Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Introduction to Clinical
Pharmacology
Chapter 35-
A...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Lipoproteins
• Low-density lipoproteins (LDL):
– Tr...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Cholesterol Levels
• HDL cholesterol: Protects agai...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
HMG-CoA Reductase Inhibitors: Actions
• HMG-CoA red...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
HMG-CoA Reductase Inhibitors: Uses
• As adjunct to ...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
HMG-CoA Reductase Inhibitors: Adverse
Reactions
• C...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
HMG-CoA Reductase Inhibitors:
Contraindications And...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
HMG-CoA Reductase Inhibitors:
Interactions
Interact...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
HMG-CoA Reductase Inhibitors:
Interactions (cont’d)...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Bile Acid Sequestrants: Actions and Use
• Bile: Man...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Bile Acid Sequestrants: Adverse
Reactions
• Constip...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Bile Acid Sequestrants: Contraindications
And Preca...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Bile Acid Sequestrants : Interactions
Drug Interact...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Bile Acid Sequestrants : Interactions
(cont’d)
Drug...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Fibric Acid Derivatives: Actions
• Clofibrate:
– St...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Fibric Acid Derivatives: Actions (cont’d)
• Gemfibr...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Fibric Acid Derivatives: Uses
• Clofibrate and gemf...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Fibric Acid Derivatives
• Adverse Reactions:
– Naus...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Fibric Acid Derivatives: Interactions
Interactant D...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Fibric Acid Derivatives: Interactions
(cont’d)
Inte...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Miscellaneous Antihyperlipidemic Drugs:
Niacin
• Ac...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Miscellaneous Antihyperlipidemic Drugs:
Contraindic...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Nursing Process: Assessment
• Preadministration ass...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Nursing Process: Planning
• Expected outcome:
– Opt...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Nursing Process: Implementation
• Promoting an opti...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Nursing Process: Implementation
• Monitoring and ma...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Nursing Process: Implementation
• Monitoring and ma...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Nursing Process: Implementation
• Monitoring and ma...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Nursing Process: Implementation
• Educating the pat...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Nursing Process: Evaluation
• Therapeutic effect is...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Nursing Process: Evaluation (cont’d)
• Skin will re...
Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
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  1. 1. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Introduction to Clinical Pharmacology Chapter 35- Antihyperlipidemic Drugs
  2. 2. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Lipoproteins • Low-density lipoproteins (LDL): – Transport cholesterol to the peripheral cells – Elevation of LDL: •Atherosclerotic plaque formation •Increases the risk for heart disease • High-density lipoproteins (HDL): – Take cholesterol from the peripheral cells and transport it to the liver
  3. 3. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Cholesterol Levels • HDL cholesterol: Protects against heart diseases • Higher the LDL level: Greater the risk for heart disease • Drugs used to treat hyperlipidemia: – Bile acid sequestrants – HMG-CoA reductase inhibitors – Fibric acid derivatives – Niacin
  4. 4. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins HMG-CoA Reductase Inhibitors: Actions • HMG-CoA reductase: – An enzyme that is a catalyst during the manufacture of cholesterol • Inhibits the manufacture of cholesterol or promotes the breakdown of cholesterol • Lowers the blood levels of cholesterol and serum triglycerides • Increases blood levels of HDLs
  5. 5. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins HMG-CoA Reductase Inhibitors: Uses • As adjunct to diet in the treatment of hyperlipidemia • For primary prevention of coronary events • For secondary prevention of cardiovascular events
  6. 6. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins HMG-CoA Reductase Inhibitors: Adverse Reactions • Central nervous system reactions: – Headache, blurred vision, dizziness, insomnia • Gastrointestinal reactions: – Flatulence, abdominal pain, cramping, constipation, nausea • Other: – Elevated CPK level, Rhabdomyolysis with possible renal failure
  7. 7. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins HMG-CoA Reductase Inhibitors: Contraindications And Precautions • Contraindicated in patients: – With hypersensitivity to the drugs, serious liver disorders – During pregnancy and lactation • Used cautiously in patients with: – History of alcoholism, acute infection, hypotension, trauma, endocrine disorders, visual disturbances, and myopathy
  8. 8. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins HMG-CoA Reductase Inhibitors: Interactions Interactant Drug Effect of Interaction Macrolides, erythromycin, clarithromycin Increased risk of severe myopathy or rhabdomyolysis Amiodarone Increased risk for myopathy and for severe myopathy or rhabdomyolysis Niacin Increased risk for severe myopathy or rhabdomyolysis
  9. 9. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins HMG-CoA Reductase Inhibitors: Interactions (cont’d) Interactant Drug Effect of Interaction Protease inhibitors Elevated plasma levels of HMG-CoA reductase inhibitors Verapamil Increased risk for myopathy Warfarin Increased anticoagulant effect
  10. 10. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Bile Acid Sequestrants: Actions and Use • Bile: Manufactured, secreted by liver – Stored in the gallbladder, emulsifies fat, lipids • Increased loss of bile acids: – Liver uses cholesterol to manufacture more bile • Used to treat: Hyperlipidemia; Pruritus associated with partial biliary obstruction
  11. 11. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Bile Acid Sequestrants: Adverse Reactions • Constipation • Aggravation of hemorrhoids • Abdominal cramps • Flatulence • Nausea • Increased bleeding tendencies related to vitamin K malabsorption, and vitamin A and D deficiencies
  12. 12. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Bile Acid Sequestrants: Contraindications And Precautions • Contraindicated in patients : – With known hypersensitivity to the drugs – With complete biliary obstruction • Used cautiously in patients: – With liver disease, kidney disease – During pregnancy and lactation
