Antihyperlipidemic: Generic and Brand Names
- Bile Acid Sequestrants
- cholestyramine (Questran)
- colesevelam (Welchol)
- colestipol (Colestid)
- HMG-CoA Reductase Inhibitors
- atorvastatin (Lipitor)
- fluvastatin (Lescol)
- lovastatin (Mevacor)
- pitavastatin (Livalo)
- pravastatin (Pravanchol)
- simvastatin (Zocor)
- Cholesterol Absorption Inhibitor
- ezetimibe (Zetia)
- Fibrates
- fenofibrate (TriCor)
- fenofibric acid (Tripilix)
- gemfibrozil (Lopid)
- Vitamin B
- niacin (Niaspan)
Disease Spotlight: Coronary Artery Disease (CAD)
Fatty streaks form in the coronary artery endothelium and over time build into plaques (atheromas) that injure the vessel lining. The inflammatory reaction draws in white blood cells and platelets, which collect on the injured vessel and grow the atheroma, narrowing the lumen and limiting blood flow. The injury makes the vessel stiffer, less distensible, and less reactive to neurochemical stimuli, so the coronary arteries can no longer balance oxygen demand against supply. Untreated, this leads to total blockage and vessel rupture. CAD is the leading cause of death worldwide and is common in people with hyperlipidemia. The cause is unknown, but risk factors include increasing age, male gender, sedentary lifestyle, smoking, obesity, high-fat diet, high stress, menopause, and conditions like hypertension, gout, and diabetes.
Bile Acid Sequestrants
These drugs normalize high serum cholesterol.
Therapeutic Action
Bile acid sequestrants work in the intestine, binding bile acids (which carry a high cholesterol load) into an insoluble complex that is excreted in feces. To replace the lost bile acids, the liver pulls more LDL from circulation, lowering serum levels.
Indications
Primary hypercholesterolemia (high cholesterol and high LDL) as an adjunct to diet and exercise. Cholestyramine also treats pruritus from partial biliary obstruction.
By age group: in children, familial hypercholesterolemia is managed with tight calorie and fat restriction because lipids matter for nervous system development; other classes are added only when diet fails. In adults, sequestrants are combined with HMG-CoA reductase inhibitors when statins alone cannot normalize lipids, and they are the drug of choice in pregnant women. In older adults, outcome data do not support lipid-lowering agents, so reinforce lifestyle changes and teach that these drugs cannot be cut, crushed, or chewed.
Pharmacokinetics
Not absorbed systemically and excreted in feces.
Contraindications and Cautions
Allergy to bile acid sequestrants. Complete biliary obstruction, which prevents bile from reaching the intestines. Abnormal intestinal function, which the drug aggravates. Pregnancy and lactation, because decreased absorption of fat and fat-soluble vitamins can harm the fetus or neonate.
Adverse Effects
CNS: headache, anxiety, fatigue, drowsiness. GI: GI upset, constipation, fecal impaction, nausea, aggravated hemorrhoids. Heme: increased bleeding time, decreased production of clotting factors. Musculoskeletal: muscle aches and pains. Other: rash, fat-soluble vitamin deficiencies.
Interactions
Bile acid sequestrants delay absorption of thiazide diuretics, corticosteroids, digoxin, warfarin, and thyroid hormones, so give those drugs 1 hour before or 4-6 hours after a meal.
Nursing Considerations
Assess for the contraindications above and do a full physical for baseline. Get baseline weight and note recent gains or losses for fluid status. Check neurological status (orientation, alertness) for CNS effects, and bowel patterns (stool frequency and characteristics) for constipation and possible fecal impaction. Watch heart rate and blood pressure for cardiovascular changes that may warrant a dose change, inspect the abdomen for distention, and auscultate bowel sounds for GI motility changes. Monitor serum cholesterol and lipid levels for effectiveness. Relevant nursing diagnoses include acute pain related to CNS and GI effects, risk for injury related to CNS effects and bleeding potential, and altered elimination related to constipation.
Mix powdered agents with fluid before giving them. Tell the patient not to chew, crush, or cut tablets, which are meant to break down in the intestine; premature crushing inactivates them. Give the drug before meals so it is in the GI tract with food, and give other drugs 1 hour before or 4-6 hours after the sequestrant to avoid interactions. Set up a bowel program and push oral fluids and dietary fiber to prevent constipation. Provide comfort measures (small frequent meals for GI upset, safety measures for drowsiness and weakness). Teach the drug name, indication, and adverse effects to promote adherence. Evaluate by tracking serum lipid and cholesterol levels, watching for adverse effects (headache, vitamin deficiency, increased bleeding times), confirming understanding, and monitoring compliance.
