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Flashcards in Dyslipidemia Deck (15):

What is the best lipid target for preventing heart disease?

Statins: target cholesterol synthesis

Prevent coronary events and prevent mortality


Can increasing HDL help treat heart disease?

No- this has not been shown to help in human studies


What is the mechanism of action of statins?

They go to the active site of HMG-CoA reductase & inhibit it --> inhibition of cholesterol synthesis

Leads to reduced intracellular cholesterol and increased LDL receptor activity/enhanced LDL clearance

LDL rduciton, TG reductoin, HDL increase


What's the pharmacology of statins? (site of action, clearance)

Hepatic extraction --> takes the drug to the liver, which is their pharmacologic site of action

Atorvastatin, Lovastatin, Simvastatin inhibit CYP3A4 --> no grapefuit juce or other drugs that inhibit this

All inhibit glucuronidation --> gemfirbozil is contraindicated


What are the pleiotropic (nonlipid) effects of statins?

Reduced LDL is believed to account for nearly all of the CHD benefit seen wtih statins-- BUT they also:

increase NO synthesis

Inhibit vasc sm m prolif

Reduced matrix metalloproteinase activity which improves plaque stability

Anti-inflammatory effects


What are the side effects of statins?

Diabetes in 1/100-1/500

Transaminase elevation --> hepatitis

Acute myosits (inflammation of sk m --> weakness) 0.1%, more frequent when pt also takes cyclopsorin A (immunosuppressant), fibrate, niacin, macrolide, antibiotics



What are bile acid sequestrants? Mechanism of action?

Drug that reduces cholesterol: Reduces hepatic intracellular cholesterol, increases LDL receptor activity, enhancing LDL clearance

Stays in the gut- not readily absorbed: SE include epigastric distress, constipation, drug adsorption (digoxin, thiazides, thyroxine, warfarin, statins), hypertriglyceridemia

Beneficial SE: reduces blood glucose levels in type 2 diabetes

Shown to prevent development of CHD



What is the mechanism of ezetimibe?

Cholesterol absorption inhibitor in sm intest (does not affect other fat absorption & saturated fat is #1 determinant of cholesterol levels)

Reduces hepatic intracellular cholesterol, increases LDL receptor activity, enhancing LDL clearance

Interacts with NPC1-L1 (small intestinal cholesterol transporter)


Where does most of your intestinal luminal cholesterol come from?

Mostly from bile+ mucosal epethelia!!! Only about 20% comes from diet


What is nicotinic acid? How does it work?

Niacin: binds G protein coupled receptor --> reduced cAMP levels --> reduced hormone sensitive lipase --> reduced lipolysis in adipocytes & reduced hepatic secretion of VLDL

Also reduced triglyceride synthesis via inhibited activity of diglycerol acyl transferase-2

Overall: reduced VLDL/TG (50%), reduced LDL cholesterol (30%), increased HDL cholesterol (25-50%)

Reduces mortality and reduces coronary disease

SE: flushing, dry skin, gastritis, hepatitis, hyperglycemia, hyperuricemia, gout


What is the mechanism of action of fibric acid?

Reducse VLDL, increases HDL

Not the best choice for maximum LDL reduction bc there's only a small reduction when bsln TG is normal and can increase LDL when bsln TG is high

Gemfibrozil= one example and has been shown to decrease CHD death/MI

SE: myopathy esp when used w/statin, GI upset, cholesterol gallstones, elevated LDL, decreased libido


When should you use fibrates?

If pt has diabetes or insulin resistance/metabolic syndrome who also have low HDLc and high TG


How should you treat a patient with low HDL?

Increasing exercise via exercise, weight loss, quit smoking can increase HDL

Decreasing LDL is primary goal

Pharmacological increase of HDL has not been shown to work better than management of LDL via statins alone


What are normal levels of TG's?

Normal: <150 mg/dl

Borderline high: 150-199

High: 200-499

Very high: >500


How should you treat high TGs?

(1) diet

(2) exercise

(3) drugs: nicotinic acid, fibric acid drugs, statins, fish oils (inhibit VLDL secretion)