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• Plasma lipids consist mostly of lipoproteins, which are spherical complexes of lipids
and specific proteins (apolipoproteins).
• Clinically important lipoproteins, listed in decreasing order of atherogenicity, are:
LDL, VLDL , chylomicrons, HDL.
• The occurrence of CHD is positively associated with high total cholesterol and with
elevated LDL-C.
• Total cholesterol is the sum of LDL-C, VLDL-C, and HDL-C.
• high levels of HDL-C have been associated with a decreased risk for heart disease.
Reduction of LDL-C is the primary goal of cholesterol-lowering therapy.
• Previously, cholesterol guidelines recommended treating to specific
targets for LDL- C.
• Recent cholesterol guidelines do not recommend targets but instead
emphasize high-intensity or moderate-intensity statin therapy in
defined populations with risk for atherosclerotic cardiovascular
disease (ASCVD).
• Higher-intensity therapy is recommended in those with established
ASCVD or in those with a higher overall risk of heart disease
• Chylomicrons carry triglycerides from the intestines to the liver,
to skeletal muscle, and to adipose tissue.
• VLDL carry (newly synthesised) triglycerides from the liver to adipose
tissue.
• IDL are intermediate between VLDL and LDL. They are not usually
detectable in the blood when fasting.
• LDL carry 3,000 to 6,000 fat molecules (phospholipids, cholesterol,
triglycerides, etc.) around the body. LDL particles are sometimes
referred to as "bad" lipoprotein because concentrations, dose related,
correlate with atherosclerosis progression.
• HDL collect fat molecules (phospholipids, cholesterol, triglycerides)
from the body's cells/tissues, and take it back to the liver. HDLs are
referred to as "good" lipoprotein because higher concentrations
correlate with low rates of atherosclerosis progression.
Metabolism of plasma lipoproteins
Treatment options for hypercholesterolemia
Adverse effects:
• an intense cutaneous flush and pruritus.
• Administration of aspirin prior to taking niacin decreases
the flush,
• Slow titration of the dosage
3. Fibrates
• Fenofibrate
• gemfibrozil,
• benzafibrate
are derivatives of fibric acid that lower serum TG and
increase HDL levels.
Mechanism of action:
• The peroxisome proliferator–activated receptors (PPARs) are
members of the nuclear receptor family that regulates lipid
metabolism.
• Upon binding to their natural ligands (fatty acids or
eicosanoids) or antihyperlipidemic drugs, PPARs are activated.
Pharmacokinetics:
• Gemfibrozil and fenofibrate are completely absorbed after
oral administration and distribute widely, bound to albumin.
• Fenofibrate is a prodrug, which is converted to the active
moiety fenofibric acid.
Adverse effects:
• mild gastrointestinal disturbances. These lessen as the therapy
progresses. Because these drugs increase biliary cholesterol excretion,
there is a predisposition to form gallstones.
• Myositis (inflammation of a voluntary muscle) can occur, and muscle
weakness or tenderness should be evaluated.
• may increase the effects of warfarin.
• Fibrates should not be used in patients with severe hepatic or renal
dysfunction or in patients with preexisting gallbladder disease.
4. Bile acid–binding resins
Bile acid–binding The resin/bile acid complex lowering the bile acid GIT disturbance
resins concentration.
increase conversion of cholesterol to bile acids
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