Hyperlipidemia Flashcards
What are the two main types of lipids?
Cholesterol and triglycerides.
Why do lipids need transporters (such as lipoproteins) to move around the body?
They are water-insoluble.
What are lipoproteins?
Spherical macromolecules of lipid and apolipoprotein.
Where is each type of lipoprotein synthesized?
- Chylomicron: intestine.
- VLDL and LDL: liver.
- HDL: peripheral tissues.
What is the function of chylomicrons?
Carry exogenous triglycerides and cholesterol from the gut to blood circulation.
What does VLDL transport?
Endogenous triglycerides from the liver to blood circulation.
What is the role of LDL?
Carry endogenous cholesterol from the liver to blood circulation.
What does HDL do?
Carries cholesterol from peripheral tissues and blood to the liver for metabolism and/or secretion.
What are the three lipid-related factors correlated with coronary heart disease (CHD)?
Elevated LDL-C, elevated triglycerides, low HDL-C.
What do plasma lipids mostly consist of?
Lipoproteins.
What are lipoproteins a combination of?
Triglyceride or cholesterol with apoprotein.
List the clinically important lipoproteins in decreasing order of atherogenicity.
LDL > VLDL > chylomicrons > HDL.
What is the primary effect of HMG CoA reductase inhibitors on LDL-C?
Lower elevated LDL-C.
What is the result of lowering LDL-C with HMG CoA reductase inhibitors?
Reduction in coronary events and death from CHD.
How are HMG CoA reductase inhibitors commonly known?
Statins.
Name some common statins.
Lovastatin, Simvastatin, Pravastatin, Atorvastatin, Fluvastatin, Pitavastatin, Rosuvastatin.
Which statin is the most effective?
Rosuvastatin.
How do HMG CoA reductase inhibitors (statins) lower LDL cholesterol?
Statins competitively inhibit HMG CoA reductase, the rate-limiting step in cholesterol synthesis, depleting intracellular cholesterol. This increases cell surface LDL receptors, which bind and internalize circulating LDLs, leading to increased LDL catabolism.
What additional effects do HMG CoA reductase inhibitors have?
Decrease triglyceride levels, increase HDL cholesterol levels in some patients.
What is the primary treatment option for hypercholesterolemia?
Statins.
For which patients are statins considered first-line treatment?
Patients with elevated risk of atherosclerotic cardiovascular disease (ASCVD).
What is the effect of statins on plasma cholesterol levels?
They lower plasma cholesterol levels in all types of hyperlipidemias.
When should statins be administered and why?
In the evening, because major cholesterol synthesis happens in the early morning.
What are the common adverse effects of statins?
Elevated liver enzymes (hepatotoxicity), myopathy, and rhabdomyolysis.
How can statins affect warfarin?
They may increase the effect of warfarin by inhibiting its metabolism.
Why are statins contraindicated during pregnancy and lactation?
Due to potential adverse effects on the fetus and infant.
By what percentage does niacin reduce LDL-C?
20%.
By what percentage does niacin lower triglycerides?
35%.
What is niacin the most effective agent for?
Increasing HDL-C.
How does niacin reduce the production of free fatty acids?
By inhibiting lipolysis in adipose tissue.
What does the liver use circulating free fatty acids for?
As a major precursor for triglyceride synthesis.
How does reduced liver triglyceride levels affect hepatic VLDL production and LDL-C plasma concentrations?
Decreases hepatic VLDL production, which reduces LDL-C plasma concentrations.
What plasma levels does niacin lower and what condition is it used to treat?
Lowers plasma levels of both cholesterol and triglycerides; used in the treatment of familial hyperlipidemias.
What is the most common side effect of niacin?
Intense cutaneous flush and pruritus.
What causes the cutaneous flush and pruritus from niacin, and how can it be managed?
Production of prostaglandins; managed by taking NSAIDs before administering niacin and taking it at night.
