocytopenia (HIT)

Panduan Terapi SKA tanpa ST Elevasi PERKI 2004

KEUNGGULAN DARI LMWH

 Mengurangi ikatan pada protein pengikat heparin

 Efek yang dapat diprediksi lebih baik
 Tidak memerlukan pengukuran APTT
 Pemakaian subkutan,menghindari kesulitan dalam
pemakaian secara IV
 Berkaitan dengan kejadian perdarahan yang kecil,
namun bukan perdarahan besar
 Stimulasi trombosit kurang dari UFH dan jarang
menimbulkan HIT
 Penghematan biaya perawatan (dari studi
ESSENCE)
TEHNIK INJEKSI LMWH SUBKUTAN
 DOSIS YANG DIREKOMENDASIKAN

UFH  Initial I.V BOLUS 60 UI/Kg max 4000 UI

 Infus :12-15 UI/kg BB/jam max 1000 UI/jam
 Monitor APTT : 3, 6, 12, 24 jam setelah mulai
terapi
 Target APTT 50-70 msec (1,5 -2 x kontrol

LMWH
Enoxaparine  1mg/kg, SC , bid
Nadroparine  0,1 ml/10 kg , SC , bid
Fondaparinu  2.5 mg
OBAT-OBATAN LAINNYA

 Tranquilizer e,g diazepam 5mg bid

 Stool softener
TERAPI FIBRINOLITIK
 Fibrinolitik : Indikasi
 Sakit dada khas IMA ≤ 12 jam
 EKG : ≥ 1 mm elevasi seg ST pada ≥ 2 sandapan yg
bersebelahan
≥ 2mm elevasi seg ST pada ≥ 2 sandapan
prekordial
Bundle branch block yg baru
 Syok kardiogenik pd IMA ( bila kateterisasi dan
revaskularisasi tdk dapat dilakukan )
• Fibrinolitik door to needle time < 30 menit !!
• PCI pada IMA lebih unggul bila dpt dilakukan
dlm 90 ± 30 menit
Fibrinolitik : indikasi kontra Absolut
 Riwayat stroke hemoragik,kapanpun terjadinya
 Riwayat stroke iskemik dalam 3 bulan kecuali stroke
iskemik dengan onset < 3 jam
 Neoplasma intrakranial
 Perdarahan internal aktif(tidak termasuk menstruasi)
 Kecurigaan suatu diseksi aorta
 Luka kepala tertutup yg signifikan atau trauma facial dalam
3 bulan
 Kelainan struktural atau pembuluh darah cerebral
 Fibrinolitik :indikasi kontra relatif
Hipertensi berat saat datang ke unit emergency yaitu BP> 180 / 110
mmHg
Pungsi vaskuler yg tak dapat dikompresi
Perdarahan internal 2 – 4 mgg sebelumnya
Konsumsi antikoagulan oral
prolonged CPR ( > 10 minutes) or operasi mayor dlm jangka waktu
2-4 minggu
Untuk Streptokinase : pemberian sebelumnya ( 5 hari-2 tahun) atau
riwayat reaksi alergi
Kehamilan
Active peptic ulcer
Riwayat hipertensi kronis yg tak terkontrol
Riwayat stroke iskemik lebih dari 3 bulan,demensia atau patologi
serebral lainnya yg blm tercantum dalam indikasi kontra
 Perbandingan terapi trombolitik
dengan terapi standar pada IMA

Mulai trombolisis Tambahan Jiwa yg

diselamatkan per 1000
pasien yg diobati
-------------------------------------------------------------------

•Pd jam pertama 65

•Pd jam kedua 37
•Pd jam ketiga 29
•Antara jam ke 3-6 26
•Antara jam 6-12 18
•Antara jam 12-24 9
AGEN FIBRINOLITIK

 Streptokinase (SK)
 Actylase (tPA)
 Reteplase (r-PA)
 Tenecteplase (TNK-tPA)
 Skema sistem fibrinolitik
Plasminogen Activators
(t-PA, u-PA)

Plasminogen Activator
Inhibitors (PA1, PA2, TAFI)

Plasminogen Plasmin

α2-Antiplasmin
Fibrin
Fibrin degradation
Product
Braunwald, A Textbook of Cardiovascular Medicine. 6th ed
SPESIFISITI FIBRIN BERBAGAI AGEN FIBRINOLITIK

 Streptokinase  Rendah
 Actylase (tPA)  Tinggi
 Reteplase(r-PA) Sedang
 Tenecteplase  Sangat tinggi
(TNK-tPA)
CARA PEMBERIAN FIBRINOLITK
 Streptokinase ( Streptase )
1.5 million Unit in 100 ml D5W or 0.9% saline
selama 30-60 mnt
without heparin : Inferior MCI
with heparin : anterior MCI
 tPA
15 mg IV bolus kemudian 0.75 mg/Kg selama 30
mnt,dilanjutkan 0.5 mg/Kg selama 60 mnt
berikutnya
Streptokinase (SK, Streptase)

 Keuntungan : lebih baik pada anterior

MCI, age <75; lebih murah
 Komplikasi: antigenic, perdarahan
intraserebral pada studi GUSTO 0.6%
 Trials: GISSI-1, ISIS-2 (88)