Ppt chapter 28

Chapter 28
Drugs Affecting Lipid Levels
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Question
• What is the optimal low-density lipoprotein (LDL) level?
– A. 200 mg/dL
– B. 160 mg/dL
– C. 130 mg/dL
– D. 100 mg/dL

Answer
• D. 100 mg/dL
• Rationale: 100 mg/dL is the optimal LDL level
according to NCEP. Some newer data are suggesting that
the LDL should be even lower than that in patients with
risk factors for myocardial infarctions and strokes.

Physiology
• Serum lipids are fats found in the bloodstream.
• These lipids include cholesterol, cholesterol esters
(compounds), phospholipids, and triglycerides.
• They are transported in the blood as part of large
molecules called lipoproteins.
• Cholesterol is a soft, waxy substance found among the
lipids in the bloodstream and in all of the body’s cells.

Physiology (cont.)
• The body, mostly in the liver, produces essentially all of
the cholesterol needed for normal functioning—about
1,000 mg a day.
• Cholesterol plays a role in forming cell membranes, some
hormones, and other needed tissues.
• LDL is the major cholesterol carrier in the blood.

Pathophysiology
• Hyperlipidemia is an elevation of blood lipid levels.
• Hyperlipidemia is considered a risk factor for the
following disorders: atherosclerosis, coronary artery
disease, and thromboses.
• When the amount of cholesterol within cells builds up,
the number of these receptors on cell surfaces is
reduced, preventing all of the lipids from entering the
cells.

Pathophysiology (cont.)
• Patients with narrowed arteries from atherosclerotic
cardiovascular disease are more likely to have
hypertension.
• Ideal cholesterol levels:
– Total cholesterol: less than 200 mg/dL
– LDL: 100 mg/dL
– HDL: 40 to 59 mg/dL

Lifestyle and Reduction of Low-Density
Lipoprotein Levels
• The NCEP ATP III recommends a multipronged approach
in reducing LDL levels.
• They title this approach therapeutic lifestyle changes.
• These lifestyle changes include:
– Diet
– Weight loss
– Increased physical activity

Antihyperlipidemics

Statins
• Statins lower blood cholesterol levels and thus decrease
the uptake of modified lipoproteins by vascular cells.
• Statin therapy can lower LDL cholesterol by 20% to 55%
when given at their maximum recommended dose.
• Statins also raise HDL levels between 5% and 15% and
lower triglycerides between 7% and 33%.
• In addition, evidence exists that statins work in other
ways beside lowering cholesterol levels to decrease the
occurrence of cardiovascular events.
• Prototype drug: lovastatin (Mevacor)

Lovastatin: Core Drug Knowledge
• Pharmacotherapeutics
– Used for primary hypercholesterolemia and combined
hyperlipidemia
• Pharmacokinetics
– High first-pass effect. Highly protein bound. Excreted
primarily through the GI tract
• Pharmacodynamics
– Competitively inhibits HMG-CoA reductase, which is
the enzyme that catalyzes the early rate-limiting step
in cholesterol biosynthesis

Lovastatin: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Active liver disease and pregnancy
• Adverse effects
– Muscle and joint aches, weakness, cramps, muscle
damage, liver damage, and rhabdomyolysis
• Drug interactions
– Itraconazole, erythromycin, and grapefruit juice

Lovastatin: Core Patient Variables
• Health status
– Assess cholesterol levels and past medical history.
• Life span and gender
– Pregnancy category X; assess age of the patient
• Lifestyle, diet, and habits
– Treat elevated cholesterol with diet and exercise first.
• Environment
– Assess environment where drug will be given.
• Culture and inherited traits
– Explore cultural dietary practices.

Lovastatin: Nursing Diagnoses and
Outcomes
• Risk for Injury related to elevated blood lipid levels
– Desired outcome: The patient’s blood lipid levels
will be controlled without the patient’s sustaining an
injury.
• Risk for Injury to skeletal muscles related to adverse
effects of drug therapy
– Desired outcome: The patient will not incur serious
skeletal muscle injury while on drug therapy.

Lovastatin: Nursing Diagnoses and
Outcomes (cont.)
• Risk for Injury to liver function related to adverse effects
of drug therapy
– Desired outcome: The patient will not incur serious
liver injury while on drug therapy.
• Risk for Altered Nutrition: Less than Body Requirements
related to adverse effects of drug therapy
– Desired outcome: The patient will not have GI
adverse effects serious enough to alter meeting the
body’s nutritional needs.

