• Lipids of human plasma are transported as
complexes with proteins, such macromolecular
complexes are termed lipoproteins; except fatty
acids which are bound to albumin.
• Any metabolic disorders involving the elevations
in plasma concentrations of any lipoprotein
species known as hyperlipoproteinemias or
• Hyperlipidemia is generally restricted to
conditions that involve increased level of
triglycerides in plasma.
• The major complications are acute
pancreatitis and atherosclerosis
• Those which contain apolipoprotein (apo)
B100 act as vehicles by which cholesterol are
transported into artery wall.
• Those are low-density (LDL), intermediate
density (IDL), very low density (VLDL) and
• Cellular components in atherosclerotic plaque
are foam cells, derived form macrophages and
smooth muscle cells filled with cholesteryl
• The atheromatous plaque grows over time
with the accumulation of increased no. of
foam cells and of collagen and fibrin.
• High-density lipoproteins (HDL) exert antiatherogenic effects.
1) Cigarette is a major risk factor for coronary disease
– Associated with reduced HDL levels
– Impaired cholesterol level
– Cytotoxic effects on endothelium
– Increased oxidation of atherogenic lipoproteins
– Stimulates thrombogenesis
4) LDL levels
• Normally EDRF, nitric oxide are responsible for
vessels regulation but it is impaired in
• So natural antioxidants such as tocopherol and
ascorbic acid can reduce such impairment.
Major lipoproteins are:
Cholesteryl esters and
A monolayer of unesterified cholesterol and phospholipids
surrounds the hydrophobic core of above lipoproteins.
• Specific proteins (apolipoproteins) are located on the
• Also certain lipoproteins contain large mol. wt
apolipoproteins(B lipoproteins) which don’t migrate like
• Subtypes of B apolipoproteins:
B-48 formed in intestine with chylomicrons
B100 synthesized in liver and found in VLDL, VLDL
remnants,LDL and the Lp(a) lipoproteins.
– Lagest type;formed in intestine and carry dietary lipids
– Responsible for transport of lipids
• Very low density lipoproteins (VLDL) :
– Secreted by liver; means for transporting triglycerides
to peripheral tissues
– Hydrolyzed by lipoprotein lipase yielding free fatty
acids for oxidation and storage.
– Intermediate particles called IDL are formed after the
VLDL is depleted of triglycerides.
• Low density lipoproteins:
– Further removal of triglycerides by hepatic
lipaseresults in its formation.
– Hepatocytes play a major role for its catabolic
• Lp(a) lipoprotein:
– Formed form an LDL-like moiety
– The Lp(a) lipoprotein complex can be found in
atherosclerotic plaques and contribute to
coronary disease by inhibiting thrombolysis.
• High density lipoproteins:
– Secreted by the liver and intestine
– Comes from surface of chylomicrons and VLDL
• Atherosclerosis: It is a disease which affects large and
medium size arteries, and a leading cause of death.
• consists of localized plaque in the intima, and is
composed of cholesterol esters, proliferation of
smooth muscle, deposition of fibrous proteins and
– Narrowing of the arterial lumen
– Ulceration of arterial lumen and thrombosis of artery and
– Weakens arterial wall and formation of aneurysms.
HMG-CoA reductase inhibitors
• Mechanism of action
The de novo synthesis of cholesterol involves a
pathway in which mevalonic acid is formed and by the
enzyme hydroxymethylglutaryl co-enzyme reductase
(HMG-Co A reductase); the statins inhibits this step
resulting in decrease hepatic cholesterol synthesis.
Resultantly synthesis of high affinity LDL receptors on
the liver occurs and increased clearance of plasma LDL.
• Decrease liver cholesterol
• Increase LDL gene expression
• Decrease plasma LDL
• Decrease VLDL synthesis
• Decrease TGLs
– Given orally except fluvastatin
– Upto 90% available
– Undergoes first pass metabolism and secreted in
– 5-10% excreted in urine
• Adverse effects:
Headache, nausea, bowel upsets, rashes
Myalgia , myopathy
Rise in LFTs particularly serum transaminases
– Hyperlipidemia with raised LDL and Cholesterol level
– Progression of atherosclerotic lesion
– Ischemic heart disease of elderly
• Also known as bile acid binding resin.
• Bile acid binding resins are cholesterol lowering
drugs that are man made resins. They are gritty,
insoluble granules which are available in the form
of a bar that has to be chewed thoroughly or
comes in the form of a powder and needs to be
mixed with a liquid.
• These prevent re-absorption of cholesterol into
the body when they bind with the cholesterolrich bile acids secreted by the liver.
• Resulting in decreased enterohepatic
circulation of causing the liver to increase
production of bile acids utilizing cholesterol
• Decrease LDL levels
• Increase LDL receptor gene expression.
• It significant effect on LDL levels by utilizing
the LDL receptors but no effect on the HDL
– Orally (chewed)
– No systemic effects as it is retained in the GI tract
– Usual dose of 12-36g of resin per day in divided
doses with meals.
– Increased VLDL and triglycerides
– Usually causes GI symptoms like constipation and
– May interfere with the absorption of fat-soluble
vitamins and may bind with other drugs if taken
– Orally administered drugs
Fibric acid derivatives
• Prototype: Gemfibrozil
• Others : clofibrate , benzafibrate
• Mechanism of action:
– Induction of lipoprotein lipase
– Activation of the nuclear transcription receptor
“peroxisome proliferator - activated receptor alpha” (PPARα). –mediate effects of insulin
– class of intracellular receptors that modulate carbohydrate
and fat metabolism and adipose tissue differentiation.
– PPAR-α activation by fibrates results in numerous changes
in lipid metabolism that act together to decrease plasma
triglyceride levels & increase plasma HDL.
– Decrease VLDL and IDL
– Hypertriglyceridemias in which VLDL predominate
& in dysbetalipoproteinemia.
– Treatment of hypertriglyceridemia resulting from
treatment with viral protease inhibitors.
– absorbed from the GI tract & undergoes
– most (70%) is eliminated unchanged through the
– half life : 1.5 hrs.
• Side Effects:
rare cases of rash
High aminotransferase or alkaline phosphatase levels,
risk of cholesterol gallstones.