Lipid Disorders Treatment

Question 1

Primary chylomicronemia

Answer 1

Defect: defective removal of CM (ApoCII, LPL Defect)

Manifestation: chylomicrons, elevated VLDL, pancreatitis

Question 2

Familial hypertrigkyceridemia

Answer 2

Defect: defective metabolism of VLDL (LPL defect)

Manifestation: elevated VLDL, hypertriglyceridemia, pancreatitis

Question 3

Familial Dysbetalipoproteinemia

Answer 3

Defect: defective metabolism of VLDL, Chylomicrons, ApoE defect (E2/E2 alleles)

Manifestation: VLDL and CM remnants (IDL) elevated, cholesterol and TG elevated 1:1, atherosclerosis

Question 4

Familial Combined Hyperlipidemia (FCH)

Answer 4

Defect: overproduction of ApoB (VLDL)

Manifestation: variable phenotype, elevated VLDL, LDL, or both; premature atherosclerosis

Question 5

Familial Hypercholesterolemia (FH)

Answer 5

Defect: LDL receptor, ApoB defect, decreased receptor mediated removal of LDL from plasma

Manifestation: LDL increased, premature atherosclerosis

Question 6

Desirable cholesterol levels

Answer 6

total cholesterol < 200
LDL cholesterol < 130
HDL cholesterol > 40

Question 7

Statin MOA

Answer 7

HMG-CoA Reductase Inhibitors; inhibits the rate limiting step of cholesterol biosynthesis; lowers LDL by 35-60%

Question 8

Bile Acid Resins MOA

Answer 8

Bind to bile acids, preventing reabsorption and re-use of bile acid cholesterol; lowers LDL by up to 20%

Question 9

Ezetimibe MOA

Answer 9

prevents absorption of dietary cholesterol; lowers LDL by up to 20%

Question 10

Niacin MOA

Answer 10

Reduces VLDL synthesis; lowers LDL by up to 20%

Question 11

Common mechanisms of cholesterol lowering drugs

Answer 11

increase LDL receptor; promote uptake of LDL

Question 12

Lovastatin, Simvastatin

Answer 12

Inactive lactone prodrugs, lipid soluble, metabolized by CYP3A4, intermediate potency and efficacy

Question 13

Pravastatin

Answer 13

Water soluble, active open lactone ring, low potency/efficacy

Question 14

Atorvastatin, Rousuvastatin

Answer 14

Flourine containing congeners, active as given, long plasma half life, high potency/efficacy

Question 15

SREBP-2 role in statin therapy and cholesterol metabolism

Answer 15

protein that binds to SRE-1 which is a transcription factor that promotes up regulation of LDL receptors; promoted by statins by promoting ER to Golgi and cleavage of SREBP to increase number of LDL receptors

Question 16

Statins to use in patients with atherosclerotic vascular disease

Answer 16

High efficacy statins - Atorvastatin and Rosuvastatin

Question 17

Statins metabolized by CYP3A4

Answer 17

Simvastatin and Atorvastatin (also oxidization)

Question 18

Statins metabolized by sulfation

Answer 18

Pravastatin

Question 19

Statins metabolized by CYP2C9

Answer 19

Fluvastatin and Rosuvastatin

Question 20

Statins metabolized by UGT1A1

Answer 20

all statins undergo glucaronidation by UGT1A1

Question 21

Bile acid sequestrants

Answer 21

Colestipol (powder and tablet), Cholestyramine (powder), Colesevelam (tablet)

Question 22

Bile sequestrants drug interactions

Answer 22

prevents absorption of digoxin, beta blockers, thyroxine, coumadin

Question 23

Bile sequestrates contraindications

Answer 23

hypertriglyceridemia, complex drug regimens and critical medications, history of constipation (elderly)

Question 24

Ezetimibe

Answer 24

inhibits absorption of cholesterol by small intestine; no effect on fat soluble vitamins (ADEK); localizes to brush border of small intestinal epithelium; reduces delivery of cholesterol to liver; reduced hepatic cholesterol up regulates LDL receptors, increases clearance of LDL from plasma; distinct and complementary effect of statins

Question 25

Drugs that lower TGs and raise HDL-cholesterol

Answer 25

Fibric Acid Derivatives (Fibrates), Nicotinic Acid (niacin), omega 3 polyunsaturated fatty acids (fish oil)

Question 26

Fibric Acid Derivatives

Answer 26

Gemfibrozil and Fenofibrate MOA: ligand for activation fo PPARalpha nuclear receptor Reduces VLDL, increases HDL, TGs reduced, LDL unchanged SE: GERD, diarrhea, increased liver enzymes, increased creatinine, gallstones, Teratogenic

Question 27

Gemfibrozil

Answer 27

metabolized by liver (UGT1A1), reduces VLDL, TGs; increased HDL; can be used in pts with renal disease

Question 28

Fenofibrate

Answer 28

hepatic metabolsim, renal excretion so avoid in renal insufficiency

Question 29

Niacor

Answer 29

Immediate release nitrate which requires slow up-titration to minimize flushing

Question 30

Niaspan

Answer 30

Extended release - less flushing, better tolerated

Question 31

MOA of Nicotinic Acid

Answer 31

Niacin inhibits mobilization of FFA from adipocytes, reduced TG synthesis, ApoB, VLDL; increased HDL; promotes conversion of VLDL to LDL via enhanced Lipoprotein Lipase Reduction Lp(a) by 30% - unique feature

Question 32

Nicotinic Acid SE

Answer 32

cutaneous flushing (treat with aspirin), elevated transaminase, hepatitis, hepatic failure, GI irritation, hyperuricemia/gout, insulin resistance, pregnancy risk C

Question 33

Effects of Omega3s

Answer 33

reduce TGs and CV risk, also have anti platelet, anti arrhythmic, and BP lowering effect