Used in Hyperlipoproteinemias

LDL particles carry the apolipoprotein B-100, by which they are bound to receptors that mediate uptake of LDL into the cells, including the hepatocytes (receptor-mediated endocytosis, p. 26). 

HDL particles are able to transfer cholesterol from tissue cells to LDL particles. In this way, cholesterol is transported from tissues to the liver. 

Hyperlipoproteinemias can be caused genetically (primary hyperlipoproteinemia) or can occur in obesity and metabolic disorders (secondary hyperlipoproteinemia). Ele- 

Lipoprotein metabolism. Enterocytes release absorbed lipids in the form of trigly-ceride-rich chylomicrons. Bypassing the liver, these enter the circulation mainly via the lymph and are hydrolyzed by extrahepatic endothelial lipoprotein lipases to liberate fatty acids. The remnant particles move on into liver cells and supply these with cholesterol of dietary origin. 

The liver meets the larger part (60%) of its requirement for cholesterol by synthesis de novo from acetyl-coenzyme A. Synthesis rate is regulated at the step leading from hydroxymethylglutaryl-CoA (HMG-CoA) to mevalonic acid (p.l61A), with HMG-CoA reductase as the rate-limiting enzyme. 

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BARs are useful in treating primary hypercholesterolemia (familial hypercholesterolemia, familial combined hyperlipidemia, type Ila hyperlipoproteinemia). 

The standard diet used in our experiments is a semipurified, cholesterol-free preparation that is composed of 25% protein, 40% sucrose, 13% coconut oil, 1% corn oil, 15% cellulose, 5% mineral mix, and 1% vitamin mix. This diet has been shown to induce an endogenous hypercholesterolemia and lead to atherosclerosis in rabbits and monkeys (4, 5). The specific question addressed by our series of investigations is whether the type of dietary protein, when all other dietary components are constant, can influence the development of hyperlipoproteinemia and atherosclerosis. More specifically, we have examined the effects of the individual amino acids, lysine and arginine, and their ratios in the diet on plasma and hepatic lipids as well as the development of arterial plaques. 

The bile acid sequestering resins lower elevated LDL cholesterol and therefore are useful in the treatment of type Ila hyperlipoproteinemia. However, because the resins can raise plasma VLDL in some patients, they are not recommended for treatment of combined hyperlipidemias (type Ilb) when both LDL cholesterol and VLDL triglycerides are high or in other conditions of elevated triglycerides. 

They are useful only in hyperlipoproteinemias involving elevated levels of LDL i.e. type Ila, lib and V. They are basic ion exchange resins. They are neither digested nor absorbed in the gut. They bind bile acids in intestine and interrupt their entero-hepatic circulation, leading to increased faecal excretion of bile salts and cholesterol. There is increased hepatic conversion of choles-terol to bile acids. More LDL receptors are expressed on liver cells leading to increased clearance of IDL, LDL and indirectly of VLDL. 

This synergistic combination is useful in the treatment of familial hypercholesterolemia but may not control levels of VLDL in some patients with familial combined hyperlipoproteinemia. Statins should be given at least 1 hour before or 4 hours... 

Therapeutic uses Niacin lowers plasma levels of both cholesterol and triacylglycerol. Therefore, it is particularly useful in the treatment of Type lib and IV hyperlipoproteinemia, in which both VLDL and LDL are elevated. Niacin is also used to treat other severe hypercholesterolemias, often in combination with other antihyperlipidemic agents (see p. 215). In addition, it is the most potent antihyperlipidemic agent for raising plasma HDL levels. 

Cholestyramine resin is the drug of choice for type lla hyperlipoproteinemia. When used in conjunction with a con-iFullcd diet, it reduces lipoproteins. The drug is an insoluble polymer and. thus, probably one of the safest because it is not absorbed from the gastrointestinal tract to cause systcmic losic effects. 

The opposite error can occur if the Friedewald equation is used in patients with type III hyperlipoproteinemia. Type III hyperlipoproteinemia is characterized in part by the presence of p-VLDL, not normally present in the blood. Biochemically, p-VLDL occurs in the VLDL, density range, but is much richer in cholesterol than normal VLDL with a ratio of triglyceride/cholesterol on the order of 3 1. Application of the factor [triglyceride]/5 in type Ills would underestimate VLDL cholesterol and in turn overestimate LDL cholesterol. Thus a patient with type III hyperlipoproteinemia may appear to have an artifactually high LDL cholesterol concentration. 

Medium-chain triglycerides, unlike other saturated fats, do not contribute to a rise in blood cholesterol. Hence, they are used in the treatment of some hyperlipoproteinemias. 

Type III hyperlipoproteinemia may be associated with increased VLDL production and abnormal elimination of VLDL remnants. Bile acid and cholesterol synthesis appear to be within normal limits. However, the use of the isotopic technique has indicated that bile acid production is about twice that in hyperlipoproteinemia type II and is not different from that in type IV. 37 cholesterol synthesis may have been within the... 

Nicotinic acid in large doses used to treat hyperlipoproteinemia causes a cutaneous flush. The vasodilator) effect is due to... 

Carnitine Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH]... 

Treatment Various drugs are available that have different mechanisms of action and effects on LDL (cholesterol) and VLDL (triglycerides) (A). Their use is indicated in the therapy of primary hyperlipoproteinemias. In secondary hyperlipoproteinemias, the immediate goal should be to lower lipoprotein levels by dietary restriction, treatment of the primary disease, or both. 

The laboratory must be informed when the therapeutic regimens include drugs specifically administered to change the blood level of a biochemical constituent. Cholestyramine resin, a nonabsorbable anion exchange resin administered orally to patients with hyperlipoproteinemia produced a 24% decline in serum cholesterol levels in 14 patients with essential hypercholesterolemia. In these patients the mean cholesterol fell from 414 98 mg/100 ml to 176 21 mg/100 ml (FI). Pectin added to the diet caused a 5% decrease in serum cholesterol values (K4), as did an oral hydrophobic colloid (G4). Levels fell in one case from 220 mg/ 100 ml to 160 mg/100 ml (G4). Nicotinic acid, neomycin, and p-chloro-phenoxyisobutyrate have all been used to reduce serum cholesterol (G7). 

It is considered the most effective drug for lowering levels of cholesterol, triglycerides, and very low-density lipoproteins in the plasma and for moderately increasing the number of high-density lipoproteins. It is used for treating hyperlipoproteinemia that cannot be corrected by a special diet or physical exertion. Synonyms of lovastatin are lovalip, meva-cor, mevinacor, and sivlor and those of mevastatin are CS-500 and ML-236 B. 

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