Hypercholesterolemia high blood cholesterol treatments

Drugs that inhibit HMG-CoA reductase have been developed for the treatment of hypercholesterolemia (high blood cholesterol). These drugs are based on a class of fungus-derived molecules called statins. One such chemical stmcture is shown in Fig. 12-12 note how part of the molecule is similar in shape to HMG-CoA, and it is via this moiety that it binds to HMG-CoA reductase. 

HMG CoA reductase can be inhibited therapeutically by administering the drug lovastatin, based on the fungal products mevinolin and compactin, which competitively inhibit the enzyme and hence decrease the rate of cholesterol biosynthesis. Therefore, these compounds are routinely used for the treatment of hypercholesterolemia (high levels of blood cholesterol) (see Topic K6). 

The causal relationship between low bile acid production and high serum cholesterol in familial hypercholesterolemia remains unknown. It can be postulated that they are not associated initially, particularly because augmented conversion of cholesterol to bile acids is not able to normalize the serum cholesterol level. On the other hand, it can be speculated that cholestyramine treatment, for instance, stimulates cholesterol production by hepatocytes so that subnormal amounts of newly synthesized cholesterol are utilized for bile acid synthesis, a relatively large amount being released as lipoproteins into the bloodstream so that blood cholesterol still remains high. 

Therapy - Since hypercholesterolemia and hypertension are more easily determined in the living than is the diagnosis of the atherosclerotic condition, therapy for the disease depends on diagnosis by inference in most cases. Therefore, treatment of elevated plasma cholesterol levels and elevated blood pressure by drugs and other measures is Interpreted as therapeutic measures for atherosclerosis. Indeed, many studies have been reported indicating relief of a variety of symptoms when the above two parameters have been normalized. (However, treatment of hypertension does not fall under the scope of this chapter). In hypercholesterolemia, dietary measures have been applied to both prophylactic and therapeutic purposes and include reduction of intake of cholesterol-rich foods, high-fat foods, and total caloric level. 

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