Chapter 17 Lipid-Regulating Drugs

Front 1

Why do we use lipid lowering drugs?

Back 1

Increased Serum lipid plays a role in the pathogenesis of atherosclerosis.

Front 2

What are the 4 common types of Lipid lowering drugs?

Back 2

HMG CoA reductase inhibitors (statins); bile acid binding agents; niacin; fibrates

Front 3

What is the mechanism of the most effective type of lipid lowering drug, i.e. statins?

Back 3

Competitive inhibition of HMG CoA reductase in the liver, which rate limits cholesterol synthesis

Front 4

Name the 3 mechanism by which serum LDL falls in response to statins.

Back 4

1. increased LDLR expression;
2. increased clearance of LDL precursors (e.g. VLDL) via LDLR;
3. VLDL production falls due to decreased cholesterol(therefore less will form LDL)

Front 5

Describe Statins effect on HDL, LDL, & TG.

Back 5

HDL increase; LDL & TG decrease

Front 6

True/False - LDL reduction promotes plaque stability and therefore decreases risk of thrombus formation.

Back 6

True

Front 7

True/False - Statins improve plaque stability by inhibiting monocyte penetration and increasing macrophage metalloproteinase secrection.

Back 7

False - Statins improve plaque stability by inhibiting monocyte penetration and decreasing macrophage metalloproteinase secrection.

Front 8

Statins are often used to treat CAD. What are the side effects for these drugs?

Back 8

Side effects: GI upset, Sleep disturbance, rare hepatoxicity & myotoxicity;

Front 9

What are the contraindications for statins?

Back 9

Drugs that inhibit isoform 3A4 Cytochrome P450.

Front 10

Describe the mechanism of Lipid Reduction in Bile Acid Binding Agents.

Back 10

These drugs bind/make polar bile acids thereby preventing reabsorption. This excretion causes the body to use cholesterol to make more Bile Acids.

Front 11

True/False - Unlike Statins, Bile Acid Binding Agents MAY increase serum TG levels.

Back 11

True - Bile Acid Binding Agents may increase cholesterol synthesis leading to increased VLDL.

Front 12

Give examples of Bile Acid Binding Agents.

Back 12

resins - cholestyramine, colestipol; hydrophilic polymer - colesevelam

Front 13

As a second line drug, Bile Acid Binding Agents have what side effects?

Back 13

bloating, constipation, nausea

Front 14

Bile Acid Binding Agents are contraindicated in what circumstances?

Back 14

interferes with certain drug absorptions (e.g. TH, propanolol, digoxin, warfarin)

Front 15

Describe Bile Acid binding Agents effect on HDL, LDL, & TG.

Back 15

HDL increase; LDL decrease; MAY increase TG

Front 16

Describe Niacin's effect on HDL, LDL, & TG.

Back 16

HDL increase; LDL & TG decrease

Front 17

Which of the lipid lowering drugs reduce lipoprotein a levels and is most effective at increasing HDL?

Back 17

Niacins

Front 18

What are the 4 mechanisms by which niacins work?

Back 18

1. inhibits FA release from fat which is necessary for TG synthesis ;
2. enhanced lipoprotein lipase action on circulating VLDL leads to TG clearance;
(1/2 low TG = low VLDL = low LDL);
3. reduces proportion of small, dense LDL for larger forms;
4. increased HDL via reduced uptake of its Apoprotein A1

Front 19

What are the side effects of Niacin?

Back 19

Transient cutaneous flushing, GI upset, hepatoxicity, myotoxicity?

Front 20

In what 3 groups of people should Niacins be used cautiously?

Back 20

reactivation of gout; excaberation of peptic ulcer disease; induced insulin resistance in diabetics

Front 21

Give examples of fibrates, which are lipid lowering drugs most effective at lowering Tg's.

Back 21

Gemfibrozil, Fenofibrate

Front 22

Describe the effects of Fibrates on LDL, HDL, and Tg.

Back 22

LDL variable!; Increase HDL; lower TG

Front 23

Describe the mechanism of action of Fibrates.

Back 23

THOUGHT to activate PPAR-alpha which:
a. lowers TG via FA oxidation and increased Lipoprotein lipase activity;
b. increase HDL via increased AI and AII

Front 24

True/False - Fibrates are absolutely contraindicated in liver or kidney dysfunction.

Back 24

False - Fibrates are glucornoidated and excreted via the kidneys but can be used cautiously.

Front 25

Name the common side effects of Fibrates.

Back 25

Dyspepsia, gallstones, myalgias

Front 26

Name the 3 drug interactions that must be considered before concomitantly prescribing a Fibrates.

Back 26

1. risk of increased rhabdomyolysis with statins;
2. increased anticoagulation with warfarin;
3. increased potency of oral hypoglycemics drugs