Hipolipidemic

Oleh
Nurhidayatunnisak (1800084)
Kelas D3 3B

Dosen pembimbing : Novia Sinata, M.Si., Apt

 Definition
• Hipolipidemic is drug used to reduce plasma
lipid levels.
• This drug is aimed at reducing plasma lipid
levels to reduce the risk of atherosclerotic
disease.
• Before giving lipid-lowering drugs, it is
necessary to know the secondary cause (ex;
diabetes mellitus) to determine the type of
hypolipidemic.
 Artheriosclerotic
• a disease characterized by loss of elasticity of the
arterial wall.
• there are three types, namely atherosclerosis,
arteriosclerosis monckeberg, and arteriolarosclerosis.
• atherosclerosis is the most common, characterized by
the presence of cholesterol, lipoid substances and
lipofags in the arteries which can cause blockages so
that blood flow is obstructed to the organs of the body.
 Lipid plasma
• cholesterol, triglycerides, phospholipids and
free fatty acids.
• so that plasma lipids can be transported in
circulation, the composition of lipid molecules
is modified in the form of water-soluble
lipoproteins.
• treatment is directed at correcting lipoprotein
abnormalities, not just reducing total
cholesterol and plasma triglyceride levels.
 lipoprotein
• The bond between fat (cholesterol, triglycerides, and
phospholipids) with this protein is called lipoprotein.
• Lipoprotein has the duty to transport lipids from the
place of synthesis to the place of use, while
apolipoprotein has the duty to maintain the structure
of lipoprotein.
• Based on the composition, density, and mobility,
lipoproteins can be divided into chylomicrons, very low
density lipoprotein(VLDL), low density lipoprotein(LDL),
dan high density lipoprotein(HDL).
1. Chylomicrons
chylomicrons are the largest molecular weight lipoproteins
(80% triglycerides and <5% ester cholesterol). Chylomicrons
carry triglycerides from food to skeletal fat and muscle tissue,
also carry food cholesterol to the liver.

2. Very Low Density Lipoprotein(VLDL)

lipoprotein which consists of 60% triglycerides and 10-15%
cholesterol. VLDL is secreted by the liver to transport
triglycerides to peripheral tissues. VLDL triglycerides produce
free fatty acids to be stored in adipose tissue and oxidizing
agents in the heart and skeletal muscles.
3. Low Density Lipoprotein(LDL)
Lipoprotein contains as much as 10% triglycerides and 50%
cholesterol. lipoprotein that carries cholesterol from the liver
to all body tissues that need it, especially as a raw material for
the formation of cell walls and hormones. This LDL causes
blood vessel constriction.

4. High Density Lipoprotein(HDL)

HDL levels are relatively stable in adults, which is around 45
mg / dL in men and 54 mg / dL in women. Inversely
proportional to postmenopausal women HDL levels up to 20%
compared to men. HDL contains 25% cholesterol level
 Hypolipidemic drug classification
Hypolipidemic drugs can be divided into four on
the mechanism of action:

• Inhibitors of intestinal sterol absorption

• Competitive inhibitors of hmg-coa reductase
• Bile Acid sequstranst
• Niacine
• Fibrate
1. COMPETITIVE INHIBITORS OF HMG-COA REDUCTASE
(REDUCTASE INHIBITORS; “STATINS”)
• These compounds are structural analogs of HMG-CoA. Lovastatin,
atorvastatin, fluvastatin, pravastatin, simvastatin, rosuvastatin, and
pitavastatin belong to this class. They are most effective in reducing
LDL.
• Other effects include decreased oxidative stress and vascular
inflammation with increased stability of atherosclerotic lesions.
• The active forms of the reductase inhibitors are structural analogs
of the HMG-CoA intermediate that is formed by HMG-CoA
reductase in the synthesis of mevalonate. These analogs cause
partial inhibition of the enzyme and thus may impair the synthesis
of isoprenoids such as ubiquinone and dolichol and the prenylation
of proteins. It is not known whether this has biologic significance.
This effect increases both the fractional catabolic rate of LDL and
the liver’s extraction of LDL precursors (VLDL remnants) from the
blood, thus reducing LDL
• Daily doses of lovastatin (Cholvastin, Justin, Lotyn, Lovatrol,
Lipovas, Lofacol dan Lotivas) vary from 10 to 80 mg.
• Pravastatin (Cholespar, Koleskol, Pravinat, Gravastin dan
Novales) is nearly as potent on a mass basis as lovastatin
with a maximum recommended daily dose of 80 mg.
• Simvastatin (Simvastatin, Simbado, Sintrol, Selvim, Statcol,
Statkoles, Norpid, Mersivas, Valemia) is twice as potent and
is given in doses of 5–80 mg daily. Because of increased risk
of myopathy with the 80 mg/day dose
• Toxicity
Minor increases in creatine kinase (CK) activity in plasma are observed in some
patients receiving reductase inhibitors, frequently associated with heavy physical
activity. Rarely, patients may have marked elevations in CK activity, often accompanied
by generalized discomfort or weakness in skeletal muscles. If the drug is not
discontinued, myoglobinuria can occur, leading to renal injury. Myopathy may occur
with monotherapy, but there is an increased incidence in patients also receiving
certain other drugs.