How does niacin affect uric acid secretion and what does this predispose to?
Inhibits tubular secretion of uric acid, predisposing to hyperuricemia and gout.
Why should niacin be avoided in hepatic disease and used with caution with statins?
Due to the risk of hepatotoxicity.
What are fenofibrate and gemfibrozil derivatives of?
Fibric acid.
What effects do fenofibrate and gemfibrozil have on lipid levels?
Lower serum triglycerides and increase HDL levels.
Which agents are most efficacious in lowering triglycerides?
Niacin and fibric acid derivatives.
What receptors do fibrates activate to regulate lipid metabolism?
Peroxisome proliferator-activated receptors (PPARs).
How do fibrates decrease triglyceride concentrations?
By increasing the expression of lipoprotein lipase.
What is the clinical use of fibrates?
Treatment of hypertriglyceridemias.
What are the most common adverse effects of fibrates?
Mild gastrointestinal (GI) disturbances.
What risk is associated with the increased biliary cholesterol excretion caused by fibrates?
Predisposition to form gallstones.
What serious adverse effects may occur when gemfibrozil is taken with statins?
Myopathy and rhabdomyolysis.
What is the primary effect of bile acid sequestrants (resins) on LDL cholesterol?
Significant LDL cholesterol-lowering effects.
How do the benefits of bile acid sequestrants compare to those of statins?
The benefits are less than those observed with statins.
What do cholestyramine, colestipol, and colesevelam bind to in the small intestine?
Bile acids and bile salts.
How is the resin/bile acid complex excreted from the body?
Excreted in the feces.
What is the effect of lowering bile acid concentration on hepatocytes?
Increases conversion of cholesterol to bile acids.
What is the consequence of increased conversion of cholesterol to bile acids?
Decreased intracellular cholesterol concentrations.
For what conditions are bile acid-binding resins useful?
Treating type IIA and type IIB hyperlipidemias.
In what combination are bile acid-binding resins often used?
In combination with diet or niacin.
For what additional condition is colesevelam indicated and why?
Type 2 diabetes due to its glucose-lowering effects.
What is the solubility and molecular weight characteristic of bile acid sequestrants?
Insoluble in water and have large molecular weights.
How are bile acid sequestrants processed after oral administration?
They are neither absorbed nor metabolically altered by the intestine.
How are bile acid sequestrants excreted from the body?
Totally excreted in feces.
What are the most common side effects of bile acid-binding resins?
GI disturbances such as constipation, nausea, and flatulence.
How do bile acid-binding resins affect the absorption of vitamins and drugs?
They may impair the absorption of fat-soluble vitamins (A, D, E, K) and interfere with the absorption of many drugs.
Why are bile acid-binding resins contraindicated in patients with significant hypertriglyceridemia?
Because they may raise triglyceride levels.
What is the mechanism of action of ezetimibe?
Selectively inhibits absorption of dietary and biliary cholesterol in the small intestine.
How does ezetimibe affect LDL and HDL cholesterol levels?
Lowers LDL cholesterol and increases HDL.
Why does ezetimibe increase HDL levels?
Due to increasing the clearance of cholesterol from the blood.
How common are adverse effects with the use of ezetimibe?
Adverse effects are uncommon.
What are omega-3 polyunsaturated fatty acids (PUFAs) used for?
Triglyceride lowering.
What is a potential adverse effect of omega-3 PUFAs on cholesterol?
May raise LDL-C.
How do essential fatty acids affect VLDL and triglyceride synthesis?
Inhibit VLDL and triglyceride synthesis in the liver.
What are the primary sources of omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)?
Marine sources such as tuna, halibut, and salmon.
What are the most common side effects of omega-3 PUFAs?
GI effects (abdominal pain, nausea, diarrhea) and a fishy aftertaste.
In which patients can the bleeding risk be increased with omega-3 PUFAs?
Those concomitantly taking anticoagulants or antiplatelets.
