C H A P T E R 4 7
Lipid-lowering agents
745
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The cholesterol absorption inhibitor ezetimibe works
in the brush border of the small intestine to prevent
the absorption of dietary cholesterol, which leads to
increased clearance of cholesterol by the liver and a
resultant fall in serum cholesterol.
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Change in diet and increased exercise are very
important parts of the overall treatment of a person
receiving a cholesterol absorption inhibitor.
O
ther
lipid
-
lowering agents
Other drugs that are used to affect lipid levels do not
fall into any of the classes discussed previously. They are
approved for use in combination with changes in diet
and exercise. They include the fibrates (derivatives of
fibric acid), the vitamin niacin and the peroxisome pro-
liferator receptor alpha activator, fenofibric acid.
Fibrates
The fibrates stimulate the breakdown of lipoproteins
from the tissues and their removal from the plasma. They
lead to a decrease in lipoprotein and triglyceride synthe-
sis and secretion. The fibrates are absorbed from the GI
tract and are metabolised in the liver and excreted in
urine. Fibrates in use today include the following agents:
• Fenofibrate (
Lipidil
) inhibits triglyceride synthesis
in the liver, resulting in reduction of LDL levels;
KEY POINTS
increases uric acid secretion; and may stimulate
triglyceride breakdown. It is used for adults with very
high triglyceride levels who are not responsive to strict
dietary measures and who are at risk for pancreatitis.
Peak effects are usually seen within 4 weeks, and the
person’s serum lipid levels should be re-evaluated at
that time.
• Gemfibrozil (
Jezil, Lipazil, Lopid
and others) inhibits
peripheral breakdown of lipids, reduces production
of triglycerides and LDLs and increases HDL
concentrations. It is associated with GI and muscle
discomfort. This drug should not be combined with
statins. There is an increased risk of rhabdomyolysis
from 3 weeks to several months after therapy if this
combination is used. If this combination cannot be
avoided, the individual should be monitored very
closely.
Vitamin B
Vitamin B
3
, known as nicotinic acid (generic), inhibits
the release of free fatty acids from adipose tissue,
increases the rate of triglyceride removal from plasma,
and generally reduces LDL and triglyceride levels and
increases HDL levels. It may also decrease the levels of
apoproteins needed to form chylomicrons. The initial
effect on lipid levels is usually seen within 5 to 7 days,
with the maximum effect occurring in 3 to 5 weeks.
Nicotinic acid is associated with intense cutaneous
flushing, nausea and abdominal pain, making its use
somewhat limited. It also increases serum levels of uric
acid and may predispose people to the development of
gout. Nicotinic acid is often combined with bile acid
sequestrants for increased effect. It is given at bedtime to
make maximum use of night time cholesterol synthesis,
and it must be given 4 to 6 hours after the bile seques-
trant to ensure absorption.
Peroxisome proliferator receptor alpha activator
In 2009, the US Food and Drug Administration (FDA)
approved the first drug in a new class of drugs called
peroxisome proliferator receptor alpha activators.
Fenofibric acid (
Trilipix
) is the first drug in this class.
This drug is not yet available in New Zealand and Aus-
tralia. It works to activate a specific hepatic receptor
that results in increased breakdown of lipids, elimina-
tion of triglyceride-rich particles from the plasma, and
reduction in the production of an enzyme that natur
ally inhibits lipid breakdown. The result is seen as a
decrease in triglyceride levels, changes in LDL produc-
tion that makes them more easily broken down in the
body, and an increase in HDL levels. Fenofibric acid is
used in combination with a statin to reduce triglycer-
ide levels and increase HDL levels in people with mixed
lipid disorders; as monotherapy to decrease triglyceride
levels in people with severe hypertriglyceridaemia; and
as monotherapy to reduce LDL, total cholesterol and
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■
Provide thorough teaching, including the name
of the drug, dosage prescribed and schedule for
administration; measures to avoid adverse effects,
warning signs of problems, and the need for
follow-up laboratory testing to monitor cholesterol
and lipid levels; dietary and lifestyle changes
for reducing the risk of CAD and increasing the
effectiveness of drug therapy; and monitoring
and evaluation
to enhance knowledge about drug
therapy and to promote compliance.
Evaluation
■
■
Monitor response to the drug (lowering of serum
cholesterol and LDL levels, lowering of sitosterol
and campesterol levels).
■
■
Monitor for adverse effects (headache, dizziness,
GI pain, muscle aches and pains, URI).
■
■
Monitor the effectiveness of comfort measures and
compliance with the regimen.
■
■
Evaluate the effectiveness of the teaching plan
(person can name drug, dosage, adverse effects
to watch for and specific measures to avoid
them; individual understands the importance of
continued follow-up).
