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HYPERLIPIDEMIA
Jessica Ruiz
Chamberlain University
NR 508 – Advanced Pharmacology
Case Study
W.S. is a 58 year old male who presents to the office for his yearly physical exam. He was recently found to have elevated cholesterol 7 months ago but requested to alter his diet before starting medication. He reports a family history of diabetes (mother) and hypertension (father). He has no known allergies. Occasional alcohol consumption, no drug use, no current medication besides a multivitamin. Reports no regular exercise or physical activity besides walking his dog 1 block every morning and night.
Current physical exam: Ht 5’10”, Wt 100 kg, BP 135/85, HR 70, TC 280mg/dL, LDL 170mg/dL, HDL 28mg/dL, triglycerides 380mg/dL
Medication Management
What is hyperlipidemia? A disorder of lipoproteins that result in elevated total cholesterol (TC), elevated low density lipoprotein (LDL) cholesterol, elevated triglyceride level, and low high density lipoprotein (HDL) cholesterol. TC should be less than 200 mg/dL, LDL less than 100 mg/dL, HDL 60 mg/dL or greater, and triglycerides less than 150 mg/dL.
Classes
HMG-Coa Reductase Inhibitors (Statins)
Fibric Acid Analogs
Bile Acid Sequestrants
Niacin
Selective Cholesterol Absorption Inhibitors
Omega 3 acid ethyl esters
(CDC, 2015)
(Edmonds & Mayhew, 2013)
(Last, Ference, Falleroni, 2011)
HMG-Coa Reductase Inhibitors (Statins)
*** Initial Treatment
Mechanism of action (MOA): Inhibit HMG-CoA reductase, which is the key limiting step in cholesterol synthesis, used to reduce serum low density lipoprotein (LDL).
Adverse Effects (AE): elevated liver enzymes, hepatotoxicity, photosensitivity, muscle toxicity, weakness, rhabdomyolysis, myalgia, increase risk of diabetes
Contraindications: active liver disease, pregnancy, lactation, hypersensitivity
(Edmonds & Mayhew, 2013)
HMG-Coa Reductase Inhibitors (Statins)
High Intensity lowers LDL >50%
Atorvastatin (Lipitor) 40-80 mg daily
Rosuvastatin (Crestor) 20 mg daily
Moderate Intensity lowers LDL 30-50%
Atorvastatin (Lipitor) 10 mg daily
Rosuvastatin (Crestor) 10 mg daily
Simvastatin (Zocor) 20-40 mg daily
Pravastatin (Pravachol) 40 mg daily
Lovastatin (Mevacor) 40 mg daily
Fluvastatin (Lescol) 40 mg twice daily
Pitavastatin (Livalo) 2-4 mg daily
Low Intensity lowers LDL < 30%
Pravastatin (Pravachol) 10-20 mg daily
Lovastatin (Mevacor) 20 mg daily
Simvastatin (Zocor) 10 mg daily
Fluvastatin 20-40 mg daily
Pitavastatin (Livalo) 1 mg daily (American Family Physician, 2014)
HMG-Coa Reductase Inhibitors (Statins)
Interactions:
Lovastatin, pravastatin, simvastatin with gemfibrozil
Doses of simvastatin >10mg/day and doses of lovastatin >20mg/day with diltiazem or verapamil
Lovastatin should not exceed 40mg/day and simvastatin should not exceed 20mg/day with amiodarone
Atrovastatin and digoxin
Dose of simvastatin should be limited to 20mg/day when coprescribed with ranolazine
Lovastatin and simvastatin with conivaptan
Simvastatin and lovastatin should not exceed 40mg/day with ticagrelor
Lovastatin, simvastatin, and pitastatin should be avoided with cylosporine, everolimus, or sirolimus
Lovastatin, simvastatin and pitastatin should be avoided with tacrolimus
Pitastatin, lovastatin, fluvastatin, rosuvastatin should be avoided with colchicine
Simvastatin, atorvastatin and lovastatin with grapefruit juice
(Mukherjee, 2016)
Fibric Acid Analogs
MOA: Exhibits lipid lowering effect via stimulation of peroxisome proliferator activated receptor alpha which causes decrease triglycerides and increase HDL
Contraindications: active liver disease, hepatic dysfunction, primary biliary cirrhosis, preexisting gallbladder disease, hypersensitivity, nursing mothers, severe renal dysfunction
Interactions: HMG-CoA reductase inhibitors (increase risk for rhabdomyolysis), warfarin (increase hepatotoxicity), bile acid sequestrants (increase anticoagulation response)
Commonly prescribed:
— gemfibrozil (Lopid) 600 mg twice daily
AE: abdominal pain, acute appendicitis, indigestion
— fenofibrate
Fenoglide 120 mg orally daily
Lipofen 150 mg orally daily
Tricor 160 mg orally daily
Triglide 160 mg orally daily
AE: abdominal pain, nausea, abnormal liver function tests, backache, rhinitis
— fenofibric acid
Fibricor 105 mg orally daily
Trilipix 135 mg orally daily
(Gemfibrozil, 2018)
(Fenofibrate, 2018)
Bile Acid Sequestrants
MOA: Function as anion exchange resins in the intestinal lumen. Binds with bile acids in the intestine, causing an increase in hepatic synthesis of bile acids from cholesterol. The depletion of hepatic cholesterol increases hepatic LDL receptor activity, which removes LDL cholesterol from the plasma.
