Lipid Lowering

Question 1

What two statins are prodrugs?

Answer 1

lovastatin

simvastatin

Question 2

Effect of omega-3 fatty acid supplements on blood lipids

Answer 2

decrease TG

Question 3

Effect of statins on blood lipids

Answer 3

reduce LDL

modest reduction in TG and increase in HDL

Question 4

higher intensity lipid lowering statin

Answer 4

atorvastatin

Question 5

metabolized by CYP3A4

Answer 5

atorvastatin

Question 6

metabolized by sulfating (NOT p450 dependent)

Answer 6

pravastatin

Question 7

except atorvastatin, statins are administered ______ (time of day), when cholesterol biosynthesis takes place

Answer 7

QHS

Question 8

half life:
atorvastatin _______ hrs
pravastatin ________ hrs

Answer 8

14 h (take any time)
2 h (take QHS)

Question 9

statin that is excreted unchanged in urine

Answer 9

pravastatin

Question 10

statin that is not protein bound

Answer 10

pravastatin

Question 11

effect of taking food with drug

Answer 11

decreased absorption of drug

Question 12

statin that crosses BBB

Answer 12

atorvastatin

Question 13

well known adverse effect of atorvastatin, when combined with gemfibrozil (inhibits uptake) or drugs that inhibit CYP3A4 (TONS!)

Answer 13

myopathy/myalgia

rhabdomyolysis

Question 14

statin that is hydrophilic and hepatoselective

Answer 14

pravastatin

Question 15

cholesterol absorption blocker at brush border (inhibits Niemann-Pick C1-Like 1)

Answer 15

ezetimibe (and its glucuronirated metabolite)

increases expression of LDL-receptor (increased clearance)

Question 16

effect of ezetimibe on lipid levels

Answer 16

decrease LDL, especially as adjunct

combined with statin - no P450 involvement

Question 17

half life:

ezetimibe

Answer 17

22 hours

long due to enterohepatic circulation

Question 18

effect of cholestyramine on lipid levels

Answer 18

reduce LDL

modest increase in HDL and TG

Question 19

binds bile acids in the GI –> excretion

Answer 19

cholestyramine

up regulates LDL-receptor to increase conversion of cholesterol to bile

Question 20

contraindication to cholestyramine

Answer 20

hyperTG

Question 21

give this medication 1 hr after or 2 hrs before other drugs

Answer 21

cholestyramine

can bind and impair absorption of other drug

Question 22

effect of niacin on lipid levels

Answer 22

increases HDL

lowers TG and LDL

Question 23

inhibits lipolysis in adipose tissue for transport to liver (for VLDL synthesis)

Answer 23

niacin (vitamin B3) at high doses

Question 24

contraindications for niacin

Answer 24

pregnancy

caution with existing liver and GI issues

Question 25

adverse effect of niacin

Answer 25

flushing (declines over 1-2 weeks)

hepatotoxicity (heavy first pass metabolism)

Dyspepsia (huge doses!)

Question 26

effect of fibrates on lipid levels

Answer 26

lower TG

Question 27

only fibrate shown to impact outcomes:

Answer 27

gemfibrozil

Question 28

gemfibrozil MOA

Answer 28

agonist for PPAR-alpha receptor (transcription factor)

essentially - decreases TG synthesis and increases clearance

Question 29

half life gemfibrozil

Answer 29

1.1 hours

Question 30

adverse effects of gemfibrozil

Answer 30

myopathy
GI discomfort
DRUG interactions due to inhibition of transporter (warfarin, OCP)

Question 31

contraindications for gemfibrozil

Answer 31

pregnancy

children

Question 32

best drug for increasing HDL

Answer 32

niacin

Question 33

best drug for lowering LDL

Answer 33

statins

Question 34

best drug for lowering TG

Answer 34

fibrates, niacin, omega-3

only gemfibrozil clinically significant

Question 35

What does PCSK9 do?

Answer 35

binds to LDL-R leading to its degradation

Question 36

evolocumab (Repatha)

Answer 36

PCSK9 inhibitors

Question 37

problems with evolocumab

Answer 37

injected only
expensive
nasopharyngitis

?seem not too efficacious?

Question 38

indication for evolocumab (who gets it?)

Answer 38

familial homozygous hypercholesterolemia