dyslipidemia

Question 1

statins MOA and when to take

Answer 1

inhibition of HMG-CoA reductase -> no conversion of HMG-CoA to mevalonate (RLS in cholesterol biosynthesis)
take in the evening; cholesterol synthesis is max from 12 - 2 AM

Question 2

statin metabolism

Answer 2

metabolized by CYP3A4
AE’s increased with concomitant use of CYP3A4 inhibitors, macrolides, azole antifungles, amiodarone, HN protease inhibitors, and gemfibrozil

Question 3

statin AE

Answer 3

increase in serum transaminases, myalgia, weakness, rhabdomyolysis

Question 4

statin contraindications

Answer 4

acute liver disease, persistent unexplained increased serum transaminases, pregnancy

Question 5

statin monitoring

Answer 5

LFTs (baselines and as clinically indicated thereafter); discontinue if >3x ULN
CK levels (baseline and if sxs appear); discontinue if >10x ULN

Question 6

statin avoiders

Answer 6

grapefruit juice (interferes with CYP3A4)
red yeast rice (contains statin active ingredient)

Question 7

bile acid-binding resins agents

Answer 7

holesyramine, colestipol, colesevelam

Question 8

BARs MOA

Answer 8

increase LDL catabolism and decrease cholesterol absorption
bind bile acids to prevent reabsorption -> increase cholesterol-using bile synthesis -> increase LDL uptake and clearance

Question 9

BARs ADME

Answer 9

powder form mixed with water

not systemically absorbed

Question 10

BARs AE’s

Answer 10

GI (dyspepsia, bloating, abdominal discomfort)
hepatic (hypertriglyceridemia, increased serum transaminases)
pancreatitis

Question 11

BAR absorption interactions

Answer 11

levothyroxine, warfarin, verapamil, phenytoin (administer 1 hr before or 3-4 after BAR)

Question 12

fibric acid derivatives agents

Answer 12

gemfibrozil, fenofibrate, fenofibric acid

Question 13

fibric acid derivatives MOA

Answer 13

increase VLDL clearance and decrease synthesis
activate nuclear transcription factor perioxisome proliferator activated receptor alpha (PPAR-alpha) on hepatocytes -> regulate lipid and glucose metabolism genes -> inhibit lipolysis and decrease hepatic fatty acid uptake

Question 14

fibric acid derivatives AE’s

Answer 14

increased serum transaminases, myalgia / weakness

Question 15

fibric acid derivatives contraindications

Answer 15

significant hepatic or renal dysfunction, primary biliary cirrhosis, pre-existing gall bladder disease

Question 16

fibric acid derivatives intreactions

Answer 16

gemfibrozil > fenofibrate due to hepatic metabolism

Question 17

fibric acid derivatives monitoring

Answer 17

LFT’s - discontinue if > 3 x ULN

Question 18

Niacin (nicotinic acid) MOA

Answer 18

decrease LDL and VLDL synthesis
inhibition of triglyceride synthesis, inhibition of lipolysis, enhance LPL activity -> increase VLDL clearance
enhance HDL synthesis by blocking apoA breakdown

Question 19

Niacin (nicotinic acid) AE’s

Answer 19

flushing (prostaglandin mediated)

dyspepsia, peptic ulcer disease, nausea, hyperuricemia, decreased glucose tolerance, hepatotoxicity

Question 20

Niacin (nicotinic acid) contraindications

Answer 20

acute liver disease, pregnancy, gout

Question 21

cholesterol absorption inhibitor agent and MOA

Answer 21

ezetimibe
decrease cholesterol and LDL
inhibit cholesterol absorption at small intestine brush border -> decreased cholesterol delivery -> increased LDLR and clearance
not used much

Question 22

cholesterol absorption inhibitor AE’s

Answer 22

well tolerated; increases incidence of myopathy and increased transaminases when given with statin

Question 23

Fish oil MOA

Answer 23

reduce hepatic triglyceride synthesis and increase clearance

Question 24

fish oil AE’s

Answer 24

dyspepsia, taste aversion, prolonged bleeding time

Question 25

overall effects of statins

Answer 25

decreased cholesterol, decreases LDL, decreased trigs, increased HDL

Question 26

overall effects of BARs

Answer 26

decreased cholesterol, decreased LDL, increased VLDL

Question 27

overall effects of fibrates

Answer 27

decrease triglycerides, decrease cholesterol

Question 28

overall effects of niacin

Answer 28

decreased trigs, decreased cholesterol, increased HDL

Question 29

overall effects of Ezetimibe

Answer 29

decreased cholesterol, decreased LDL