7. Cholesterol

Question 1

What are the pro-atherogenic effects of Ox-LDL?

Answer 1

Inhibit macrophage motility, induce T cell activation, toxic to endothelial cells, enhances platelet aggregation.

Question 2

What are the classes of lipid lowering drugs?

Answer 2

Statins, cholesterol lipase inhibitors, nicotinic acid/niacin, fibrates, resins, omega-3 fatty acids.

Question 3

What is the action of statins?

Answer 3

Inhibit cholesterol synthesis in hepatocytes, increase clearance of IDL and LDL, decrease production of VLDL and LDL.

Question 4

What is the mechanism of action of statins?

Answer 4

Blocks HMG-CoA reductase, increases LDL receptor synthesis.

Question 5

What are the indications for use of statins?

Answer 5

CV risk prevention (CVD or diabetes), familial hypercholesterolaemia.

Question 6

What are some of the ADRs of statins?

Answer 6

Increased transaminase levels (reversible and no evidence of liver disease), myopathy (muscle pain and CPK high, usually in higher doses), GI complaints, arthralgia, headaches.

Question 7

What are some secondary benefits of statin treatment?

Answer 7

Anti-inflammatory, plaque reduction, improved endothelial cell function, reduced thrombotic risk.

Question 8

What are fibric acid derivatives? (Structure).

Answer 8

Amphipathic carboxylic acids.

Question 9

What receptors do fibric acid derivatives act on?

Answer 9

PPARa - peroxisome proliferator-activated receptor as an agonist.

Question 10

What is the action of fibric acid derivatives?

Answer 10

Increased production of lipoprotein lipase - reduced triglyceride production, improved postprandial triglyceridaemia.

Question 11

What is the mechanism of action of fibric acid derivatives?

Answer 11

Increased fatty acid uptake and oxidation, reduced TAGs levels, increased LDL size and HDL-C levels, vascular effects.

Question 12

What are the indications for fibric acid derivatives use?

Answer 12

Adjunctive therapy to diet, hypertriglyceridemia, combined hyperlipidemia with low HDL who don’t respond to nicotinic acid.

Question 13

How efficacious are fibric acid derivatives?

Answer 13

Decrease TAG 25-50%, LDL decreases but variable, increased HDL 15-25% in hypertriglyceridemia.

Question 14

What are some ADRs of fibric acid derivatives?

Answer 14

GI upset, cholelithiasis, myositis, abnormal LFTs.

Question 15

What are some contraindication for fibric acid derivative use?

Answer 15

Hepatic or renal dysfunction, pre-existing gallbladder disease.

Question 16

What are the effects of nicotinic acid?

Answer 16

Reduce VLDL and increase HDL (high dose).

Question 17

What is the mechanism of action of nicotinic acid?

Answer 17

Inhibits lipoprotein a synthesis and raises HDL-C.

Question 18

What are the ADRs of nicotinic acid?

Answer 18

Flushing, itching, headache, hepatotoxicity, GI upset, activation of peptic ulcer, hyperglycaemia and reduced insulin sensitivity.

Question 19

What are the contraindications of nicotinic acid use?

Answer 19

Active liver disease of LFT elevations, peptic ulcer disease.

Question 20

What is the mechanism of action of ezetimibe?

Answer 20

Selectively inhibits intestinal cholesterol absorption so decreased delivery to liver, more LDL receptors expressed and reduced cholesterol in atherogenic particles.

Question 21

What are the ADRs of ezetimibe?

Answer 21

Headache, abdominal pain, diarrhoea.

Question 22

What should be considered in combination therapy for cholesterol lowering drugs?

Answer 22

Benefit in terms of CV risk reduction, cost, and ADRs.

Question 23

What are the benefits of combining fibrates and statins as therapy to lower cholesterol?

Answer 23

Improve TAG, LDL-C, and HDL-C levels.

Question 24

What are the risks associated with combining fibrates and statins?

Answer 24

Myopathy and rhabdomyolysis.

Question 25

What are the positive additions to diet that may help cholesterol levels?

Answer 25

Fish oils, fibre, vitamin C/E, alcohol (increased HDL), plant sterols.

Question 26

What are the negative additions to diet that may worsen cholesterol levels?

Answer 26

Dietary cholesterol/fat, alcohol.