Anti-hyperlipidaemics - Fibrates Flashcards
Cholesterol is often judged as being all bad. However, there are a number of benefits of cholesterol. Which of the following is NOT one of these benefits?
1 - part of lipid membranes
2 - component of bile
3 - synthesise coagulation factors
4 - steroid synthesis
5 - vitamin D
3 - synthesise coagulation factors
- we need cholesterol in our skins cells to make vitamin D from sunlight.
Once lipids and cholesterol have been packaged into chylomicrons, do they enter the circulatory system or lymphatics?
- lymphatics
- they then enter the circulation at the subclavian vein
- they can then travel to the liver and adipose tissue
The liver is able to synthesis cholesterol, or we can consume it in out diets. Once fats and cholesterol have been digested and absorbed they are transported around the body in lipoproteins (contain phospholipids and proteins tags) as they are hydrophobic. What is the 1st lipoprotein they are packaged in?
1 - chylomicrons
2 - LDL
3 - HDL
4 - VLDL
1 - chylomicrons
- largest lipoprotein
- least dense lipoprotein (essentially they are large and not full, so not dense)
Once cholesterol has been synthesised in the liver, it is once again packed up into lipoproteins and sent off into the circulation to carry TAGs to the rest of the body. Which type of lipoprotein is used 1st?
1 - chylomicrons
2 - LDL
3 - HDL
4 - VLDL
4 - VLDL
- low density refers to the concentration of cholesterol
- VLDL = high TAGs and low cholesterol
- LDL = low TAGs and high cholesterol
The liver is able to synthesis cholesterol using the mevalonate pathway. What is the rate limiting step in this pathway, that ultimately determines cholesterol synthesis?
1 - fatty acid synthase
2 - 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase
3 - HMG-CoA synthase
4 - acetyl-coA carboxylase
2 - 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase
- this enzyme creates mevalonate, which is the precursor of cholesterol
Once VLDL have been distributed around the body and distributed TAGs they become LDLs (distribute cholesterol around the body), and ultimately HDLs. What is the benefit of HDLs?
1 - remove excess TAGs from blood
2 - collect excess cholesterol and return it to the liver
3 - remove cholesterol from plaques
4 - distribute cholesterol around the body
2 - collect excess cholesterol and return it to the liver
If these is a lot of LDL, the tissues taking up the cholesterol become saturated. What is a key risk of this in the endothelium of blood vessels?
1 - cause vasodilation
2 - cause damage to endothelium and initiate the coagulation cascade
3 - collect on endothelium and form plaques
4 - all of the above
3 - collect on endothelium and form plaques
- increase risk of strokes, MI and PVD
Once VLDL are released into the circulation they deliver TAGs to the tissues in the body. What enzyme is present in the endothelium that allows them to extract TAGs and breaks them down into fatty acids. What is this enzyme called?
1 - lipoprotein lipase
2 - pancreatic lipase
3 - hepatic lipase
4 - endothelium lipase
1 - lipoprotein lipase
- fatty acids can be used for energy
- adipose cells convert fatty acids back into TAG for energy storage
Which 2 of the following can be caused by hypertriglyceridemia?
1 - atherosclerosis
2 - peptic ulcers
3 - acute pancreatitis
4 - liver fibrosis
1 - atherosclerosis
- atherogenic and cause plaque formation (stroke and MI)
3 - acute pancreatitis
Prior to statins being developed, what was the main drug of choice to treat hyperlipidaemia?
1 - Fibrates
2 - Cholesterol absorption inhibition
3 - TAG inhibitors
4 - Pancreatic lipase inhibitor
1 - Fibrates
Are fibrates predominately affective at reducing cholesterol or TAGs?
- TAGs
Prior to statins being developed, the main drug of choice to treat hyperlipidaemia was fibrates. Which of the following is the core fibrates drug of choice?
1 - Simvastatin
2 - Atorvastatin
3 - Bezafibrate
4 - Ezetimibe
3 - Bezafibrate
Prior to statins being developed, the main drug of choice to treat hyperlipidaemia was fibrates, with the core drug being Bezafibrate. What is the mechanism of action for Bezafibrate in blood vessels?
1 - inhibit HMG-CoA) reductase
2 - inhibit pancreatic lipase
3 - agonist of peroxisome proliferator-activated receptors (PPARs)
4 - inhibit lipoprotein lipase
3 - agonist of peroxisome proliferator-activated receptors (PPARs)
- major regulator of lipid metabolism
- up-regulation of fatty acid beta-oxidation (produce energy)
- increased lipoprotein lipase mediated lipolysis via PPAR.
What affect do fibrates have on the liver?
1 - decrease beta oxidation
2 - increase beta oxidation
3 - fatty acid synthesis is increased
4 - fatty acid synthesis is reduced
2 - increase beta oxidation
- TAGs are broken down into fatty acids and used as energy, rather than stored as TAGs in VLDL
- increase HDL
Which 2 of the following are indications for the use of fibrates?
1 - adjunct to diet to treat hyperlipidaemia if statin contraindicated
2 - adjunct to appropriate measures for unresponsive hypertension
3 - adjunct to diet and other appropriate measures in severe hypertriglyceridaemia
4 - adjunct for secondary prevention of cardiovascular events
1 - adjunct to diet to treat hyperlipidaemia if statin contraindicated
3 - adjunct to diet and other appropriate measures in severe hypertriglyceridaemia
Why can fibrates increase the risk of gallstones?
1 - less cholesterol so increased pigment stones
2 - increased cholesterol so concentration of bile is thicker
3 - reduces activity of cholesterol 7 alpha-hydroxylase, so less bile
4 - all of the above
3 - reduces activity of cholesterol 7 alpha-hydroxylase, so less bile
