Hyperlipidemia and Lipid Types PDF

**Hyperlipidemia and Lipid Types** **Hyperlipidemia:** - A condition characterized by high levels of lipids (fats) in the blood, including cholesterol and triglycerides - Associated with increased risk of atherosclerosis, coronary artery disease (CAD), thrombosis, CVA, pancreatitis (f...

**Hyperlipidemia and Lipid Types** **Hyperlipidemia:** - A condition characterized by high levels of lipids (fats) in the blood, including cholesterol and triglycerides - Associated with increased risk of atherosclerosis, coronary artery disease (CAD), thrombosis, CVA, pancreatitis (from triglycerides) - Increased risk of atherosclerotic cardiovascular disease = **ASCVD** risk **Cholesterol** A waxy substance found in your blood, necessary for building cell membranes and the synthesis of certain hormones but harmful in excess **Lipoprotein** **Families of Lipoproteins** 1. **LDL (Low-Density Lipoprotein)** - Major cholesterol carrier (2/3 -- ¾ is carried by LDL) - Delivers cholesterol to non-hepatic tissues - Often called \"bad\" cholesterol - Can build up in the walls of your arteries and form plaques, leading to atherosclerosis - The risk of developing CAD is directly related to increased LDL 1. **VLDL (Very Low-Density Lipoprotein)** - Another type of \"bad\" cholesterol - Carries triglycerides from liver to adipose tissue and muscle - Can also contribute to plaque buildup - Triglycerides are the main component - Majority stored in tissue as glycerol fatty acids 2. **HDL(High-Density Lipoprotein)** - Known as \"good\" cholesterol - Helps remove other forms of cholesterol from your bloodstream - Carries 1/3 to ¼ of cholesterol **Total cholesterol: \ - Drug not absorbed systemically, so side effects r/t GI tract - Constipation, bloating, flatulence - Pruritus - Fecel impaction, intestinal obstruction: will need to prescribe stool softener or fiber supplement (Metamucil) - Implications: - Encourage high fiber foods (whole grains cereals, fruits/veggies) - Mix powder into moist foods - Increase fluids (encourage 6-8 oz of fluid) - Because these are resin exchange: - Increase chance for meds & vitamins to bind if taken within 4 hours of the resin - Take meds 1 hr before or 4 hrs after - Can decrease folate levels: supplement in young women and children - **Examples: Cholestyramine, Colestipol, Colesevelam** 2. **HMG-CoA Reductase Inhibitors (Statins)**: Inhibit the enzyme HMG-CoA reductase, reducing cholesterol synthesis in the liver - This depletes intracellular cholesterol - The cell then looks to the extracellular space for the cholesterol it needs - Result is lowering of plasma cholesterol and LDL levels - Absorption & Distribution: High first-pass effect, Highly protein bound - Metabolism & Excretion: metabolized by the live, excreted primarily in the feces, 10% eleminted in the urine - IR forms best absorbed after meals - ER forms are impaired by food - **Examples: Lovastatin, Pravastatin, Atorvastatin, Simvastatin, Fluvastatin, Rosuvastatin (Rosuvastatin is a 2^nd^ generation statin)** 3. **Fibric Acid Derivatives (Fibrates)**: Reduce triglycerides by increasing the enzyme lipoprotein lipase (which breaks down cholesterol) - Reduce triglycerides by 35-53% - Raise HDL levels by 15-25% - Effect on LDL lower by 6-20% (or raise slightly) - Used in combination with statins for those with severe increased TG levels (TG \500) - **Usually prescribed for those with hypertriglyceridemia severe enough to increase the risk of pancreatitis** - Tend to concentrate bile in the gallbladder leading to increase risk for cholelithiasis (gall stones) - Contraindicated in patients who already has preexisting gall bladder disease or hepatic dysfunction - These drugs are teratogenic in animal studies - Adverse Effects: - Abdominal pain and diarrhea - cholelithiasis - Liver tumors - Implications - Monitor lab testing including LFTs - Monitor for signs of cholelithiasis - Intolerance to fatty foods - Nausea/vomiting - RUQ abd pain - Clay-colored stool - Low grade fever - Drug Interactions: - May potentiate effects of oral anticoagulants - **Gemfibrozil- inhibits metabolism of most statins (increasing risk of myopathy & rhabdo)\*\*\*** - **Examples: Gemfibrozil, Fenofibrate, Clofibrate** 4. **Nicotinic Acid (Niacin- Vitamin B3)**: MOA on lipid levels unknown, but thought that it inhibits lipolysis in adipose tissue - Decreases circulating fibrinogen levels and increases tissue plasminogen: end result is a decrease risk of thrombosis formation - Triglycerides and VLDL levels reduced by 25-35% in 1-4 days - LDL reduction in 5-7 days - HDL