HMG-CoA Reductase Inhibitors
This group (the statins) increases cell absorption of LDL by blocking HMG-CoA reductase, the enzyme controlling the rate-limiting step of cholesterol synthesis. With fat metabolism altered, HDL rises slightly. These drugs are chemically modified compounds derived from fungi.
Therapeutic Action
Statins block the completion of cholesterol synthesis in the body. They are indicated mainly as an adjunct to diet and exercise for high cholesterol and LDL.
Indications
Pravastatin, lovastatin, and simvastatin slow disease progression in patients with documented CAD. Along with those three, atorvastatin is used as prophylaxis against a first myocardial infarction in patients with multiple CAD risk factors.
By age group: in children, familial hypercholesterolemia is strictly limited to tight fat and calorie restriction because lipids matter for nervous system development. In adults, statins are the drug of choice for patients with multiple risk factors or established CAD; emphasize lifestyle changes (diet, exercise, smoking cessation). This class is well tolerated and cheaper than others with the same effect; for slow responders, combine with niacin, a fibrate, or a bile acid sequestrant. In July 2021 the FDA removed its strongest warning (the blanket contraindication) against statin use in pregnancy, but it still advises that most pregnant patients stop statins, with continuation reserved for individualized decisions in very high-risk patients such as those with homozygous familial hypercholesterolemia or prior cardiovascular events; patients should not breastfeed while taking a statin (FDA). Older adults are more prone to drug toxicity from underlying conditions that interfere with metabolism and excretion, so reinforce lifestyle changes.
Pharmacokinetics
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Oral | Slow | 1-2 h | 20-30 h |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 14 h | liver | bile |
Contraindications and Cautions
Allergy to HMG-CoA reductase inhibitors. Active liver disease, which the drug's effect can worsen toward severe liver failure. Pregnancy and lactation, for potential adverse effects on the fetus or neonate. Impaired endocrine function, because of altered steroid hormone formation. Renal impairment, which calls for caution and close monitoring with most statins, though atorvastatin is not affected by renal disease.
Adverse Effects
CNS: headache, dizziness, insomnia, fatigue, blurred vision, cataract development. CV: increased cardiovascular risk with simvastatin started at 80 mg in new patients. GI: flatulence, nausea, vomiting, cramps, abdominal pain, constipation. Hepatobiliary: increased liver enzymes, acute liver failure with atorvastatin and fluvastatin.
Interactions
Cyclosporine, erythromycin, gemfibrozil, niacin, and antifungals increase the risk of rhabdomyolysis. Digoxin and warfarin increase statin serum levels and toxicity. Oral contraceptives raise serum estrogen. Grapefruit juice increases serum levels and toxicity.
Nursing Considerations
Assess for the contraindications above (hypersensitivity, acute liver disease, pregnancy) and do a full physical for baseline. Get baseline weight and note recent changes for fluid status. Check neurological status (consciousness, reflexes, affect), heart rate and blood pressure for cardiovascular changes that may warrant a dose change, and bowel patterns for constipation and possible fecal impaction. Relevant nursing diagnoses include disturbed sensory perception and risk for injury related to CNS effects.
Give the drug at bedtime, since cholesterol synthesis peaks from midnight to 5 AM; atorvastatin can be given at any hour. Monitor serum cholesterol and LDL for effectiveness and liver function tests for damage. Confirm the patient has tried a 3-6 month diet and exercise program before starting the drug. Emphasize lifestyle changes to cut CAD risk, provide comfort and safety measures, and teach the drug name, indication, and adverse effects. Evaluate by tracking normal cholesterol and LDL, absence of a first MI, and slowed CAD progression, watching for adverse effects (cataracts, rhabdomyolysis, acute liver disease), confirming understanding, and monitoring compliance.
Cholesterol Absorption Inhibitors
Cholesterol absorption inhibitors (ezetimibe) are a class approved in 2002 to lower serum cholesterol. An early imaging study (ENHANCE, 2008) showed no benefit from adding ezetimibe to a statin, which fueled debate, but the larger IMPROVE-IT trial (2015) later found that adding ezetimibe to a statin after acute coronary syndrome modestly reduced cardiovascular events compared with the statin alone, supporting its use as add-on therapy when statins do not get LDL low enough (IMPROVE-IT).
