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Obat Lipidemik: Dept of Pharmacology and Therapeutics FK Undip Oktober, 2018
Obat Lipidemik: Dept of Pharmacology and Therapeutics FK Undip Oktober, 2018
1-4
29-5
Hypolipidemic Drugs
1-6
Serum Cholesterol and
Cardiovascular Risk
18
6 year CHD death rate per 1,000 men
16
14
12
10
8
6
4
2
0
140 160 180 200 220 240 260 280 300 mg/dL
4.5 5.5 6.5 7.5 mmol/L
Serum cholesterol
Martin. Lancet 1986;933–936
29-9
• The liver
makes two-
thirds of the
daily
cholesterol
requirement
.
‡Statin therapy may be considered if risk decision is uncertain after use of ASCVD risk
calculator
Intensity of Statin Therapy
*Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice. There
might be a biologic basis for a less-than-average response.
†Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in IDEAL (Pedersen et al).
‡Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not
recommended by the FDA due to the increased risk of myopathy, including rhabdomyolysis.
Side Effects Statin
Management of Muscle
Symptoms on Statin Therapy
• It is reasonable to evaluate and treat muscle
symptoms including pain, cramping, weakness, or
fatigue in statin-treated patients according to the
management algorithm
• Ezetimibe:
– Modestly reduces total cholesterol, LDL,
and triglyceride blood levels
– Ideal to combine with other hypolipidemic
drugs
– Adverse effects—abdominal pain, fatigue,
coughing, diarrhea, back pain, and
arthralgia
29-25
Fibrates enhance the oxidation of fatty acids (FA) in liver and muscle and reduce the
rate of lipogenesis in the liver, thereby reducing hepatic secretion of very-low-
density lipoprotein (VLDL) triglycerides (TG).
The increased uptake of triglyceride-derived fatty acids in muscle cells results from
an increase in lipoprotein lipase (LPL) activity in adjacent capillaries and a decrease
in the apolipoprotein CIII (Apo CIII) concentration mediated transcriptionally by
peroxisome proliferator-activated receptor a (PPARa).
Side Effects
5. Inhibitor of VLDL secretion and
lipolysis
• Niacin (Nicotinic acid)
Nicotinic Acid
• MOA—affects cholesterol synthesis through a
G proteins coupled receptor:
– Inhibits triglyceride lipase
– Stimulates lipoprotein lipase
– Decreases free fatty acid release and removes
triglycerides
• IND—hyperlipidemia
• Adverse effects—flushing, nausea, vomiting,
and diarrhea
Nicotinic acid inhibits the mobilization of free fatty acids (FFA) from peripheral
adipose tissue to the liver. As a consequence of this decrease or an additional
hepatic effect, the synthesis and secretion of very-low-density lipoprotein (VLDL)
are reduced, and theconversion of VLDL to low-density lipoprotein (LDL) is
decreased.
Nicotinic acid can also increase serum high-density lipoprotein (HDL) cholesterol
concentrations by up to 30 percent; the mechanism responsible for this effect is
unknown.
Robert H. Knopp, M.D. N Engl J Med 1999; 341:498-511
Side Effects
Fish oil derivative
• Omega-3-fatty acids
• Eicosa-pentanoic and docosa-hexanoic acid
• Prophylaxis use in high risk patient of CAD
• Usually formulated with vit.E
Combination drug therapy
• Bile acid binding resins+Fibrates
• Bile acid binding resins+Niacin
• Bile acid binding resins+Statins
• Bile acid binding resins+Niacin+ Statins
• Niacin+Statin (Atorva 10+ Nia 500)
• Statins+Ezetimibe (OK)
• Statins+Fibrate (Careful, better avoid)
6. PCSK9 inhibitor
This should
increase the
clearance of LDL
cholesterol from
the circulation.
10
UC LDL-C Percent Change
0
-10
-20 Treatment difference
57%
-30
-40
-50
-60 -51.5%
-70
Number of patients:
-80
302 294 264
599 582 542