Lipid Lowering Drugs (Antilipemic drugs) - Ch. 53

Question 1

What are the 2 primary forms of lipids in blood?

Answer 1

Tryglycerides (TGs)
Cholesterol

-Water-insoluble fats
-Must be packaged for transport in blood

Question 2

What are Lipoproteins?

Answer 2

Combination of lipids with proteins

Question 3

What are some examples of Lipoproteins?

Answer 3

Chylomicrons
Very-low density lipoprotein (VLDL)
Low-density lipoprotein (LDL)
High-density lipoprotein (HDL)

Question 4

Where are chylomicrons produced?

Answer 4

GI tract

Question 5

Where are Very-low density lipoprotein (VLDL) produced?

Answer 5

Liver

Question 6

What do Very-low density lipoprotein (VLDL) do?

Answer 6

Transport triglycerides to cells

Question 7

What is LDL?

Answer 7

“Less desired”, “bad cholesterol”
-Cholesterol rich

Question 8

What is LDL used for?

Answer 8

-Binds to receptors on cell membranes
-Cholesterol source during production of steroid hormones

Question 9

What is HDL?

Answer 9

“highly desired” “good cholesterol”
-prevents cholesterol from building up in vessels

Question 10

What does HDL do?

Answer 10

Absorbs cholesterol and transports it to the liver where it is recycled

Question 11

What are some non-modifiable factors leading to coronary artery disease?

Answer 11

Age
-Male 45 years or older
-Female 55 years or older, or postmenopausal

Family history
-strong history of premature Congenital heart disease

Question 12

What are some modifiable factors leading to coronary artery disease?

Answer 12

Current cigarette smoker
Abdominal obesity
Hypertension (BP- 140/90 or higher, or on antihypertensive drugs)
Diabetes mellitus
LDL/HDL ration

Question 13

What are the 4 groups of lipid lowering drugs?

Answer 13

1. HMG-CoA reductase inhibitors (HMGs, or statins)
2. Inhibitors of Cholesterol Absorption
3. Niacin (nicotinic acid)
4. Fibric acid derivatives

Question 14

What is HMG-CoA?

Answer 14

3-Hydroxy-3-methylglutaryl coenzyme A

One of age metabolites in the cholesterol synthesis pathway

Question 15

What is HMG-CoA reductase?

Answer 15

Critical enzyme for liver cholesterol production

Question 16

What do HMG-CoA reductase inhibitors do?

Answer 16

Reduce plasma LDL levels

Question 17

Examples of HMG-CoA reductase inhibitors?

Answer 17

Atorvastatin (lipitor)
Rosuvastatin (Crestor) -possibly less AE
Lovastatin (Mevacor)
Simvastatin (Zocor)

Question 18

What is the mechanism of action of HMG-CoA reductase inhibitors?

Answer 18

Inhibit HMG-CoA reductase
Lower rate of cholesterol production

Question 19

Because HMG-CoA reductase inhibitors lower the rate of cholesterol production what happens?

Answer 19

Increased liver LDL receptors which increases plasma clearance of LDL

Question 20

What are the added benefits of Statins/HMG-CoA reductase inhibitors?

Answer 20

Decrease VLDL (major carriers of TGs)
Raise HDL
-improves LDL/HDL ratio

Question 21

What are HMG-CoA reductase inhibitors used for?

Answer 21

First-line drug therapy for hypercholesterolemia
Treatment of types of II and IIb hyperlipidemias
-high LDL levels

Question 22

What adverse effects are associated with HMG-CoA reductase inhibitors?

Answer 22

Mild, transient GI disturbances
headache
Muscle pain (myalgia)
Rhabdomyolysis (rarer)
Liver injury (increased liver enzymes)

Question 23

When is HMG-CoA reductase inhibitors use contraindicated?

Answer 23

Preganancy
Use with caution with liver dysfunction patients e.g, viral hepatitis

Question 24

What racial group should have a lower dose of rosuvastatin?

Answer 24

Asians

Question 25

What can some HMG-CoA reductase inhibitors interact with that isn't a drug?

Answer 25

Grapefruit juice -Causes CYP3A4 inhibition

Question 26

What HMG-CoA reductase inhibitors interact with grapefruit juice?

Answer 26

Lovastatin simvastatin atorvastatin

Question 27

What drugs do HMG-CoA reductase inhibitors interact with?

Answer 27

Drug inhibitors of CYP3A4 -warfarin (oral anticoagulant) -erythromycin (macrolide antibacterial) -ritonavir (HIV protease inhibitor)

Question 28

What are some drugs that inhibit cholesterol absorption/

Answer 28

Bile acid-binding resins Ezetimibe

Question 29

Examples of Bile acid-binding resins (bile acid sequestrants)?

Answer 29

Cholestyraminde Colestipol

Question 30

What is the mechanism of action of bile acid sequestrants?

Answer 30

Prevent reabsorption of bile acids from small intestine -bile acids are synthesised from cholesterol in the liver -liver stimulated to produce more bile acids

Question 31

What are bile acid sequestrants used for?

Answer 31

***Type II hyperlipoproteinemia*** relief of Pruritus associated with partial biliary obstruction (cholestyramine)

Question 32

What adverse effects are associated with bile acid sequestrants?

Answer 32

GI disturbances : constipation, heartburn, nausea, belching, bloating (tend to disappear over time) **Decrease absorption of fat soluble vitamins A, D, E,K**

Question 33

What are fibric acid derivatives (fibrates) mechanism of action?

Answer 33

complex -Believed to work by activating lipoprotein lipase (which breaks down TGs in lipoproteins) -Reduces plasma TGs -Increase fatty acid use in tissues

Question 34

What do fibric acid derivatives (fibrates) do?

Answer 34

Decrease plasma triglyceride levels Increase HDL bias much as 10-25%

Question 35

Examples of fibric acid derivatives (fibrates)?

Answer 35

gemfibrozil bezafibrate (Bezalip) fenofibrate (Lipidil)

Question 36

What adverse effects are associated with fibric acid derivatives (fibrates)?

Answer 36

GI disturbances : abdominal discomfort, diarrhoea, nausea Blurred vision Increased risk of gallstones Prolonged prothrombin time (fibrinogen production reduces, displacement of anticoagulants from albumin)

Question 37

What is Nicotinic Acid (Niacin)?

Answer 37

Vitamin B3

Question 38

What does Nicotinic acid (Niacin) do?

Answer 38

Reduce plasma TGs

Question 39

What is required dosing wise when Niacin is given for its lipid lowering properties rather than just as a vitamin?

Answer 39

Needs a much higher dose (grams)

Question 40

Why is Niacin used?

Answer 40

Effective and inexpensive -often in combination with the lipid-lowering agents e.g, statins

Question 41

What is the mechanisms of action of niacin?

Answer 41

Reduces VLDL (TGs carrier) from liver -Inhibits lipase in adipose tissue (breaks down lipids) -less fatty acids for TG production in liver

Question 42

What adverse effects are associated with Niacin/ Nicotinic acid?

Answer 42

Flushing (PG release) Pruritis (anal itchiness) GI distress

Question 43

How is flushing caused by nicotinicn acid (niacin) prevented?

Answer 43

take Aspirin 30 minutes before