Lovastatin: Planning and Interventions
• Maximizing therapeutic effects
– Most effective when administered in the evening
– Immediate-release administered after evening meal
– Extended-release administered at bedtime
• Minimizing adverse effects
– Liver function test (AST and ALT) results should be
monitored before starting therapy.
– Evaluate the patient carefully for muscle soreness,
tenderness, or pain and CK levels.

Lovastatin: Teaching, Assessment, and
Evaluations
• Patient and family education
– Stress the importance of following a low-cholesterol
and low-saturated-fat diet.
– Instruct patients to report any unexplained muscle
pain, tenderness, or weakness.
– Photosensitivity may occur.
• Ongoing assessment and evaluation
– The patient should have liver function tests and CK
measurement performed periodically throughout
drug therapy.

Question
• Lovastatin is metabolized by which of the following
process/system?
– A. CYP3A4
– B. 2D6
– C. C121
– D. No process is needed for metabolism.

Answer
• A. CYP3A4
• Rationale: Lovastatin is metabolism by CYP3A4.

Drugs Closely Related to Lovastatin
• Atorvastatin (Lipitor), fluvastatin (Lescol), pravastatin
(Pravachol), rosuvastatin (Crestor), and simvastatin
(Zocor)
• All work similarly to lower LDL cholesterol and have
similar adverse effects.
• Pravastatin differs from the prototype lovastatin because
it is not metabolized via the P-450 system and thus does
not produce the drug interactions of lovastatin.
• Fluvastatin is primarily metabolized via a different
isoenzyme pathway.

Statin Therapy

Drugs Significantly Different from
Lovastatin: Fibric Acid Derivatives
• These drugs lower triglyceride levels and increase HDL
cholesterol.
• These drugs can reduce triglyceride levels between 35%
and 53%.
• Effects on LDL cholesterol may be either to lower it
between 6% and 20% or to raise it slightly.
• Although in certain patients these drugs may be used
alone, most frequently they are used in combination with
statins.

Lovastatin: Fibric Acid Derivatives (cont.)
• The combined used of a fibrate and a moderate-dose statin
carries a somewhat increased risk of myopathy.
• Contraindications include hepatic or severe renal
dysfunction, including primary biliary cirrhosis, preexisting
gallbladder disease, or hypersensitivity.
• Serious adverse effects include abnormal liver function
tests, rhabdomyolysis, and hyperglycemia.

Lovastatin: Cholesterol Absorption
Inhibitors
• Ezetimibe (Zetia) is an antilipid drug that is used to treat
hypercholesterolemia.
• Its pediatric use is restricted to children older than 10
years of age with familial homozygous
hypercholesterolemia.
• It is given orally once daily either as monotherapy or in
combination therapy with a statin.
• It localizes and appears to act at the brush border of the
small intestine, where it inhibits the absorption of
cholesterol.
• Ezetimibe decreases LDL about 17% but has no effect on
HDL or triglycerides.

Lovastatin: Nicotinic Acid
• Nicotinic acid (niacin or vitamin B3) is used to treat
hyperlipidemia.
• Nicotinic acid reduces levels of triglycerides and LDL
cholesterol levels and raises levels of HDL cholesterol.
• Triglycerides and VLDL levels are reduced by 25% to 30%
in 1 to 4 days. LDL level reductions may be seen in 5 to 7
days, with the maximal effect seen in 3 to 5 weeks.

Lovastatin: Nicotinic Acid (cont.)
• Contraindications to its use include hepatic dysfunction,
active peptic ulcer, severe hypotension, and
hemorrhaging.
• The newer sustained-release forms of nicotinic acid have
fewer adverse effects.
• These larger doses produce peripheral vasodilation,
mostly in the cutaneous vessels of the face, neck, and
chest.

Lovastatin: Bile Acid Sequestrants
• The bile acid sequestrants cholestyramine (LoCholest,
Questran, Prevalite) and colestipol (Colestid) are used to
reduce elevated serum cholesterol levels in patients with
primary hypercholesterolemia who have not responded to
other drug therapy.
• Bile acid sequestrants are not absorbed orally but work in
the GI tract.
• The reduction in LDLs is apparent in 4 to 7 days and
ranges between 15% and 30%.
• Bile acid sequestrants promote the oxidation of
cholesterol to bile acids.

Ppt chapter 28

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Ppt chapter 28