Lecture 13: Cholesterol Medication

Question 1

Apo CII vs Apo CIII

Answer 1

both proteins found in lipoproteins , act as ligands for receptors and enzymes to mediate action

CII activates lipoprotein lipase
CIII inhibits LPL

LPL cleaves TGs from lipoproteins

Question 2

Statins MOA

Answer 2

competitive inhib of HMg-CoA reductase
- depletes sterol pools
- increases LDLR
- decreases LDL (more cholesterol excreted in bile)

Question 3

most effective statins on the market

Answer 3

atorvastatin - long half life

rosuvastatin - most potent on the market, no hepatic metabolism

Question 4

contraindications for statin use

Answer 4

• LDL R homozygous deficiency
• never in pregnancy (need cholesterol for fetus)

Question 5

which drugs target cholesterol synthesis

Answer 5

• statins (inhibit HMh-CoA reductase)
• bempedoic acid (inhibit ATP citrate lyase, upstream of HMg-CoA)

Question 6

Which drugs act synergistically with statins (3)

Answer 6

drugs that inhibit cholesterol uptake
cholestyramine and colestipol, ezetimibe
- can reduce dosage of statin then

Question 7

cholestyramine and colestipol

Answer 7

cationic resins that bind to bile acids. increase excretion of bile acids. This causes de novo production of bile acids from cholesterol (depletes sterol pools)

adverse FX - might impair absorption of other drugs (need to take before or after statins), diarrhea and weight loss

Question 8

ezetimibe

Answer 8

directly blocks cholesterol absorption in small intestine
- not really used in monotherapy more often adjunct to statin

Question 9

Niacin / nicotinic acid

Answer 9

undefined MOA
- essentially results in less VLDL production
- only lipid lowering drug that can lower Lp(a) levels

side FX of flushing, hyperglycemia, GI upset, liver dysfunction which is why it’s really only prescribed for genetic Lp(a)

Question 10

fibric acid derivative drugs

Answer 10

clofibrate, fenofibrate, gemfibrozil
- stimulate PPAR alpha which then upregulates gene transcription of genes associated w lipid metabolism
- more lipoprotein lipase, decrease apoC-III expression (the inactivator of LPL), more fatty acid oxidation

Question 11

PCSK9 inhibitors

Answer 11

PCSK9 - enzyme that degrades LDL-Rs
- evolocumab inhibits PCSK9 so increases LDLRs

Question 12

berberine

Answer 12

inhibits PCSK9 gene transcription
is a plant sterol

Question 13

next gen lipid lowering drugs

Answer 13

pelacarsen - antisense oligonucleotide for apo(a) mRNA, reduces Lp(a)