8) Cholesterol

Question 1

Describe the process of atheroma formation:

Answer 1

Endothelial dysfunction
Infiltration and entrapment of LDLs in arterial wall
LDL oxidation causes SMC proliferation and T cell activation
Formation of fibrous cap

Question 2

What are some risk factors for atheroma development:

Answer 2

High BP, smoking, high cholesterol

Question 3

What should normal cholesterol be?

Answer 3

<5mmol/L

Question 4

Name some classes of lipid lowering drugs:

Answer 4

Statins
Cholesterol lipase inhibitors
Fibrates
Nicotinic acid
Resins
Omega 3 fatty acids
Plant sterols

Question 5

What is the mechanism of action of statins?

Answer 5

HMG-CoA reductase inhibitors

Question 6

When are statins prescribed?

Answer 6

Cardiovascular risk prevention and familial hypercholesterolemia

Question 7

What are some side effects of statins?

Answer 7

Increased transaminase levels
Myopathy
GI issues, arthralgias, headaches

Question 8

How can statins be monitored?

Answer 8

LFTs and creatine kinase

Question 9

What are some secondary benefits of statins?

Answer 9

Anti-inflammatory
Plaque reduction
Improved endothelial function
Decreased thrombotic risk

Question 10

Describe the pharmacokinetics of statins:

Answer 10

Extensive hepatic first pass metabolism

Eliminated by liver

Question 11

Name one short acting and one long acting statin:

Answer 11

Simvastatin is short acting

Atorvastatin is long acting

Question 12

What are fibrates and when are they used?

Answer 12

Ampipathic carboxylic acids

Used in hypertriglyceridemia

Question 13

What is the mechanism of action of fibrates?

Answer 13

Peroxisome proliferator-activated receptor agonist - increase production of lipoprotein lipase

Question 14

What are the side effects of fibrates?

Answer 14

GI upset, cholelithiasis, myositis, abnormal LFTs

Question 15

When are fibrates contraindicated?

Answer 15

Hepatic/renal dysfunction

Previous gallbladder disease

Question 16

What effects does nicotinic acid have on lipid profile?

Answer 16

Reduces VLDL and increases HDL

Question 17

What are the side effects of nicotinic acid?

Answer 17

Flushing, itching, headache (give with aspirin)
Hepatotoxicity
Peptic ulcers
Hyperglycemia, decreased insulin sensitivity

Question 18

When is nicotinic acid contraindicated?

Answer 18

Liver disease

Peptic ulcer disease

Question 19

What is the mechanism of action of the cholesterol absorption inhibitor, Ezetimibe?

Answer 19

Blocks cholesterol transport protein NPC1L1 in brush border so less cholesterol to liver

Question 20

How are the systemic side effects of ezetimibe reduced?

Answer 20

Enterohepatic circulation

Question 21

What are the side effects of ezetimibe?

Answer 21

Headache
Abdominal pain
Diarrhoea

Question 22

What combination therapies can be used in lipid lowering?

Answer 22

Statin and fibrate/nicotinic acid/ezetimbe

Question 23

Why does extra care need to be taken when combining fibrates and statins?

Answer 23

Increased risk of myopathy and rhabdomyolysis

Question 24

How do plant sterols reduce cholesterol?

Answer 24

Compete with cholesterol for absorption

Question 25

What are some dietary factors that can reduce cholesterol?

Answer 25

Fish oil, fibre, vit C/E, alcohol (HDL)

Question 26

After CHD assessment, who is offered atorvastatin?

Answer 26

Those with 10% or greater 10 year risk of CHD