Lipid levels agents lowering

The discovery of the statin mevalonic acid synthesis inhibitors focused new attention on control of blood lipid levels as a measure to stave off heart disease. A number of compounds have been found that treat elevated lipid levels by other diverse mechanisms. The phosphonic acid derivative ibrolipim (9) is believed to lower those levels by accelerating fatty acid oxidation. The phosphoms-containing starting material 7 can in principle be obtained by the Arbuzov reaction of a protected from of p-bromomethylbenzoic acid (6) with triethyl phosphate. Removal of the protecting group and conversion of the acid to an acyl chloride then affords 7. Condensation of this intermediate with substituted aniline 8 leads to the hypolipidemic agent (9). ... 

Since lipid (lipoprotein) inhibit lysis, agents that lower lipid levels have a normalizing effect on decreased fibrinolysis activity due to elevated lipids. Even the removal of normal lipid content from plasma with chloroform increases lysis activity. Vasoactive agents have previously been reported61 to stimulate activator release resulting in enhanced lysis activity of short duration. 

Drug therapy is generally reserved for patients who fail to respond to diet or other measures described above. Lipid-lowering agents are described in Table 4.8. Strategies for reducing lipid levels include ... 

Cloflbrate and related compounds have been used extensively as lipid lowering agents in patients with various forms of Iqrperlipemia and atherosclerosis. In addition to lowering serum lipid levels, these compounds have been reported to affect all three aspects of the problem of thrombosis being considered in this review. Two recent reports further describe the ability of these compounds to decrease FA in hyperlipemic patients. 27,28... 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

Older primary prevention trials had often been undertaken in cohorts at low absolute risk of CHD events. The initial secondary prevention studies had typically involved patients with elevated cholesterol levels. In addition, these older trials had tested diet and previous lipid-lowering agents, which only lowered cholesterol by an average of approximately 10% (5). As a consequence, these trials were typically underpowered and had not shown a clear reduction in all-cause mortality. There had been good evidence that lipid-modifying therapy could prevent fatal and nonfatal CHD events (5). However, there were some concerns that noncardiovascular events particularly related to cancers and violence or trauma could be increased. In summary, there was considerable uncertainty about the overall effects of treatment. 

Several workers have shown that a high concentration of ascorbic acid added to liquid milk inhibits oxidation. Chilson (1935) suggested that added ascorbic acid acts as a reducing agent, which is oxidized more readily than milk fat. Bell et al. (1962) suggested that addition of L-ascorbic acid to cream produced a medium less conducive to oxidation by lowering the oxidation-reduction potential. Addition of an adequate level of surface-active ascorbyl palmitate to milk products may retard lipid oxidation by orientation at the lipid-aqueous interface where it intercepts free radicals (Badings and Neeter, 1980). 

---