Roach: Introductory Clinical Pharmacology

Roach: Introductory Clinical Pharmacology

Introduction to Clinical Pharmacology Chapter 34 Antihyperlipidemic Drugs Copyright 2018 Wolters Kluwer All Rights Reserved Lipoproteins Low-density lipoproteins (LDLs): Transport cholesterol to the peripheral cells Elevation of LDLs: Atherosclerotic plaque formation Increases the risk for heart disease High-density lipoproteins (HDLs):

Take cholesterol from the peripheral cells and transport it to the liver Copyright 2018 Wolters Kluwer All Rights Reserved Cholesterol Levels HDL cholesterol: protects against heart disease The higher the LDL level, the greater the risk for heart disease Drugs used to treat hyperlipidemia: Bile acid resins HMG-CoA reductase inhibitors Fibric acid derivatives Niacin

Copyright 2018 Wolters Kluwer All Rights Reserved 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 Copyright 2018 Wolters Kluwer All Rights Reserved

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 Copyright 2018 Wolters Kluwer All Rights Reserved HMG-CoA Reductase Inhibitors: Adverse Reactions Central nervous system reactions: headache, dizziness, insomnia, memory and cognitive impairment Gastrointestinal reactions: flatulence, abdominal

pain, cramping, constipation, nausea, hyperglycemia in nondiabetic patients Other: elevated CPK level, rhabdomyolysis with possible renal failure Copyright 2018 Wolters Kluwer All Rights Reserved 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, non-alcohol-related liver

disease, acute infection, hypotension, trauma, endocrine disorders, visual disturbances, and myopathy Copyright 2018 Wolters Kluwer All Rights Reserved HMG-CoA Reductase Inhibitors: Interactions #1 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 Copyright 2018 Wolters Kluwer All Rights Reserved HMG-CoA Reductase Inhibitors: Interactions #2 Interactant drug Effect of interaction Protease inhibitors Elevated plasma levels

of HMG-CoA reductase inhibitors Verapamil Increased risk for myopathy Warfarin Increased anticoagulant effect Copyright 2018 Wolters Kluwer All Rights Reserved

Bile Acid Resins: Actions and Uses 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, gallstone dissolution Copyright 2018 Wolters Kluwer All Rights Reserved Bile Acid Resins: Adverse Reactions Constipation Aggravation of hemorrhoids

Abdominal cramps Flatulence Nausea Increased bleeding tendencies related to vitamin K malabsorption, and vitamin A and D deficiencies Copyright 2018 Wolters Kluwer All Rights Reserved Bile Acid Resins: Contraindications and Precautions Contraindicated in patients: With known hypersensitivity to the drugs With complete biliary obstruction Used cautiously in patients:

With diabetes, liver disease, kidney disease, peptic ulcer During pregnancy and lactation Copyright 2018 Wolters Kluwer All Rights Reserved Bile Acid Resins: Interactions #1 Interactant drug Effect of interaction Anticoagulants Decreased effect of the

anticoagulant (cholestyramine) Thyroid hormone Loss of efficacy of thyroid; also hypothyroidism (particularly with cholestyramine) fat-soluble vitamins Reduced absorption of vitamins (A, D, E, K) and folic acid Copyright 2018 Wolters Kluwer All Rights Reserved

Bile Acid Resins : Interactions #2 Interactant drug Effect of interaction NSAIDS, penicillin G, tetracycline, glipizide, niacin, digitalis glycosides Decreased serum level or decreased GI absorption Furosemide, thiazide diuretics, hydrocortisone,

methyldopa, propranolol Decreased serum level or decreased GI absorption Copyright 2018 Wolters Kluwer All Rights Reserved Fibric Acid Derivatives: Actions #1 Fenofibrate: Reduces VLDLs Stimulates catabolism of triglyceride-rich lipoproteins Decreases plasma triglycerides, cholesterol

Copyright 2018 Wolters Kluwer All Rights Reserved Fibric Acid Derivatives: Actions #2 Gemfibrozil: Increases excretion of cholesterol in the feces Reduces the production of triglycerides by the liver Lowers serum lipid levels Copyright 2018 Wolters Kluwer All Rights Reserved Fibric Acid Derivatives: Uses 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 LDLs, total cholesterol, triglycerides in patients with hyperlipidemia Copyright 2018 Wolters Kluwer All Rights Reserved 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 Copyright 2018 Wolters Kluwer All Rights Reserved Fibric Acid Derivatives: Interactions #1 Interactant drug Effect of interaction

Anticoagulants Enhanced effects of the anticoagulants (particularly with gemfibrozil and fenofibrate) Cyclosporine Decreased effects of cyclosporine (particularly with gemfibrozil)

Copyright 2018 Wolters Kluwer All Rights Reserved Fibric Acid Derivatives: Interactions #2 Interactant drug Effect of interaction HMG-CoA Increased risk for rhabdomyolysis (particularly with gemfibrozil and fenofibrate)

Sulfonylureas Increased hypoglycemic effects (particularly with gemfibrozil) Copyright 2018 Wolters Kluwer All Rights Reserved Miscellaneous Antihyperlipidemic Drugs: Niacin and Ezetimibe 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 Copyright 2018 Wolters Kluwer All Rights Reserved 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 Copyright 2018 Wolters Kluwer All Rights Reserved 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 Copyright 2018 Wolters Kluwer All Rights Reserved Nursing Process: Diagnoses Constipation related to antihyperlipidemic drugs Risk for Imbalanced Nutrition: Less Than Body Requirements related to malabsorption of vitamins Risk for Impaired Skin Integrity related to rash and flushing Nausea related to antihyperlipidemic drugs Risk for Injury related to dizziness

Copyright 2018 Wolters Kluwer All Rights Reserved 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 Copyright 2018 Wolters Kluwer All Rights Reserved Nursing Process: Implementation #1 Promoting an optimal response to therapy:

Explain drug regimen and possible adverse reactions Emphasize the importance of following printed dietary guidelines Copyright 2018 Wolters Kluwer All Rights Reserved Nursing Process: Implementation #2 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 resins used for long-term therapy:

administer vitamins A, D in water-soluble form or parenterally Copyright 2018 Wolters Kluwer All Rights Reserved Nursing Process: Implementation #3 Monitoring and managing patient needs (cont.) 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

Copyright 2018 Wolters Kluwer All Rights Reserved Nursing Process: Implementation #4 Monitoring and managing patient needs (cont.) Potential complication: Vitamin K deficiency: include foods high in vitamin K in the patients diet Rhabdomyolysis: be alert for unexplained muscle pain, muscle tenderness, or weakness, especially if accompanied by malaise or fever Copyright 2018 Wolters Kluwer All Rights Reserved

Nursing Process: Implementation #5 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 Copyright 2018 Wolters Kluwer All Rights Reserved Nursing Process: Evaluation #1 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 Copyright 2018 Wolters Kluwer All Rights Reserved Nursing Process: Evaluation #2 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 Copyright 2018 Wolters Kluwer All Rights Reserved Answer to Question #3 False HMG-CoA reductase inhibitors are frequently called statin drugs. These drugs lower the blood level of cholesterol low-density lipoproteins (LDLs) and triglycerides. Bile acid resins and fibric acid derivatives act in a similar manner to reduce cholesterol by binding with bile so the liver will use more, putting less in the system.

Copyright 2018 Wolters Kluwer All Rights Reserved

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