Cholesterol-Lowering Drugs
Quote:
>I'm interested in learning more about the comparative properties of the most
>common cholesterol-lowering {*filter*}...Lopid, Niacin and Mevacor. Aside from
>lowering cholesterol levels, do any of them lower LDL or raise HDL levels? Do
>anyof these exhibit serious side effects and, if so, what are these?
Well, in a nutshell, gemfibrozil (Lopid) is mainly used to treat elevated
triglycerides along with elevated cholesterol. It has a mild effect on
lowering LDL cholesterol. It lowers VLDL (triglycerides) and tends to raise
HDL. Lovastatin (Mevacor) is most effective at lowering LDL; triglycerides
may be lowered slightly and HDH raised slightly, though these last two effects
are not as pronounced as with gemfibrozil. Niacin has its most immediate
effect on triglyceride levels; over several weeks, LDL levels are lowered
as well. There may be a slight rise in HDL. The bile-acid-binding-resins,
colestipol (Colestid) and cholestyramine (Questran) act to prevent the
reabsorption of bile acids (which are formed from cholesterol) from the gut.
More bile acids must be synthesized, and the raw material comes from the
circulating LDL. These have a mild effect on lowering LDL levels. They often
exacerbate elevated triglyceride levels. While their efficacy is not great
in and of themselves, they work synergistically with {*filter*} like niacin and
lovastatin. Probucol (Lorelco) is an unusual compound which lowers both LDL
and HDL cholesterol (often with a greater effect on HDL). Because of this,
its status in therapy is a little uncertain. It may exert as great or greater
an effect as an anti-oxidant to reduce the production of atheroscl{*filter*}
plaques. I don't think any longitudinal studies have been performed to
look at the effects of probucol on cardiovascular mortality and morbidity.
As far as serious side-effects, the resins are generally thought to be the
safest, because they are not absorbed and they exert their actions non-
systemically. The most common side effect from these {*filter*} is constipation,
which is often ameliorated by adding fiber to the diet.
Niacin has to be taken in large doses (1 to 6 grams/day), and at such
doses, it can have a variety of side effects. Flushing is the best
known, but transient, phenomenon. Liver enzymes can be elevated, and
this occasionally progresses to outright liver dysfunction. Large
doses of niacin can also cause gastric distress. Luckily, when niacin
is combined with a resin, lower doses which are better tolerated can be
used than if it were used as the sole therapy.
Gemfibrozil is generally well tolerated. This class of {*filter*} can
increase the cholesterol content of bile, and thus facilitate the
formation of gallstones, which can have their own morbidity.
Lovastatin is a member of new family of {*filter*} known as HMGCoA-reductase
inhibitors. These inhibit cholesterol synthesis at a very early
stage. Interestingly, this is not how they directly lower serum LDL:
this early inhibition causes the development of additional LDL
receptors on cell surfaces to "capture" cholesterol from the {*filter*} to
make up for this deficit. This is also how the resins work--by
requiring additional bile acids to be synthesized, the body gets the
precursor cholesterol from the serum by stimulating the creation of
LDL receptors. Lovastatin is generally well tolerated. Muscle enzymes
are occasionally elevated (without symptoms) and there are rare cases
of outright myopathy. This last effect occurs even more frequently when
it is given with another systemic drug like gemfibrozil or niacin, so
these are combined with some caution. There was some worry that lovastatin
may contribute to the formation of cataracts: these were seen after chronic
high-dose studies in dogs. In addition, another drug, triparanol (MER-29),
which inhibited cholesterol synthesis at a much later step (desmosterol-->
cholesterol) had cataracts as a frequent side effect. There doesn't seem
to be much evidence (yet) which implicates lovastatin as a causative agent
of cataracts in humans. In fact, there are some studies which indicate that
the population which would be given such a drug is already at risk for their
development. This will be better clarified over time. Anyone worried about
this should talk to their ophthalmologist.
--
Steve Dyer
