Dyslipidemia Flashcards
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
Teratogen
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)
