Cholesterol Pharmacology

Question 1

If we reduce total cholesterol by 10%, what happens to CHD risk?

Answer 1

15% decrease in CHD mortality

Question 2

What is the primary target in preventing CHD?

Answer 2

LDL cholesterol

Question 3

What does LDL do to vessels?

Answer 3

It infiltrates arterial walls and is trapped in the intima where it undergoes oxidation

Question 4

Why is oxidised LDL bad?

Answer 4

It is pro-atherogenic - inhibits macrophage motility, induces T cell activation, is toxic to endothelial cells, and causes platelet aggregation.

Question 5

What is the most commonly used class of lipid lowering drug?

Answer 5

Statins

Question 6

What effect can statins have on LDL, TAG and HDL?

Answer 6

LDLs fall by 5-35%
TAG falls by 10-35%
HDLs increase by 5%

Question 7

How do statins work?

Answer 7

Inhibit HMG co-a reductase which is integral in cholesterol synthesis

Question 8

What is the result of the action of statins?

Answer 8

Increased LDL and IDL clearance due to increased LDL receptor expression
Decrease VLDL and LDL production

Question 9

What are the indications for statins?

Answer 9

CV risk prevention (Q risk score)

Familial hypercholesterolaemia

Question 10

What is the most common adverse effect of statins?

Answer 10

Myopathy i.e. muscle aches

Question 11

Which enzyme is affected by statins, and in who? (Not HMG co-a reductase, more of an ADR)

Answer 11

Aminotransferase levels are increased in 0.1-2.5% of pts treated. Transient and no long lasting liver damage.

Question 12

When is it most common for myopathy to be experienced with statins?

Answer 12

At higher doses, and if given at the same time as certain other drugs (cyclosporin, gemfibrozil, erythromycin, niacin).

Question 13

Aside from lowering LDL and TAG, what other beneficial affects do statins have?

Answer 13

Anti-inflammatory
Plaque reduction
Improved endothelial function
Reduced thrombotic risk

Question 14

What is the intestinal absorption of statins like?

Answer 14

Variable - 30-85% absorption

Question 15

Why is bioavailability of statins only 5-30% of administered dose?

Answer 15

Variable intestinal absorption as well as extensive 1st pass metabolism

Question 16

When is the peak of cholesterol production in the day/night?

Answer 16

Early in the morning

Question 17

When do pts take short acting statins like simvastatin and why?

Answer 17

Just before bed/at night to coincide with cholesterol produciton peak

Question 18

What is the benefit of long acting statins?

Answer 18

Superior efficacy

Question 19

Aside from statins, what are the other main drugs can we give to lower lipids?

Answer 19

Fibrates/Fibric acid derivatives
Nicotinic acid/niacin
Cholesterol lipase inhibitors

Question 20

How do fibric acid derivatives work?

Answer 20

Peroxisome proliferator-activated receptor agonist

Production of lipoprotein lipase so TAG reduced by a lot

Question 21

What effect do fibric acid derivatives have on LDL?

Answer 21

Modest reduction that depends on which drug is used

Question 22

What are the indications for fibric acid derivatives?

Answer 22

Adjunct with diet modification
Hypertriglyceridaemia
Combined hyperlipidaemia with low HDL

Question 23

What are the ADRs associated with fibric acid derivatives?

Answer 23

GI upset
Gallstones
Myositis
Abnormal LFTs

Question 24

When are fibric acid derivatives contraindicated?

Answer 24

Hepatic or renal dysfunction

Pre-existing gall bladder disease

Question 25

What are the fibirc acid derivatives that can be prescribed?

Answer 25

Clofibrate | Gemfibrozil

Question 26

Which drug is the best at bringing up HDL levels?

Answer 26

Nicotinic acid

Question 27

How does nicotinic acid lower lipids?

Answer 27

Inhibits lipoprotein (a) synthesis

Question 28

What adverse effects can nicotinic acid have?

Answer 28

``` Flushing Itching Headaches Hepatotoxicity Peptic ulcers Hyperglycaemia ```

Question 29

When is nicotinic acid contraindicated?

Answer 29

Active liver disease Abnormal LFTs that are unexplained Peptic ulcer disease

Question 30

How does ezetimide work?

Answer 30

Inhibits intestinal cholesterol absorption and cholesterol lipase enzyme

Question 31

What effects does ezetimide have in the body?

Answer 31

- Decreases cholesterol delivery to the liver - Increases LDL receptor expression in the liver - Decreases cholesterol content in atherogenic particles

Question 32

What are the ADRs associated with ezetimide?

Answer 32

Headaches Nausea Abdo pain Diarrhoea

Question 33

What can we combine for the most effective lowering of lipids?

Answer 33

Statin plus another therapy

Question 34

What therpies can we combine with statins?

Answer 34

``` Fibrate, not gemfibrozil Nicotinic acid Ezetimibe Omega-3 Fatty acids Resins ```

Question 35

How do we decide which therapy to comine with statins?

Answer 35

3 factors - cost, benefit, and ADRs.

Question 36

Why is statin combined with a fibrate potentially contraindicated?

Answer 36

Increased risk for myopathy and rhabdomyolysis

Question 37

What dietary factors can lower lipids?

Answer 37

Fish oils Fibre Vitamin C/E Alcohol (HDL)

Question 38

What dietary elements should we cut down/out to lower lipids?

Answer 38

Fat Dairy Cake/biscuits Alcohol (TAG)