C H A P T E R 4 7
Lipid-lowering agents
737
of cholesterol. As a result, the liver must use cholesterol
to make more bile acids. The hepatic intracellular cho-
lesterol level falls, leading to an increased absorption of
cholesterol-containing LDL segments from circulation to
replenish the cell’s cholesterol. The serum levels of cho-
lesterol and LDL decrease as the circulating cholesterol
is used to provide the cholesterol that the liver needs to
make bile acids. These drugs are used to reduce serum
cholesterol in individuals with primary hypercholestero-
laemia (manifested by high cholesterol and high LDLs)
as an adjunct to diet and exercise. Cholestyramine is
also used to treat pruritus associated with partial biliary
obstruction
.
See Table 47.3 for usual indications for
each of these drugs.
Pharmacokinetics
Bile acid sequestrants are not absorbed systemically.
They act while in the intestine and are excreted directly
in the faeces. Their action is limited to their effects while
they are present in the intestine. Cholestyramine is a
powder that must be mixed with liquids and taken up
to six times a day. Colestipol is available in both powder
and tablet form and is taken only four times a day.
Contraindications and cautions
Bile acid sequestrants are contraindicated in the
presence of allergy to any bile acid sequestrant
to
prevent hypersensitivity reactions
. These drugs also are
contraindicated in the following conditions: complete
biliary obstruction,
which would prevent bile from
being secreted into the intestine
; abnormal intestinal
function,
which could be aggravated by the presence
of these drugs
; and pregnancy or breastfeeding
because
the potential decrease in the absorption of fat and fat-
soluble vitamins could have a detrimental effect on
the fetus or neonate.
If a lipid-lowering drug is needed,
however, a bile acid sequestrant is the drug of choice.
Adverse effects
Adverse effects associated with the use of these drugs
include headache, anxiety, fatigue and drowsiness, which
could be related to changes in serum cholesterol levels.
Direct gastrointestinal (GI) irritation, including nausea,
constipation that may progress to faecal impaction, and
aggravation of haemorrhoids may occur. Other effects
include increased bleeding times related to a decreased
absorption of vitamin K and consequent decreased pro-
duction of clotting factors; vitamin A and D deficiencies
related to decreased absorption of fat-soluble vitamins;
rash; and muscle aches and pains
.
Clinically important drug–drug interactions
Malabsorption of fat-soluble vitamins occurs when they
are combined with these drugs. These drugs decrease
or delay the absorption of thiazide diuretics, digoxin,
warfarin, thyroid hormones and corticosteroids. Con-
sequently, any of these drugs should be taken 1 hour
before or 4 to 6 hours after the bile acid sequestrant.
TABLE 47.3
DRUGS IN FOCUS Lipid-lowering drugs
Drug name
Dosage/route
Usual indications
Bile acid sequestrants
cholestyramine
(Questran)
4 g PO one to two times per day, maximum
dose 24 g/day; must be mixed with water or
other non-carbonated fluids
Adjunctive treatment of primary
hypercholesterolaemia; treatment of
pruritus associated with partial biliary
obstruction
colestipol (Colestid)
15–30 g/day PO in 2–4 divided doses
Must be mixed with 100–150 mL fluid
Adjunctive treatment of primary
hypercholesterolaemia
HMG-CoA reductase inhibitors
atorvastatin (Lipitor)
10 mg/day PO with a possible dose range of
10–80 mg/day; may be taken at any time
of day
Children (10–17 years): 10 mg/day PO,
maximum dose 20 mg/day
Adjunctive therapy for reduction of
increased cholesterol and low-density
lipoprotein (LDL) levels, triglycerides;
prevention of coronary artery disease
(CAD) in adults with multiple risk
factors; approved to lower cholesterol
levels in children 10–17 years of age
who meet specific criteria with genetic
hyperlipidaemias
fluvastatin (Lescol)
20–80 mg PO, taken at bedtime; >2 hours
after a bile acid sequestrant, if this
combination is being used
Adjunctive therapy for reduction of
increased cholesterol and LDL levels; to
slow the progression of CAD in people
with known CAD; reduction of the risk of
undergoing revascularisation procedures
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