  13. 13. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Bile Acid Sequestrants : Interactions Drug Interactant Effect of Interaction Anticoagulants Decreased effect of the anticoagulant (cholestyramine) Thyroid hormone Loss of efficacy of thyroid; also hypothyroidism (particularly with cholestyramine) Ursodiol Reduced absorption of ursodiol (particularly cholestyramine and colestipol)
  14. 14. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Bile Acid Sequestrants : Interactions (cont’d) Drug Interactant Effect of Interaction Aspirin, clindamycin, penicillin G, tetracycline, clofibrate, niacin, digitalis glycosides, Decreased serum level or decreased GI absorption Furosemide, thiazide diuretics, hydrocortisone, methyldopa propranolol, phenytoin Decreased serum level or decreased GI absorption
  15. 15. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Fibric Acid Derivatives: Actions • Clofibrate: – Stimulates liver to increase breakdown of very–low-density lipoproteins (VLDLs) to low-density lipoproteins (LDLs); Decreases liver synthesis of VLDLs and inhibites cholesterol formation • Fenofibrate: – Reduces VLDL; Stimulates catabolism of triglyceride-rich lipoproteins; Decreases plasma triglyceride, cholesterol
  16. 16. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Fibric Acid Derivatives: Actions (cont’d) • Gemfibrozil: – Increases excretion of cholesterol in the feces – Reduces the production of triglycerides by the liver – Lowers serum lipid levels
  17. 17. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Fibric Acid Derivatives: Uses • Clofibrate and gemfibrozil: – Used to treat individuals with very high serum triglyceride levels who are at risk for abdominal pain, pancreatitis • Fenofibrate: – Used as adjunctive treatment for reducing LDL, total cholesterol, triglycerides in patients with hyperlipidemia
  18. 18. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Fibric Acid Derivatives • Adverse Reactions: – Nausea, vomiting, GI upset, diarrhea, cholelithiasis or cholecystitis • Contraindicated in patients: – With hypersensitivity to the drugs and those with significant hepatic or renal dysfunction or primary biliary cirrhosis • Used cautiously in patients with: – Peptic ulcer disease, diabetes, during pregnancy and lactation
  19. 19. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Fibric Acid Derivatives: Interactions Interactant Drug Effect of Interaction Anticoagulants Enhanced effects of the anticoagulants (particularly with gemfibrozil and fenofibrate) Cyclosporine Decreased effects of cyclosporine (particularly with gemfibrozil)
  20. 20. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Fibric Acid Derivatives: Interactions (cont’d) Interactant Drug Effect of Interaction HMG-CoA Increased risk for rhabdomyolysis (particularly with gemfibrozil and fenofibrate) Sulfonylureas Increased hypoglycemic effects (particularly with gemfibrozil)
  21. 21. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Miscellaneous Antihyperlipidemic Drugs: Niacin • Action: Lowers blood lipid levels • Uses: Adjunctive therapy for lowering very high serum triglyceride levels in patients who are at risk for pancreatitis • Adverse reactions: – Gastrointestinal reactions: Nausea, vomiting, abdominal pain, diarrhea – Other reactions: Severe generalized flushing of the skin, sensation of warmth, severe itching or tingling
  22. 22. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Miscellaneous Antihyperlipidemic Drugs: Contraindications And Precautions • Contraindicated in patients: – With known hypersensitivity to niacin, active peptic ulcer, hepatic dysfunction, and arterial bleeding • Used cautiously in patients with: – Renal dysfunction, high alcohol consumption, unstable angina, gout, pregnancy
  23. 23. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Nursing Process: Assessment • Preadministration assessment: – Take a dietary history; Record vital signs and weight; Inspect skin and eyelids for evidence of xanthomas • Ongoing assessment: – Monitor liver function tests, such as serum transaminase levels – Frequently monitor blood cholesterol and triglyceride levels – Periodic lipid profiles
  24. 24. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Nursing Process: Planning • Expected outcome: – Optimal response to therapy – Management of common adverse drug reactions – Understanding of the dietary measures necessary to reduce lipid and lipoprotein levels
  25. 25. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Nursing Process: Implementation • Promoting an optimal response to therapy: – Explain drug regimen and possible adverse reactions – Emphasize the importance of following printed dietary guidelines
  26. 26. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Nursing Process: Implementation • Monitoring and managing patient needs: – Constipation: Increase fluid intake, eat foods high in dietary fiber, exercise daily – Risk for imbalanced nutrition: Less Than Body Requirements • Bile acid sequestrants used for long- term therapy: Administer vitamins A, D in water-soluble form or parenterally
  27. 27. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Nursing Process: Implementation • Monitoring and managing patient needs (cont’d): – Risk for impaired skin integrity: Contact health care provider – Nausea: Take drug with meal; Provide patient with several small meals rather than three large meals – Risk for injury: Place the call light within easy reach
  28. 28. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Nursing Process: Implementation • Monitoring and managing patient needs (cont’d): – Potential complication: •Vitamin k deficiency: Include foods high in vitamin k in the patient’s diet •Rhabdomyolysis: Be alert for unexplained muscle pain, muscle tenderness, or weakness, especially if accompanied by malaise or fever
  29. 29. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Nursing Process: Implementation • Educating the patient and family: – Provide and review the recommended diet with the patient and family – Explain the importance of taking the drug at prescribed time intervals and as directed – Explain the necessity of contacting the primary health care provider immediately if symptoms occur
  30. 30. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Nursing Process: Evaluation • Therapeutic effect is achieved; Serum lipid levels are decreased • Adverse reactions are identified, reported, and managed successfully • Improved bowel movements • Nutritional vitamin needs will be met
  31. 31. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins Nursing Process: Evaluation (cont’d) • Skin will remain intact • Nausea is controlled • The patient reports no injury related to dizziness or falls • The patient and family demonstrate understanding of the treatment regimen
  32. 32. Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins End of Presentation
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