Lipid lowering

Question 1

What is the exogenous pathway for lipoprotein transport in blood?

Answer 1

Cholesterol and TAGs from GIT enter intestinal lymph, transported to blood as chylomicrons, are hydrolysed at the cell periphery.

Question 2

What is the endogenous pathway for lipoprotein transport in blood?

Answer 2

Cholesterol and TAGs from liver are transported as VLDL to muscle/adipose to be hydrolysed and lipoproteins become LDL

Question 3

List the different types of lipid-lowering agents.

Answer 3

Statins, fibrates, inhibitors of cholesterol absorption (resins, ezetimibe), nicotinic acid, fish oil.

Question 4

What is the mechanism of action of statins?

Answer 4

Competitively inhibit HMG CoA reductase to block cholesterol synthesis in the liver
Reduce cholesterol in the liver, increases expression of LDL receptors, increasing uptake by hepatocytes and clearance.
Improve endothelial function, stabilise plaques.

Question 5

What is the effect of statins on lipoproteins?

Answer 5

Lower LDL substantially, lower TGs and raise HDL.

Question 6

What are the indications for statins?

Answer 6

Hypercholesterolaemia, high risk CHD, secondary prevention of MI and stroke

Question 7

What are the side effects of statins?

Answer 7

GI disturbances, insomnia, rash, myopathic effects - muscle breakdown, pain, enzyme changes

Question 8

What are the clinical considerations for statins?

Answer 8

Avoid in pregnancy, memory loss in diabetes.

Question 9

What is the mode of action of fibrates?

Answer 9

Peroxisome proliferator-activated receptor alpha (PPAR) agonists
Stimulate lipoprotein lipase
Decrease hepatic VLDL production, increase hepatic LDL uptake

Question 10

What is the peroxisome proliferator-activated receptor alpha (PPAR)?

Answer 10

Nuclear receptor that influences metabolism in the liver, adipose, muscle and heart.

Question 11

What is lipoprotein lipase?

Answer 11

Converts triglycerides into free fatty acids and glycerol to increase lipid availability for muscle.

Question 12

What are the indications for lipoproteins?

Answer 12

Reduce LDL, substantially reduce TGs and increase HDL.

Question 13

What are the indications for fibrates?

Answer 13

Hypertriglyceridaemia, mixed hyerlipidaemia

Question 14

What are the side effects of fibrates?

Answer 14

GI disturbances

Question 15

Give example of cholesterol absorption inhibitors.

Answer 15

Bile acid binding resins

Ezetimibe

Question 16

What is the mechanism of action of resins?

Answer 16

Bind with bile acids, reducing absorption of exogenous cholesterol.
Increase metabolism of endogenous cholesterol, reduce intracellular cholesterol in hepatocytes.
There is a compensatory increase in LDL receptors.

Question 17

What are the indications for resins?

Answer 17

Hypercholesterolaemia, mixed hyperlipidaemia.

Question 18

What are the side effects of resins?

Answer 18

GI discomfort

Question 19

What is the mechanism of action of Ezetimibe?

Answer 19

Inhibits cholesterol absorption across the intestinal wall - blocks transport protein NPC1L1 in brush border
Does not stop absorption of fat-soluble vitamins

Question 20

How is ezetimibe used?

Answer 20

Adjunct to statin

Question 21

What is the benefit of ezetimibe of resins?

Answer 21

Better tolerance, higher potency.

Question 22

What is the mechanism of action of nicotinic acid?

Answer 22

Inhibit VLDV secretion from liver, decreases Lp(a) (Lp(a) promotes thrombosis)
Lowers LDL, TG and raises HDL

Question 23

What are the benefits of omega-3 polyunsaturated fatty acids (PUFA)?

Answer 23

Substitution of PGI2 and TXA2 with PGI3 and TXA3, which are more favourable.

Question 24

Which drugs are used for hypercholesterolemia?

Answer 24

Statins, resins, nicotinic acid, ezetimibe and fibrates.

Question 25

Which drugs are used for hypertriglyceridemia?

Answer 25

Fibrates, nicotinic acid, fish oils.