also adsorb co-administered drugs such as digitoxin and diuretics, thereby decreasing
their bioavailability.
Another drug that is still sometimes used to inhibit cholesterol biosynthesis is
clofibrate (5.14), an isobutyrate derivative. Bezafibrate (5.15), etofibrate (5.16), and
gemfibrozil (5.17) are other bioactive analogs in this class of drugs. These agents seem
to block cholesterol synthesis at the point at which cholesterol exerts feedback inhibi-
tion on its own synthesis: at the formation of mevalonate. They also block acetyl-CoA
carboxylase, the enzyme producing malonyl-CoA. However, clofibrate is far from
being an ideal drug as it has numerous side effects. It is being largely replaced by the
statins.
Nicotinic acid (5.18), and related derivatives such as pyridylcarbinol (5.19), xanthinol
nicotinate (5.20), acipimox (5.21), given in large doses, influence the lipoprotein ratio,
decreasing the concentrations of very low and low-density lipoprotein, but have no
effect on HDL–cholesterol complexes. Acipimox (5.21) is a new pyrazine derivative
that is 20 times more active than nicotinic acid. When first administered, the use of
these agents is associated with flushing and hypotension.
Since atherosclerosis is an important cause of pathology in our aging population,
drug design will continue to focus on this challenging but fruitful area of research.
5.7 STEROID HORMONES: SEX HORMONES—INTRODUCTION
Of the various steroid hormones produced from cholesterol, the sex hormones are
extremely important. The reproductive steroid hormones are divided into three
classes:
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