increases 15-35% (better than any other drug) - Used in treating high triglyceride levels - Dose of niacin needed to treat hyperlipidemia is a much higher dose than is used to treat niacin deficiency - As a vitamin the dose is 25mg - A dose of 2000-3000mg is needed to decrease LDL - Doses of 1200-1500 mg/day needed to decrease TG and increase HDL - Adverse Effects (many due to high required dose) - Intolerable to many patients and leads to non-compliance - Peripheral vasodilation and transient flushing (d/t histamine release and mediated thru prostaglandins- recommended patients take 325mg ASA tablet or 200mg Ibuprofen 30 min prior to decrease symptoms - GI irritation - Myalgias (muscle pain) when combined with statins - **Hepatotoxicity: exclusively with sustained release products of doses \1500mg** - Sustained release products are classified as a dietary supplement (not monitored by FDA) - Nicotinamide (OTC Niacin) has no lipid lowering effect - Usually not prescribed in diabetics d/t increase blood sugar levels - Rapidly absorbed in the intestine 5. **Cholesterol Absorption Inhibitors**: Inhibit (block) the absorption of dietary cholesterol in the small intestine and biliary cholesterol without working through the bile acids - Acts on brush border of small intestine - Decreases hepatic cholesterol stores - Decrease LDL by 17% - Newest on the market - Does not affect triglycerides or HDL - Given once daily (monotherapy or combination with statins) - Clinical trials showed no improvement outcomes in CAD and actually worsened artery wall thickness - Use as a last resort - Precautions & Contraindications: - Active liver disease - Persistently elevated liver enzymes - Restricted to children 10 years or older - Adverse Effects: - Abdominal pain - Diarrhea (severe) - Back pain - Sinusitis - Associated with skeletal defects in animal studies - **Example: Zetia, Ezetimibe** **\ ** **Benefits of Statin Therapy** \*LDL cholesterol by 20-60% \*Raising HDL by 5-10%, \*Lowers Triglycerides 10-33%: Additional benefits of statin therapy: - Stabilize plaque in blood vessels - Statins have anti-inflammatory effects- CRP levels will fall with statin therapy - Decrease thrombogenicity of blood (decreasing clot formation) - stabilize plaques in arteries - reduce the risk of heart attack and stroke (Simvastatin, Atorvastatin, Rosuvastatin) - block vasoconstrictive effects of the amyloid-beta protein (protein associated with Alzheimer') - may be protective against dementia caused by blood vessel vasoconstriction - ? ability to lower incidence of colorectal cancer **Side Effects of Statins (more serious side effects seen with use of Rosuvastatin- crestor)** Common side effects include: - Non-specific aches and muscle pain - Elevated LFT's (hepatotoxicity) - Increased blood sugar levels (new onset diabetes rare) - Rarely, they can cause severe muscle damage (rhabdomyolysis) **ACC/AHA Statin Safety Recommendations** - Selection of statin based on patient characteristics, level of ASCVD risk, & potential for adverse effects - Predisposing characteristics of serious adverse effects: - Multiple comorbidities - H/O previous statin intolerance or muscle disorders - Unexplained ALT elevation \>3 X upper limits of normal - \>75 y/o - Grapefruit juice (limes and tangelos) can inhibit metabolism of statins - This effect can persist up to 3 days after ingestion of the juice - How much juice needs to be consumed: varies, but approx. 8oz will do it - Baseline measurement of ALT should be performed before initiating therapy and during therapy if symptoms of hepatotoxicity arise - Evaluate for new-onset diabetes according to current diabetes screening - May be harmful to initiate Simvastatin at 80mg daily or increase the dose to 80mg daily - Management Algorithm for muscle symptoms - Prior to initiating obtain a history of prior or current muscle symptoms - Development of severe muscle symptoms or fatigue during statin therapy: - Promptly D/C statin - Obtain CK, creatinine and urinalysis for myoglobinuria - Development of mild to moderate muscle symptoms: - D/C statin until symptoms can be evaluated - Evaluate patient for conditions that might increase risk for muscle symptoms - If symptoms resolve: - Give original or lower dose of the same statin to establish causal relationship - If relationship exists: D/C original statin and use lower dose of a different statin - If after 2 months, symptoms persist or CK levels don't resolve, look for other causes (if other causes, restart statin at original dose) **Rhabdomyolysis, Myopathy, and Muscle Aches** - **Rhabdomyolysis (\