740
P A R T 8
Drugs acting on the cardiovascular system
■■
Bile acid sequestrants prevent the reabsorption
of bile salts, which are very high in cholesterol.
Consequently, the liver will pull cholesterol from the
blood to make new bile acids, lowering the serum
cholesterol level.
■■
People receiving bile acid sequestrants need to learn
how to mix the powders or, if taking the tablet form,
the importance of swallowing the tablet whole and
not cutting, crushing or chewing it. Doses should not
be taken with other drugs to avoid problems with
absorption.
■■
GI problems are often reported when using bile
acid sequestrants, including nausea, bloating and
constipation.
HMG-C
o
A
reductase
inhibitors
The HMG-CoA reductase inhibitors include atorva
statin (
Lipitor
), fluvastatin (
Lescol
), pravastatin
(
Cholstat
,
Pravachol
), rosuvastatin (
Crestor
) and sim-
vastatin (
Simvar
,
Zocor
).
Therapeutic actions and indication
The early rate-limiting step in the synthesis of cellular
cholesterol involves the enzyme HMG-CoA reductase.
If this enzyme is blocked, serum cholesterol and LDL
levels decrease because more LDLs are absorbed by the
cells for processing into cholesterol. In contrast, HDL
levels increase slightly with this alteration in fat metabo-
lism. HMG-CoA reductase inhibitors block HMG-CoA
reductase from completing the synthesis of cholesterol
(see Figure 47.2). Most of these drugs are chemical modi
fications of compounds produced by fungi. As a group,
they are frequently referred to as “statins”. Because these
drugs undergo a marked first-pass effect in the liver,
most of their effects are seen in the liver (see Adverse
effects). These drugs may also have some effects on the
KEY POINTS
process that generates atheromas in vessel walls. That
exact mechanism of action is not understood. These
drugs are indicated as adjuncts with diet and exercise
for the treatment of increased cholesterol and LDL levels
that are unresponsive to dietary restrictions alone.
Pravastatin and simvastatin are indicated for indi-
viduals with documented CAD to slow progression of
the disease. These two agents and atorvastatin are used
to prevent a first myocardial infarction (MI) in people
who have multiple risk factors for developing CAD.
Table 47.3 discusses usual indications for each of the
HMG-CoA reductase inhibitors. Several of the statin
drugs have been formulated as combination therapy.
Examples of combination therapy are highlighted in
Box 47.6.
Evaluation
■
■
Monitor response to the drug as appropriate
(reduction in serum cholesterol levels).
■
■
Monitor for adverse effects (headache, vitamin
deficiency, increased bleeding times, constipation,
nausea, rash).
■
■
Evaluate the effectiveness of the teaching plan
(person can name drug, dosage, adverse effects
to watch for and specific measures to avoid them;
person understands the importance of continued
follow-up).
■
■
Monitor the effectiveness of comfort measures and
compliance with the regimen.
In recent years, combination therapy for reducing the
risk of atherosclerosis in people with multiple risk
factors has been introduced in Australia. It has been
thought that the convenience of taking one tablet each
day would improve compliance with the lipid-lowering
therapy and other complementary medicines.
Newer combination drugs for treating CAD
•
Caduet
and
Cadatin
are combinations of 5 or 10 mg
amlodipine and 10, 20, 40 or 80 mg atorvastatin.
The person should first be stabilised on the individual
drugs before the correct combination is selected. The
combination provides the blood pressure–lowering
and antianginal effect of the amlodipine with the
lipid-lowering effects of the atorvastatin. The usual
adult dose is 5 to 10 mg amlodipine with 10 to 80 mg
atorvastatin, based on the individual’s response.
The recommended dose in children 10 to 17 years
of age is 2.5 to 5 mg amlodipine with 10 to 20 mg
atorvastatin.
•
Vytorin
, introduced in 2005, is a combination of
ezetimibe and simvastatin, and was approved to help
lower lipid levels in people who did not have good
results with single-drug therapy. Ezetimibe decreases
the absorption of cholesterol, and simvastatin
decreases the body’s production of cholesterol.
The drug is available in tablets that contain 10 mg
ezetimibe and 10, 20, 40 or 80 mg simvastatin.
Dose should be determined based on lipid levels.
The ENHANCE study reported disappointing
effectiveness of this combination.
•
Juvicor
is a combination of 100 mg sitagliptin and 10,
20 or 40 mg simvastatin. This drug is used to manage
type 2 diabetes mellitus as well as reducing serum
cholesterol levels.
Only Vytorin is available in New Zealand at time of
publication.
■■
BOX 47.6
Combination therapy for lowering
cholesterol levels
