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Hyperlipidemia
Hyperlipidemia and hyperlipoproteinemia are general terms for elevated
concentrations of lipids and lipoproteins in the blood.
hypercholesterolemia
and hypertriglyceridemia
refer specifically to
elevated concentrations of cholesterol and triglycerides, respectively.
Hypercholesterolemia contributes to the pathogenesis of atherosclerosis,
coronary artery.
Hypertriglyceridemia is associated with pancreatitis and have role in the
development of atherosclerosis and heart disease in some patients.
Lipoproteins and Lipid Transport:
Because lipids are insoluble in plasma, they must be transported
in the circulation in the form of lipoproteins. There are many
types
of
lipoproteins;
lipoproteins
(VLDL),
intermediate-density
chylomicrons,
low-density
lipoproteins
very
low
density
lipoproteins
(LDL),
(IDL),
high-density
lipoproteins (HDL), and lipoprotein (a). The various types are
distinguished in terms of their density, lipid and protein
composition, and role in lipid transport.
Management of Hyperlipidemia:
Modifications of diet:
Dietary modifications are the cornerstone of treatment for
hyperlipidemia and may be effective by themselves in
patients with mildly elevated cholesterol or triglycerides.
The diet of patients with hypercholesterolemia should be low in
cholesterol, saturated fat, and calories.
In some patients with hypertriglyceridemia, supplementing the
diet with fish oils that contain omega-3 fatty acids may be
useful in lowering the triglyceride levels.
Classification of drugs for hyperlipidemia
I- Drugs for hypercholesterolemia
1- HMG-CoA reductase inhibitors: Atorvastatin – Lovastatin.
2- Bile acid-binding resins: Cholestyramine – Colestipol.
II- Drugs for hypercholesterolemia and hypertriglyceridemia
a- Fibric acid derivatives: Bezafibrate - Fenofibrate.
b- Miscellaneous drugs and natural compounds
- Niacin, Nicotinic acid
- Vitamin E and other antioxidants
- Probucol
- Estrogens
HMG-CoA Reductase Inhibitors
They are structurally related to 3-hydroxy-3-methylglutaryl-coenzyme
A which is converted by HMG-CoA reductase to mevalonic acid,
reducing hepatic cholesterol biosynthesis. This increases the
number of hepatic LDL receptors and enables more LDL to be
delivered to the liver. As a result, there is a reduction in the level of
LDL cholesterol in the serum. They also reduce serum triglycerides.
The HMG-CoA reductase inhibitors are used for the treatment of
hypercholesterolemia. They are relatively free of adverse effects,
but they may elevate hepatic enzymes and cause hepatitis.
frequently, they cause myalgia and rhabdomyolysis.
Less
Bile Acid-Binding Resins
They have excellent safety record and are valuable for patients cannot tolerate
other drugs and young patients who may need to take drug long time.
The bile acid-binding resins are large polymers containing Cl- that can be
exchanged for bile acids in the gut. The bile acid-resin complex is excreted
in feces. This action prevents the enterohepatic cycling of bile acids and
obligates the liver to synthesize replacement bile acids from cholesterol. To
obtain more cholesterol for this purpose, the liver increases the number of
LDL receptors. Then the levels of LDL cholesterol in the serum are reduced
as more cholesterol is delivered to the liver.
They may cause constipation and they can bind, In the gut, to digoxin, thyroxin,
warfarin, and other drugs.
Fibric Acid Derivatives
They activate lipoprotein lipase, promoting the
delivery of triglycerides to
adipose tissue. They also interfere with the formation of VLDL in the liver.
They
cause
rhabdomyolysis
and
myopathies.
For
this
reason,
the
combination of reductase inhibitors and fibrates should be avoided.
Niacin (nicotinic acid)
Niacin is a vitamin, converted in the body to enzyme cofactors (NAD and NADP)
required for oxidative reactions in intermediary metabolism. The quantity of
ingested in food does not have effect on serum lipids. The action on lipids
requires the administration of several grams of niacin each day. These large
doses reduces hepatic VLDL secretion and enhances VLDL clearance by
activating lipoprotein lipase.
Niacin is probably the most effective single drug for mixed hyperlipidemia.
Niacin can elevate serum transaminases and cause hepatitis. It may activate
peptic ulcer. Niacin may aggravate diabetes.
Estrogens
-Estrogens have been demonstrated to protect women against atherosclerosis,
largely by increasing HDL cholesterol levels.
Vitamin E and Other Antioxidants
Vitamin E and other naturally occurring antioxidants may have a protective
effect against atherosclerosis by preventing the oxidation of LDL cholesterol.