Lipid Lowering Drugs

Question 1

Lipoprotein lipase

Answer 1

Removes triglycerides in extrahepatic tissues

Question 2

Chylomicrons =

Answer 2

triglycerides + cholesterol

Question 3

4 major bile salts

Answer 3

Cholic acid
Chenodeoxycholic acid
Deoxycholic acid
Lithocholic acid

Question 4

Resin action

Answer 4

Bind bile acids through ionic and hydrophobic interactions –> block reabsorption of bile acids in the gut

Question 5

Cholestyramine =

Mechanism:

Adverse affect:

Answer 5

Bile acid sequestrant

1. Bind bile acids through ionic and hydrophobic interactions
2. Upregulation of LDL receptors
3. Increase hepatic production of VLDL

Dyspepsia, constipation, bloating, diarrhea
Malabsorption of vit. K
Impaired absorption of other drugs

Question 6

Colestipol =

Mechanism:

Adverse affect:

Answer 6

Bile acid sequestrant

1. Bind bile acids through ionic and hydrophobic interactions
2. Upregulation of LDL receptors
3. Increase hepatic production of VLDL

Dyspepsia, constipation, bloating, diarrhea
Malabsorption of vit. K
Impaired absorption of other drugs

Question 7

Colesevelam =

Mechanism:

Adverse affect:

Benefits:

Answer 7

Bile acid sequestrant

1. Bind bile acids through ionic and hydrophobic interactions
2. Upregulation of LDL receptors
3. Increase hepatic production of VLDL

Reduced side effect:
Dyspepsia, constipation, bloating, diarrhea
Malabsorption of vit. K

Does not bind digoxin, warfarin, reductase inhibitors

Question 8

Nicotinic acid (Niacin) =

Mechanism:

Adverse effect:

Answer 8

water soluble vitamin-incorporated into nicotinamide adenine dinucleotide (NAD)

Inhibits VLDL secretion –> decrease production of LDL
NO effect on bile production

1. Prostaglandin mediated cutaneous vasodilation: blunted w/ aspirin/NSAID
2. Reversible elevation in liver function tests
   Increase insulin resistance
3. Hyperuricemia: compete w/ uric acid for excretion by kidney

Question 9

Lovastatin =

Mechanism:

Adverse effect:

Answer 9

Competitively inhibit HMG CoA reductase
Pro-drug

1. Decrease cholesterol synthesis
2. Upregulate LDL receptors –> decrease LDL
3. First pass metabolism
4. Increased liver function test
5. Increased creatine kinase
6. Myopathy

Question 10

Simvastatin =

Mechanism:

Adverse effect:

Answer 10

Competitively inhibit HMG CoA reductase
Pro-drug

1. Decrease cholesterol synthesis
2. Upregulate LDL receptors –> decrease LDL
3. First pass metabolism
4. Increased liver function test
5. Increased creatine kinase
6. Myopathy

Question 11

Paravastatin =

Mechanism:

Adverse effect:

Answer 11

Competitively inhibit HMG CoA reductase
Active drug

1. Decrease cholesterol synthesis
2. Upregulate LDL receptors –> decrease LDL
3. First pass metabolism
4. Increased liver function test
5. Increased creatine kinase
6. Myopathy

Question 12

Fluvastatin =

Mechanism:

Adverse effect:

Answer 12

Competitively inhibit HMG CoA reductase
Active drug

1. Decrease cholesterol synthesis
2. Upregulate LDL receptors –> decrease LDL
3. First pass metabolism
4. Increased liver function test
5. Increased creatine kinase
6. Myopathy

Question 13

Lovastatin metabolized by:

Answer 13

CYP3A4

Question 14

Simvastatin metabolized by:

Answer 14

CYP3A4

Question 15

Atorvastatin metabolized by:

Answer 15

CYP3A4

Question 16

Fluvastatin metabolized by:

Answer 16

CYP2C9

Question 17

Rosuvastatin metabolized by:

Answer 17

CYP2C9

Question 18

Omega-3-fatty acids action:

Answer 18

activate PPARalpha –> decrease triglycerides

May decrease LDL

Question 19

Gemfibrozil =

Mechanism:

Use:

Toxicity:

Answer 19

Fibric acids = ligand for PPARalpha

1. Upregulate lipoprotein lipase, apo A1, apo AII –> HDL promote cholesterol efflux
2. Clears chylomicrons and VLDL
3. Lowers triglycerides and raises HDL

Hypertriglyceridemias (VLDL)

1. Rashes, GI symptoms, arrhythmia, low potassium, elevated liver function tests
2. Increased risk of myophathy –> increase blood concentration of statins by partially inhibiting metabolism
3. Increased cholesterol gallstones

Question 20

Clofibrate =

Mechanism:

Use:

Toxicity:

Answer 20

Fibric acids = ligand for PPARalpha

1. Upregulate lipoprotein lipase, apo A1, apo AII –> HDL promote cholesterol efflux
2. Clears chylomicrons and VLDL
3. Lowers triglycerides and raises HDL

Hypertriglyceridemias (VLDL)

1. Rashes, GI symptoms, arrhythmia, low potassium, elevated liver function tests
2. Increased cholesterol gallstones

Question 21

Fenofibrate =

Mechanism:

Use:

Toxicity:

Answer 21

Fibric acids = ligand for PPARalpha

1. Upregulate lipoprotein lipase, apo A1, apo AII –> HDL promote cholesterol efflux
2. Clears chylomicrons and VLDL
3. Lowers triglycerides and raises HDL

Hypertriglyceridemias (VLDL)

1. Rashes, GI symptoms, arrhythmia, low potassium, elevated liver function tests
2. Increased cholesterol gallstones
   * * minimal effect on pharmacokinetics of statins

Question 22

Ezetimibe =

Answer 22

inhibit NPC1L1 –> inhibit intestinal sterol absorption

**not a CYP450 substrate

Question 23

Drug therapy for: High LDL-cholesterol

Answer 23

1. bile acid sequestrant
2. Nicotinic acid or HMG CoA reductase inhibitor
3. combo of 1 and 2

Question 24

Drug therapy for: High LDL and triglycerides

Answer 24

1. Weight loss, alcohol restriction
2. Nicotinic acid or gemfibrozil
3. Bile acid sequestrants or HMG CoA reductase inhibitors in combo 1 or 2
4. Combo of any 2 of: nicotinic acid, gemfibrozil, HMG CoA reductase inhibitors –> increase risk of toxicity

Question 25

Drug therapy for: High triglycerides, NORMAL LDL

Answer 25

1. Weight loss, alcohol restriction | 2. Genfibrozil or nicotinic acid

Question 26

Drug therapy for: low HDL

Answer 26

1. Diet, exercise, stop smoking | 2. Nicotinic acid or gemfibrozil