• Indications
This medicine works by reducing the amount of cholesterol made by the liver.
Lowering "bad" cholesterol and triglycerides and increasing "good" cholesterol lowers
the risk of heart disease and helps prevent strokes and heart attacks

• Contra Indicaions
Hypercholesterolemia (high cholesterol levels in the blood), Familial Homozygotes -
less effective in patients with this condition active liver disease, Hypotension (low
blood pressure).
 2. INHIBITORS OF INTESTINAL STEROL ABSORPTION

• Ezetimibe is the first member of a group of drugs that inhibit

intestinal absorption of phytosterols and cholesterol. Its primary
clinical effect is reduction of LDL levels.
• Ezetimibe is a selective inhibitor of intestinal absorption of
cholesterol and phytosterols. A transport protein, NPC1L1, appears
to be the target of the drug. It is effective even in the absence of
dietary cholesterol because it inhibits reabsorption of cholesterol
excreted in the bile.
• Dose
The effect of ezetimibe on cholesterol absorption is
constant over the dosage range of 5–20 mg/d. Therefore,
a single daily dose of 10 mg is used.
• Toxicity
Ezetimibe does not appear to be a substrate for
cytochrome P450 enzymes. Experience to date reveals a
low incidence of reversible impaired hepatic function
with a small increase in incidence when given with a
reductase inhibitor. Myositis has been reported rarely.
 3. FIBRATE

• Fibrates are useful drugs in hypertriglyceridemias in which

VLDL predominate and in dysbetalipoproteinemia. They
also may be of benefit in treating the hypertriglyceridemia
that results from treatment with viral protease inhibitors.
• The usual dose of gemfibrozil is 600 mg orally once or twice
daily. The dosage of fenofibrate (as Tricor) is one to three
48 mg tablets (or a single 145 mg tablet) daily
• Toxicity
Rare adverse effects of fibrates include rashes, gastrointestinal
symptoms, myopathy, arrhythmias, hypokalemia, and high
blood levels of aminotransferases or alkaline phosphatase
1. Fenofibrate
• Trademarks: 200 M Profibrate, Fenofibrate, Fibesco, Yosenob 300, Fenolip.
Lipanthyl, Fibramed 300, Trolip, Hicholfen, Hyperchol, Lidose phenoids,
Evothyl, Zumafib, Noles, Cholecaps, Lipofibrat
• Dose
For capsules form fenofibrate, the dose is 150 mg, once a day. As for the
tablet form, the dosage is 120-160 mg, once a day.
• Indications
Fenofibrate can used to prevent the risk of pancreatitis in patients who have
high triglycerides (fat in the blood).
• Contra Indications
1. patients with severe renal impairment, including those receiving dialysis
2. patients with active liver disease, including those with primary biliary
cirrhosis and unexplained persistent liver function abnormalities
 4. NIACINE

• Niacin inhibits VLDL secretion, in turn decreasing

production of LDL. Increased clearance of VLDL contributes
to reduction of triglycerides. Niacin has no effect on bile
acid production.
• Niacin inhibits the intracellular lipase of adipose tissue via
receptor-mediated signaling, possibly reducing VLDL
production by decreasing the flux of free fatty acids to the
liver.
• Toxicity
Most persons experience a harmless cutaneous vasodilation
and sensation of warmth after each dose when niacin is
started or the dose increased. Hyperuricemia occurs in some
patients and occasionally precipitates gout.
• Dose
hypercholesterolemia, most patients require 2–6 g of niacin daily; For
other types of hypercholesterolemia and for hypertriglyceridemia, 1.5–
3.5 g daily is often sufficient.
• Indications
Niacin (Niacin acid) is a drug used to prevent and treat niacin
deficiency (pellagra) and and decrease cholesterol levels in the blood.
• vitamin B3 supplements at doses of more than 3 grams per day can
cause serious side effects such as liver disease, gout, stomach
ulcers, vision problems, increased blood sugar levels, and
arrhythmias.
 5. BILE ACID-BINDING RESINS

• Resin works by lowering cholesterol levels by

increasing bile acids in the digestive tract,
interfering with enterohepatic circulation so that
the excretion of acidic steroids in the stool
increases.
• Colestipol and cholestyramine are available as
granular preparations. A gradual increase of
dosage of granules from 4 or 5 g / d to 20 g / d is
recommended. Total dosages of 30-32 g / d may
be needed for maximum effect.
1. Cholestyramine
• Cholesterol-lowering drugs from binder types of bile acids or also called
resins. This drug is used to reduce excess cholesterol in the body, normal
cholesterol conditions will reduce the risk of heart disease and stroke.

• Dossage
Hypercholesterolemia, heart disease, diarrhea due to bile latex Adult dose: 4
grams per day increases 4 grams every week to 12-24 grams per day divided
into 1-4 doses, also can be adjusted according to needs. Maximum use of 36
gr per day.
• Indications
The resins are used in treatment of patients with primary
hypercholesterolemia, producing approximately 20% reduction in LDL
cholesterol in maximal dosage
• Contra Indications
Experience total bile obstruction. Have a history of allergy to this drug.
2. Colestipol
• Dossage
Colestipol is also available in 1 g tablets that must be swallowed whole,
with a maximum dose of 16 g daily. Colesevelam is available in 625 mg
tablets and as a suspension (1875-mg or 3750-mg packets). The
maximum dose is six tablets or 3750 mg as suspension, daily.

• Indications
The resins are used in treatment of patients with primary
hypercholesterolemia, producing approximately 20% reduction in LDL
cholesterol in maximal dosage
• Contra Indications
Experience total bile obstruction. Have a history of allergy to this drug.