AE: abdominal pain, constipation (common), nausea, vomiting
Contraindications: complete biliary or bowel obstruction, hypersensitivity
Interactions: warfarin, levothyroxine, digoxin, thiazides, phenobarbital, tricyclic antidepressants (decrease absorption)
Commonly Prescribed:
— cholestyramine (Questran) 4 mg orally daily or twice daily
Interferes with fat and fat soluble vitamin A, D, E, and K, absorption (increased bleeding potential)
— colestipol (Colestid)
Oral suspension: 5 grams orally once or twice daily
Tablet: 2 grams orally once or twice daily
— colesevelam (Welchol) 1875 mg orally twice daily or 3750 mg daily
(Cholestyramine, 2018)
(Colesevelam, 2018)
Niacin
MOA: Niacin is a B-complex vitamin that involves actions to reduce esterification of hepatic triglycerides, decrease release of free fatty acids from adipose tissue, and increase activity of lipoprotein lipase. Increases HDL and reduces triglycerides, LDL, and total cholesterol.
AE: Flushing (redness, tingling, warm sensation) nausea, vomiting, hepatotoxicity, hyperglycemia, rhabdomyolysis
Contraindications: Liver disease, hypersensitivity, peptic ulcer disease, arterial bleeding, severe gout
Interactions: HMG-CoA reductase inhibitors, gemfibrozil (increase risk of rhabdomyolysis)
Commonly Prescribed: Niacin 500 mg orally daily at bedtime
(Edmonds & Mayhew, 2013)
(Niacin, 2014)
Selective Cholesterol Absorption Inhibitors
MOA: Acts as a brush border of intestinal epithelial cells of the small intestine to inhibit the absorption of cholesterol reducing hepatic cholesterol stores and increasing clearance of cholesterol from the blood.
AE: diarrhea, arthralgia, myalgia, fatigue, nasopharyngitis
Contraindications: hypersensitivity, active liver disease, pregnancy or nursing mothers when combined with a statin
Interactions: Gemfibrozil (increase bioavailability of Ezetimibe), bile acid sequestrants (decrease Ezetimibe levels) and cyclosporine (increase Ezetimibe levels)
Commonly Prescribed: Ezetimibe (Zetia) 10 mg daily
(Ezetimibe, 2018)
Omega 3 acid ethyl esters
MOA: not entirely understood – diminish the synthesis of triglycerides in the liver
AE: belching, dyspepsia, taste sense altered
Contraindications: hypersensitivity, fish or shellfish allergy
Interactions: prolong bleeding time (monitor patients who are receiving anticoagulants)
Commonly Prescribed: Lovaza 4 g daily or 2 g twice daily
(Edmonds & Mayhew, 2013)
(Omega-3-Acid Ethyl Esters, 2018)
Alternative Therapy
Lifestyle Modifications
Dietary therapy
Refer patients to a dietitian
Recommend and educate on consuming a low fat, low saturated fat, low cholesterol diet
Engaging in daily exercise
– Exercise logs
Smoking cessation
Avoid alcohol
Evidenced Based Support
Four statin benefit groups focusing on reducing the risk of atherosclerotic cardiovascular disease (ASCVD):
persons with clinical ASCVD
Persons with primary elevations of LDL levels of 190 mg/dL or greater
Persons with diabetes mellitus who are ages 40-75 with LDL levels 70-189 mg/dL without clinical ASCVD
Persons without clinical ASCVD or diabetes mellitus who have LDL levels of 70-189 mg/dL and an estimated 10 year ASCVD risk of 7.5% or greater
Prescribing medications is a risky task. It is a balance between right technical properties, what patients want, and highlighting the potential for conflicts between the different rationales for prescribing. Medications should be closely monitored and regularly reviewed.
