Drugs Used in Atherosclerosis

Question 1

Cholestyramine

1) Mechanism of Action
2) Use
3) Side effects

Answer 1

1) Bile acid sequestrant - bind to bile acids and prevent reabsorption. Lower cholesterol by using it to make new bile acids.
2) Hyperlipidemia
3) GI effects, malabsorption vitamin K, impaired absorption of other drugs

Question 2

Colesevelam

1) Mechanism of Action
2) Use

Answer 2

1) Next generation bile acid sequestrant - bind to bile acids and prevent reabsorption. Lower cholesterol by using it to make new bile acids.
2) Hyperlipidemia

Question 3

Nicotinic Acid (Niacin)

1) Mechanism of Action
2) Use
3) Side effects

Answer 3

1) Inhibits VLDL secretion therefor decreasing production of LDL; Decreases triglycerides > cholesterol
2) Hyperlipidemia
3) Flush due to prostaglandin mediated cutaneous vasodilation, reversible elevations in LFT, hyperuricemia

Question 4

Lovastatin

1) Mechanism of Action
2) Use
3) Side effects

Answer 4

1) Prodrug of HMG CoA reductase inhibitors–> decrease cholesterol synthesis AND up regulate LDL receptors and decrease LDL
2) Hyperlipidemia, hypercholesterolemia
3) Increase LFT, CK, myopathies, major drug-drug interactions due to CYPs
* *Levels of drug elevated when drinking grapefruit juice (inhibits CYPs)

Question 5

Pravastatin

1) Mechanism of Action
2) Use
3) Side effects

Answer 5

1) Active form of a HMG CoA reductase inhibitors–> decrease cholesterol synthesis AND up regulate LDL receptors and decrease LDL
2) Hyperlipidemia, hypercholesterolemia
3) Increase LFT, CK, myopathies, major drug-drug interactions due to CYPs
* *Levels of drug elevated when drinking grapefruit juice (inhibits CYPs)

Question 6

Simvastatin

1) Mechanism of Action
2) Use
3) Side effects

Answer 6

1) Prodrug of HMG CoA reductase inhibitors–> decrease cholesterol synthesis AND up regulate LDL receptors and decrease LDL
2) Hyperlipidemia, hypercholesterolemia
3) Increase LFT, CK, myopathies, major drug-drug interactions due to CYPs
* *Levels of drug elevated when drinking grapefruit juice (inhibits CYPs)

Question 7

Fluvastatin

1) Mechanism of Action
2) Use
3) Side effects

Answer 7

1) Active form of a HMG CoA reductase inhibitors–> decrease cholesterol synthesis AND up regulate LDL receptors and decrease LDL
2) Hyperlipidemia, hypercholesterolemia
3) Increase LFT, CK, myopathies, major drug-drug interactions due to CYPs
* *Levels of drug elevated when drinking grapefruit juice (inhibits CYPs)

Question 8

Alirocumab

1) Mechanism of Action
2) Use

Answer 8

1) Monoclonal antibodies that bind and inhibit the enzyme Proprotein converts subtilisin/kexin type 9 (PCSK9)–> increases number of LDL receptors on the surface of the liver which increases LDL clearance
2) Hyperlipidemia

Question 9

Evolocumab

1) Mechanism of Action
2) Use

Answer 9

1) Monoclonal antibodies that bind and inhibit the enzyme Proprotein converts subtilisin/kexin type 9 (PCSK9)–> increases number of LDL receptors on the surface of the liver which increases LDL clearance
2) Hyperlipidemia

Question 10

Gemfibrozil

1) Mechanism of Action
2) Use
3) Side effects

Answer 10

1) Ligands of PPARa –> up regulates lipoprotein lipase, apo A-I, apo A-II (major components of HDL) –> promote cholesterol efflux
2) Hypertriglycerides (VLDL)
3) Risk of myopathy when used with statins

Question 11

Clofibrate

1) Mechanism of Action
2) Use

Answer 11

1) Ligands of PPARa –> up regulates lipoprotein lipase, apo A-I, apo A-II (major components of HDL) –> promote cholesterol efflux
2) Hypertriglycerides (VLDL)

Question 12

Fenofibrate

1) Mechanism of Action
2) Use

Answer 12

1) Ligands of PPARa –> up regulates lipoprotein lipase, apo A-I, apo A-II (major components of HDL) –> promote cholesterol efflux
2) Hypertriglycerides (VLDL)
* *Minimal effect on pharmacokinetics of statins

Question 13

Ezetimibe

1) Mechanism of Action
2) Use

Answer 13

1) Impairs intestinal absorption of cholesterol by inhibiting NPC1L1
2) Hyperlipidemia

Question 14

VLDL Metabolism: Endogenous Pathway

Answer 14

• Synthesized and secreted by the liver

- Converted to LDL by further removal of triglycerides (hepatic lipase)

Question 15

LDL Metabolism: Endogenous Pathway

Answer 15

• Can be internalized by hepatic and non hepatic tissues –> hepatic LDL is converted to bile acids and secreted into intestinal lumen
• Circulating LDL can enter tissues –> foam cells –> atheromatous plaques

Question 16

HDL Metabolism: Endogenous Pathway

Answer 16

-Takes up extra cholesterol and “removes” LDL

Question 17

Exogenous Pathway of Lipid Metabolism

Answer 17

1: Intestinal absorption
2: In intestinal cell fatty acids combine with glycerol –> triglycerides; Cholesterol esterfied –> combine with triglycerides into chylomicrons (lipoproteins)
3: Chylomicrons enter circulation
4: Lipoprotein lipase removes triglycerides in skeletal muscle and adipose
5: Chylomicron remnants take up by hepatocytes

Question 18

Cholesterol

Answer 18

Component of animal cell membranes: comes from dietary sources and 25% of production occurs in the liver

Question 19

Cholesterol biosynthetic pathway

Answer 19

Acetyl CoA –> HMG CoA –HMG CoA Reductase –> Mevalonic acid ….. –> cholesterol

Question 20

Triglycerides

Answer 20

Glycerol + 3 fatty acids

Store and circulate fat

Question 21

Lipoproteins

Answer 21

Complex of lipids and proteins –> enable transport of lipids