Therapeutic Action
Acting on the intestinal brush border, these drugs block absorption of dietary cholesterol. Less cholesterol reaches the liver, which increases cholesterol clearance to compensate.
Indications
Adjunct to diet and exercise, as monotherapy or combined with HMG-CoA inhibitors or bile acid sequestrants, and combined with statins to treat homozygous familial hypercholesterolemia.
By age group: not indicated in children. In adults, used with HMG-CoA inhibitors or bile acid sequestrants alongside emphasized lifestyle changes; effects on the fetus and neonate are unknown. Older adults are more prone to toxicity from conditions interfering with metabolism and excretion, so reinforce lifestyle changes.
Pharmacokinetics
| Route | Onset | Peak |
|---|---|---|
| Oral | Moderate | 4-12 h |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 22 h | liver, small intestine | urine, feces |
Contraindications and Cautions
Allergy to cholesterol absorption inhibitors. Liver disease, pregnancy, and lactation: not used combined with statins because of statins' effects in these conditions, and effects on the fetus and neonate are unknown.
Adverse Effects
CNS: headache, dizziness, fatigue. Respiratory: upper respiratory tract infection. GI: mild abdominal pain, diarrhea. Musculoskeletal: muscle aches and pains, back pain.
Interactions
Cholestyramine, fenofibrate, antacids, and gemfibrozil elevate serum levels of cholesterol absorption inhibitors. Cyclosporine increases their toxicity. Fibrates increase the risk of cholelithiasis. Warfarin levels rise.
Nursing Considerations
Assess for the contraindications above (hypersensitivity, acute liver disease, pregnancy) and do a full physical for baseline. Check neurological status (orientation, reflexes) for CNS effects, heart rate and blood pressure for cardiovascular changes, and bowel patterns for constipation and possible fecal impaction. Monitor serum cholesterol, LDL, and liver function for adverse effects and effectiveness. Relevant nursing diagnoses include disturbed sensory perception, acute pain (headache, myalgia, GI distress), and risk for injury related to CNS effects.
Monitor serum cholesterol and LDL for effectiveness and liver function tests for damage. Confirm a 3-6 month diet and exercise program before starting the drug. Emphasize lifestyle changes to cut CAD risk, provide comfort and safety measures, and teach the drug name, indication, and adverse effects. Evaluate by tracking normal cholesterol and LDL, watching for adverse effects (muscle pains, respiratory infections, headache), confirming understanding, and monitoring compliance.
Frequently Asked Questions
Why are statins taken at bedtime?
Cholesterol synthesis peaks overnight, roughly midnight to 5 AM, so most statins work best when dosed at bedtime. The longer-acting agents (atorvastatin and rosuvastatin) are the exception and can be taken at any time of day.
What is the most important muscle-related side effect of statins?
Muscle aches are common, but the concern is rhabdomyolysis, a breakdown of muscle that can injure the kidneys. Risk rises when statins are combined with drugs such as cyclosporine, gemfibrozil, certain antifungals, erythromycin, or niacin, so teach patients to report unexplained muscle pain, tenderness, or dark urine.
Can statins be used during pregnancy?
In July 2021 the FDA removed its strongest warning against statin use in pregnancy, but it still advises that most pregnant patients stop statins. Continuation is an individualized decision for very high-risk patients, and patients should not breastfeed while taking a statin (FDA).
Does adding ezetimibe to a statin actually help?
An early imaging study (ENHANCE, 2008) showed no benefit, but the larger IMPROVE-IT trial (2015) found that adding ezetimibe to a statin after acute coronary syndrome modestly lowered cardiovascular events versus the statin alone. It is a reasonable add-on when a statin alone does not bring LDL low enough (IMPROVE-IT).
Why must bile acid sequestrants be separated from other drugs?
They bind drugs in the gut and delay absorption of agents like thiazide diuretics, corticosteroids, digoxin, warfarin, and thyroid hormones. Give other medications 1 hour before or 4 to 6 hours after the sequestrant, and never crush or chew the tablets, which are meant to break down in the intestine.
Should patients on statins avoid grapefruit juice?
Grapefruit juice inhibits the enzyme that clears several statins (notably simvastatin and lovastatin), raising blood levels and the risk of muscle toxicity. Patients on those statins should avoid grapefruit juice; pravastatin and rosuvastatin are less affected.