(American Family Physician, 2014)
(Dreischulte, & Guthrie, 2012)
Barriers to Practice
Treatment decisions for racial and ethnic subgroups should be based on the level of ASCVD risk. Statin therapy is recommended for individuals in whom are most likely to provide ASCVD risk reduction on the basis of the estimated 10 year risk of ASCVD.
Risk factors and comorbidities
Advertisements/TV commercials
— Fear of adverse effects which culturally people then do not want to take medication
Lack of education
— Importance of diet, physical activity, and medication
Non adherence
(American Family Physician, 2014)
Identifying Outcomes
The primary goal of cholesterol lowering therapy is to decrease LDL
Better understanding of the disease and treatment
Monitor lab values and adjust treatment plan as needed
Maintain and healthy diet
Engage in daily physical activity
Question 1
What is contraindicated with simvastatin, atorvastatin and lovastatin?
Cranberry juice
Apple juice
Orange juice
Grapefruit juice
Question 2
What is a normal value of LDL?
90 mg/dL
110 mg/dL
120 mg/dL
160 mg/dL
Question 3
Which medication reduces the absorption of cholesterol from the intestines, reducing hepatic cholesterol stores and increasing clearance of cholesterol from the blood?
Gemfibrozil
Cholestyramine
Ezetimibe
Simvastatin
Question 4
True or False: Constipation is a common adverse effect of bile acid sequestrants?
True
Question 5
What is an acute adverse effect of niacin?
Photosensitivity
Flushing
Taste perversion
Cough
Reference
American Family Physician. (2014). ACC/AHA release updated guideline on the treatment of blood cholesterol to reduce ASCVD risk. Retrieved from http://www.aafp.org/afp/2014/0815/p260.pdf
Cholestyramine. (2018). In Micromedex 2.0 (Chamberlain University Library ed.) [Electronic version]. Greenwood Village, CO: Truven Health Analyrics. Retrieved June 6, 2018, from http:// micromedexsolutions.com.chamberlainuniversity.idm.oclc.org
Colestipol. (2018). In Micromedex 2.0 (Chamberlain University Library ed.) [Electronic version]. Greenwood Village, CO: Truven Health Analyrics. Retrieved June 6, 2018, from http:// micromedexsolutions.com.chamberlainuniversity.idm.oclc.org
Colesevelam. (2018). In Micromedex 2.0 (Chamberlain University Library ed.) [Electronic version]. Greenwood Village, CO: Truven Health Analyrics. Retrieved June 6, 2018, from http://micromedexsolutions.com.chamberlainuniversity.idm.oclc.org
Dreischulte, T., & Guthrie, B. (2012). High-risk prescribing and monitoring in primary care: How common is it, and how can it be improved?. Therapeutic advances in drug safety, 3(4), 175-184).
Edmonds, M. W., & Mayhew, M. S. (2013). Pharmacology for the primary care provider (4th ed.). Retrieved from http:// bookshelf.vitalsource.com
Ezetimide. (2018). In Micromedex 2.0 (Chamberlain University Library ed.) [Electronic version]. Greenwood Village, CO: Truven Health Analyrics. Retrieved June 6, 2018, from http:// micromedexsolutions.com.chamberlainuniversity.idm.oclc.org
Reference
Fenofibrate. (2018). In Micromedex 2.0 (Chamberlain University Library ed.) [Electronic version]. Greenwood Village, CO: Truven Health Analyrics. Retrieved June 6, 2018, from http://micromedexsolutions.com.chamberlainuniversity.idm.oclc.org
Gemfibrozil. (2018). In Micromedex 2.0 (Chamberlain University Library ed.) [Electronic version]. Greenwood Village, CO: Truven Health Analyrics. Retrieved June 6, 2018, from http://micromedexsolutions.com.chamberlainuniversity.idm.oclc.org
Last, A. R., Ference, J. D., Falleroni, J. (2011). Pharmacologic treatment of hyperlipidemia. American Family Physician, 84(5), 551-558.
Mukherjee, D. (2016). AHA statement on drug-drug interactions with statins. American College of Cardiology. Retrieved from www.acc.org
Niacin. (2018). In Micromedex 2.0 (Chamberlain University Library ed.) [Electronic version]. Greenwood Village, CO: Truven Health Analyrics. Retrieved June 6, 2018, from http://micromedexsolutions.com.chamberlainuniversity.idm.oclc.org
Omega-3-Acid Ethyl Esters. (2018). In Micromedex 2.0 (Chamberlain University Library ed.) [Electronic version]. Greenwood Village, CO: Truven Health Analyrics. Retrieved June 6, 2018, from http://micromedexsolutions.com.chamberlainuniversity.idm.oclc.org
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