McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 4 7 Lipid-lowering agents

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 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 Continued on following page

fluvastatin (Lescol)

20–80 mg PO, taken at bedtime; >2 hours after a bile acid sequestrant, if this combination is being used