4.1 pharm plasma

Question 0

LDL

• apolipoprotein
• receptor

Answer 0

ApoB100

LDL receptor in liver & peripheral tissues

Question 1

Chylomicron remnant

• apolipoprotein
• receptor

Answer 1

ApoE

LPR receptor in liver

Question 2

HDL

• apolipoprotein
• receptor

Answer 2

ApoAI& ApoAII

SRB1 receptor in liver

Question 3

Enzyme that acts on chylomicrons and VLDL

Answer 3

Lipoprotein lipase

Question 4

What does lipoprotein lipase cleave off

Answer 4

Free fatty acids

Question 5

Type IA hyperlipidemia

Answer 5

Familial hyperchylomicronemia: deficiency of lipoprotein lipase

Question 6

Type IIA hyperlipidemia

Answer 6

Familial hypercholesterolemia: autosomal dominant defect in LDL receptor gene

Question 7

Type IIB hyperlipidemia

Answer 7

Familial combined hyperlipidemia: Increased LDL and triglycerides, often decreased HDL
Mutations in apolipoproteins and enzymes of lipoprotein metabolism

Question 8

Type III hyperlipidemia

Answer 8

Familial dysbetalipoproteinemia: Deficiency in apolipoprotein E
Increased LDL, triglyceride, cholesterol levels, decreased HDL

Question 9

Type IV hyperlipidemia

Answer 9

Familial hypertriglyceridemia: autosomal dominant, increased triglycerides but not cholesterol

Question 10

Type V hyperlipidemia

Answer 10

Increased triglycerides, slightly increased cholesterol

Question 11

Why high levels of LDL increases atherosclerosis

Answer 11

LDL becomes oxidized in endothelial space. Oxidized LDL is ingested by macrophages, which forms foam cells. Dead foam cells make lipid rich core in atherosclerotic plaques

Question 12

MOA of statins

Answer 12

Inhibits HMG CoA reductase

Question 13

Major use if cholesterol in liver

Answer 13

Make bile acids

Question 14

How stains decrease plasma cholesterol

Answer 14

Need cholesterol to make bile acids - got rid of body’s way of making cholesterol, so up regulate uptake of LDL from plasma by increasing LDL receptors

Question 15

When do you discontinue statin therapy

Answer 15

When ALT AST are >3x normal levels

Question 16

What statins are not associate with increased LFTs

Answer 16

Pravastatin
Lovastatin
Simvastatin

Question 17

Diagnose rhabdomyolysis

Answer 17

Myalgia or muscle weakness with elevated CPK

Question 18

Rhabdomyolysis can lead to

Answer 18

Acute renal failure or death

Question 19

Main lipid change of statins

Answer 19

Decreased LDL

Question 20

Statin CI

Answer 20

Absolute:
Active or chronic liver disease
Pregnant / nursing mothers

Relative:
3A4

Question 21

Which statin is not metabolized by CYP

Answer 21

Pravastatin

Question 22

Bile acid binding resins / sequestrant MOA

Answer 22

Binds negatively charged bile acids in intestine so can’t be reabsorbed

Question 23

Lipid change of bile acid binding resins

Answer 23

Decrease LDL

No change / increase TGs

Question 24

Side effects of bile acid binding resins

Answer 24

Taste bad GI (abd pain, bloating, constipation, diarrhea) Gallstones (incr conc chol in bile)

Question 25

Bile acid binding resin CI

Answer 25

Absolute: Dysbetalipoproteinemia TAGs > 400 mg Relative: TAGs >200

Question 26

Cholesterol absorption blocker MOA

Answer 26

Inhibits dietary and biliary cholesterol uptake from intestinal lumen Reduces cholesterol transport at brush border membrane by targeting NPC1L1

Question 27

Main lipid change for cholesterol absorption blockers

Answer 27

Decrease LDL

Question 28

Example of cholesterol absorption blocker

Answer 28

Ezetimibe

Question 29

Side effects of cholesterol absorption blockers

Answer 29

Rare allergy Rare LFTs Myopathy (more common if combo with statin)

Question 30

Niacin MOA

Answer 30

Decrease TAG breakdown in adipose tissue, so decrease FFA into plasma and therefore liver, which reduces TAG and VLDL production

Question 31

Main lipid change for niacin

Answer 31

Increase HDL

Question 32

Side effects of niacin

Answer 32

Flushing reaction Hepatotoxicity Hyperglycemia Hyperuricemia (exacerbates gout)

Question 33

Niacin CI

Answer 33

Abs: Chronic liver disease Severe gout Pregnancy Relative: Diabetes Peptic ulcer

Question 34

New studies on bad effects of niacin

Answer 34

``` Strokes Diabetes Infection Bleeding Hemorrhagic strokes ```

Question 35

Fibric acid derivative MOA

Answer 35

Activate PPARα which activates genes in lipoprotein metabolism - incr LPL activity (decreased TAG) - modulate apolipoprotein levels (incr clearance of TAG rich particles) - decreased TAG synthesis

Question 36

Main lipid change of fibric acid derivatives

Answer 36

TAG decrease

Question 37

Fibrate side effects

Answer 37

LFTs Nausea Gallstones

Question 38

Fibrate CI

Answer 38

Abs: Severe renal or hepatic disease Pregnancy Childhood use