Lipoprotein Drugs

Question 1

Who should be screened for lipids?

Answer 1

adults > 20

Question 2

LDL cholesterol tx targets

Answer 2

CHD/CHD equivalents: LDL <160

Question 3

T/F Non-hdl cholesterol is a better predictor of CHD than ldl-c

Answer 3

T –> includes all other cholesterol components/remnants/etc.

Question 4

3 classes of drugs that lower LDL

Answer 4

1. statins -hmg CoA reductase inhibitors
2. CAI, ezetimibe - cholesterol absorption inhibitors
3. BAS -bile acid sequestrants

Question 5

Rate limiting step in production of cholesterol

Answer 5

hmg coa reductase –> produces mevalonate from acetyl coA –> target of statins

Question 6

Statins MOA

Answer 6

statin appendage mimics HMG CoA and binds reversibly to enzyme thereby inhibiting true substrate (binds w/ higher affinity than substrate)

Question 7

How do statins regulate the LDL receptor?

Answer 7

inhibit hmg coa reductase –> reduce cholesterol in liver –> upregulate LDLR to bring more cholesterol in –> suck LDL out of blood

Question 8

First line tx for ldl reduction

Answer 8

statins

Question 9

Adverse effects of statins

Answer 9

elevated hepatic enzymes (modestly and transiently), muscle-related (myalgia, myopathy, rhabdomyolysis)

Question 10

myalgia

Answer 10

muscle ache/weakness w/o CK elevation

Question 11

myopathy

Answer 11

muscle symptoms w/ elevation in CK

Question 12

rhabdomyolysis

Answer 12

muscle symptoms with Ck elevation and creatinine elevation

Question 13

Who is at risk of muscle-related issues with statins

Answer 13

frail older women with renal insufficiency, hypothyroidism, polytherapy

Question 14

Key molecular mechanism for cholesterol absorption

Answer 14

NPC1L1 from lumen into enterocyte

Question 15

Ezetimibe MOA

Answer 15

blocks NPC1L1 and inhibits cholesterol absorption –> reduces cholesterol in liver –> upregulate LDLR –> suck even more cholesterol from blood

Question 16

Adverse effects of Ezetimibe

Answer 16

elevated liver enzymes

Question 17

What is IBAT

Answer 17

ileal bile acid transporter that recycles bile to the liver from the gut –> reducing bile acid flow via IBAT forces liver to produce more bile acids and shunt cholesterol away from blood

–>cholestyramine, colestipol, colesevelam bind bile acids and end up in feces (safe to use in pregnant women, etc)

Question 18

Adverse effects of BAS

Answer 18

bloating, constipation, flatulence, raise TG (via transcriptional effects)

Question 19

ASO to apoB MOA

Answer 19

antisense oligonucleotide targets apoB –> reduces VLDL production

Question 20

small molecule MTP inhibitor MOA

Answer 20

reduces VLDL by reducing loading of TG to apoB

Question 21

3 classes of drugs that treat TG-HDL axis

Answer 21

1. fibric acid derivatives
2. omega 3 fatty acids
3. nicotinic acid

Question 22

Fibric acid derivatives MOA

Answer 22

e.g. phenofibrate –> activate PPARalpha (nuclear receptor) –> increased HDL production, reduced VLDL production, increased VLDL clearance (via a lot of different pathways)

Question 23

Adverse effects of fibrates

Answer 23

myalgias, liver enzymes, but otherwise well tolerated

Question 24

Omega 3 MOA

Answer 24

EPA and DHA –> reduce TG and raise HDL (for preventing pancreatitis but not clear evidence on cv risk)

Question 25

nicotinic acid MOA

Answer 25

niacin/vitamin B3 --> blocks adipose lipolysis --> reduce FFA --> reduce liver flux --> reduce VLDL production *increases HDL, reduces TG, reduces LDL, reduces Lp(a)

Question 26

Adverse effects of niacin

Answer 26

flushing, hyperuricemia, hepatotoxicitiy, contraindicated in insulin resistance

Question 27

CETP inhibitors MOA

Answer 27

inhibits transfer of cholesterol out of HDL into LDL --> huge elevation in HDL and reduction of LDL