Treatment Of Lipid Disorders

Question 1

Statins (HMG Co-A Reductase Inhibitors)

Answer 1

Mechanism: Lowers Liver cholesterol, increases LDLR, plaque stabilization, anti-inflammatory
-lowers TC, LDL, TG and raises HDL
-CV Event and Mortality Benefit
Side Effects/Interactions:
-increases LFTs
-myositis
-rhabdomyolysis (Rare): increased risk with GFR <30, fibrate use, cyclosporin. Decreased risk: pravastatin and fluvastatin
-FDA warnings: Diabetes, memory loss/confusion, simvastatin 80mg
-interactions: gemfibrozil, amlopipine, amiodarone-rhabdo; Warfarie (increased INR) with all except pravastatin, fluvastatin, pitavastatin

Question 2

PCSK9 Inhibitors

Answer 2

MOA: interferes with PCSK9 binding of LDLR so increases LDLR and decreases LDL
-Decreases TDC, LDL, TG and increases HDL
-CV Event Benefit
Side Effects/interactions:
-local injection site Reactions

Question 3

Ezetimibe

Answer 3

MOA: decreases cholesterol absorption at the brush border of small intestine, decreases liver cholesterol and increases LDLR
-decreases TC, LDL and TGs and increases HDL
-CV event benefit
Interactions/Side Effects:
-minimal; diarrhea, increased LFTs with statin
-decreased absorption with cholestyramine; no effect on fat soluble vitamins

Question 4

Bile Acid Resins

Answer 4

MOA: binds bile salts in the gut, decreases enterohepatic reuptake, decreases liver cholesterol and increases LDLR
-decreases TC, LDL, TG and increases HDL
Side Effects/Interactions
-constipation, nausea, bloating
-decreased absorption of statins, niacin, fibrates, antibiotics, warfarin, fat soluble vitamins, digoxin, thiazides, Beta-blockers

Question 5

CETP Inhibitors

Answer 5

MOA: increase HDL by blocking transfer of Cholesterol from HDL to VLDL/LDL
-Decreases TC, LDL, TG and increases HDL
-CV Event Benefit
Side Effects/Interactions:
-increased BP, myositis, decreased GFR

Question 6

Fibrates

Answer 6

MOA: increases LPL and decreases apoCIII, decreasing VLDL TGs and increasing apoA1 and A2 slightly to increase HDL
-decreases TC, TG, LDL and increases HDL
Side Effects/Interactions
-avoid/use with caution with CKD
-with statins: rhabdo, CI with simvastatin
-Gemfibrozil: dyspepsia, abdominal pain, gallstones, diarrhea
-fenofibrate: increased LFTs, nausea, abdominal pain, gallstones

Question 7

Omega-3 Fatty Acids

Answer 7

MOA: decrease the rate of VLDL secretion from teh liver
-Decreases TC, TG, LDL and increases HDL
Minimal Side effects

Question 8

Niacin

Answer 8

MOA: inhibits TG (and VLDL) synthesis in liver in several ways including decreased release of FFAs from fat and decreased LPL
Side Effects/interaction:
-flushing (ASA helps), pruritis, nausea, diarrhea, myositis, rhabdo especially with statins, increased ALT and hepatotoxicity