Lipid Lowering Drugs

Question 1

MOA of Niacin (nicotinic acid, vitamin B3)

Answer 1

1. Strongly inhibits lipolysis in adipose tissue → both plasma triacylglycerol (in VLDL) and cholesterol (in VLDL and LDL) are lowered
2. Increases HDL-cholesterol levels
3. By decreasing circulating fibrinogen and increasing tissue plasminogen activator → reverse thrombosis associated with hypercholesterolemia and atherosclerosis

Question 2

Clinical uses of Niacin (nicotinic acid, vitamin B3)

Answer 2

Widely used, especially for the treatment of Type IIb and IV hyperlipoproteinemia

Question 3

PK of Niacin (nicotinic acid, vitamin B3)

Answer 3

oral, it is converted in the body to nicotinamide

Question 4

Adverse effects of Niacin (nicotinic acid, vitamin B3)

Answer 4

1. an intense cutaneous flush and pruritus

2. hyperuricemia and gout

Question 5

Examples of fibrates / fibric acid derivatives

Answer 5

1. gemfibrozil
2. fenofibrate
3. clofibrate

Question 6

MOA of fibrates / fibric acid derivatives

Answer 6

1. they are ligands for peroxisome proliferators-activated receptor-alpha (PPAR-alpha) protein, the interaction with PPAR-alpha results in increased activity of lipoprotein lipase
2. by stimulating lipoprotein lipase activity, they cause a decrease in plasma triacyglycerol levels
3. levels of VLDL decrease in part as a result of decreased secretion by the liver
4. HDL levels rise moderately

Question 7

Clinical uses of fibrates/fibric acid derivatives

Answer 7

treatment of hypertriglyceridemias with VLDL elevation, especially for dysbetalipoproteinemia

Question 8

Adverse effects of fibrates/fibric acid derivatives

Answer 8

1. GI effects: Nausea
2. Skin rashes
3. Gall-stones
4. Myositis

Question 9

Examples of bile acid binding resins

Answer 9

1. Colestipol

2. Cholestryamine

Question 10

MOA of bile acid binding resins

Answer 10

1. anion exchange resins bind negatively charged bile acids and bile salts in the small intestine
2. lowering the bile acid concentration causes hepatocytes to increase conversion of cholesterol to bile acids, thus intracellular cholesterol concentration decreases
3. activates an increased hepatic uptake of cholesterol-containing LDL particles, leading to a fall in plasma LDL
4. may increase VLDL, but have little effect on HDL

Question 11

Clinical uses of bile acid binding resins

Answer 11

1. treatment of patients with primary hypercholesterolemia (IIa)
2. • niacin: treat LDL elevations in persons with combined hyperlipidemia (IIb)

Question 12

PK of bile acid binding resins

Answer 12

Oral only

Question 13

Adverse effects of bile acid binding resins

Answer 13

1. GI effects: constipation, nausea, flatulence

2. Impaired absorptions: Vitamins A,D,E & K

Question 14

Examples of HMG-CoA reductase inhibitors

Answer 14

1. Atorvastatin
2. Simvastatin
3. Pravastatin
4. Fluvastatin

Question 15

MOA of HMG-CoA reductase inhibitors

Answer 15

1. Inhibition of HMG-CoA reductase: their strong affinity for the enzyme compete effectively to inhibit HMG-CoA reductase, the rate limiting step in cholesterol synthesis
2. upregulates LDL receptors on cell surface: depletion of intracellular cholesterol causes the cell to increase the number of specific cell-surface LDL receptors that can bind and internalise the circulation of LDLs

Question 16

Clinical use of HMG-CoA reductase inhibitors

Answer 16

1. Effective in lowering plasma cholesterol levels in all types of hyperlipidemias
2. Reduce the risk of coronary events and mortality in patients with ischemic heart disease

Question 17

PK of HMG-CoA reductase inhibitors

Answer 17

1. Oral, first pass extraction

2. Given in the evening

Question 18

Adverse effects of HMG-CoA reductase inhibitors

Answer 18

1. liver: biomedical abnormalities in liver function

2. muscle: myopathy and rhabdomyolysis

Question 19

Contraindication of HMG-CoA reductase inhibitors

Answer 19

1. pregnancy
2. nursing mothers
3. children
4. teenagers

Question 20

Example of inhibitors of intestinal sterol absorption

Answer 20

ezetimibe

Vytorin: ezetimibe + simvastatin

Question 21

MOA of inhibitors of intestinal sterol absorption

Answer 21

selective inhibitor of cholesterol transport protein, NPC1L1

Question 22

Clinical uses of inhibitors of intestinal sterol absorption

Answer 22

reduction of LDL

Question 23

PK of inhibitors of intestinal sterol absorption

Answer 23

readily absorbed, conjugated in the intestinal wall to an active glucuronide

Question 24

Adverse effect of inhibitors of intestinal sterol absorption

Answer 24

low incidence of reversible impaired hepatic function