Hyperlipidaemia

Question 1

Describe the relationship between atherosclerotic plaques and cholesterol. (7)

Answer 1

In the form LDL, cholesterol is likely to accumulate in the intima of arteries, be oxidised, and be taken up into macrophages to form foam cells. These foam cells form a fatty streak, which causes chronic inflammation and disrupts the smooth muscle of arteries. This then forms atherosclerotic plaques in time.

Question 2

Describe “good cholesterol”. (2)

Answer 2

In the form HDL, excess cholesterol is returned to the liver for metabolism.

Question 3

Describe the relationship between CVD and cholesterol. (5)

Answer 3

Having high serum cholesterol increases the risk of CVD. It is important because it is a modifiable risk factor for CVD (lowered with diet and exercise changes), unlike age, genetics, being male.

Question 4

Describe statins.
MoA (3)
Benefits of statin therapy (5)

Answer 4

Competitive inhibition of HMG-CoA reductase which upregulates hepatic LDL receptors to reduce circulating LDL.

Improves vascular endothelial function (vasodilation)
Stabilises atherosclerotic plaques
Improved haemostasis
Anti inflammatory
Antioxidant (reduces superoxide formation)

Question 5

Name two statins.
Give the common feature to all statin names.
(3)

Answer 5

-statin
Atorvastatin
Simvastatin

Question 6

Describe the pharmacokinetics of two statins. (4)

Answer 6

Atorvastatin - active derivatives - t1/2 is 30h

Simvastatin - prodrug - t1/2 is 2h

Question 7

Describe the ADRs of statins. (6)

Answer 7

Accumulation of drug can cause liver damage
Myalgia - esp if in high dose or with other cholesterol lowering agents, amioderone or ciclosporin (anti-T cell)
Rhabdomyolysis (rare)
GI disruption inc nausea
Headaches.

Question 8

Define NNT (2)
Describe the NNT for statins and explain what this means.  (3)

Answer 8

“Number needed to treat” - the number of people that need to be treated with a certain thing to prevent one bad outcome.
For statins it is 20 - for every 20 people on statins, one negative outcome is prevented. This means that statins are really successful at preventing the bad outcome, in this case often an MI.

Question 9

Describe the NICE guidelines for Statin therapy. (10)

Answer 9

Reduces all cause mortality following MI
Primary prevention - 20mg Atorvastatin if with a 10 year CVD risk of over 10%
Secondary prevention - 80mg Atorvastatin.
If in CKD -20mg
Avoid grapefruit
Take dose at night to catch the higher LDL receptor synthesis at night.

Question 10

Describe fibric acid derivatives as a drug class. 
MoA (3)
Common indication (1)
Side effects. (3)
Contraindications. (3)

Answer 10

Activation of nuclear transcription factor, which increases production of lipoprotein lipase, and removes triglycerides and fatty acids from the plasma.
Most commonly prescribed in familial hyperlipidaemia.
Side effects include GI upset, gallstones, abnormal LFTs.
Contraindications include hepatic or renal dysfunction, gallbladder disease, warfarin.

Question 11

Name two fibric acid derivatives. (2)

Give the common factor in the names of all fibric acid derivatives. (1)

Answer 11

-fibrate

Fenofibrate, Ciprofibrate.

Question 12

Describe nicotinic acid.
MoA (3)
Common indication (1)
ADRs (6)

Answer 12

Nicotinic acid is a form of vitamin B3 that decreases triglyceride synthesis to lower VLDL and LDL, but increase HDL.
Given most commonly in familial hyperlipidaemia.
Common ADRs include flushing headaches and itching due to prostaglandin release (treat with low dose aspirin), as well as hepatoxocity, and GI disturbances. Often poorly tolerated.

Question 13

Name the one vitamin B3 derivative used in the treatment of hyperlipidaemias. (1)

Answer 13

Niacin

Question 14

Describe cholesterol absorption inhibitors.
MoA (3)
Common indication (1)
Side effects (2)

Answer 14

Act on the brush border of the SI to reduce cholesterol absorption. Also increases expression of hepatic LDL receptor expression.
Commonly taken with a statin that can only be tolerated at low doses.
Generally well tolerated, but can cause headache, abdominal pain, diarrhoea.

Question 15

Name one cholesterol absorption inhibitor. (1)

Answer 15

Ezetimibe

Question 16

Describe the use of monoclonal antibody therapy in hyperlipidaemia. (2)
MoA (3)

Answer 16

Use is limited - needs expensive lifelong injections, but it very effective.
Inhibits the PCSK9 receptor (normally degrades LDL receptors) to increase the number of LDL receptors, so plasma LDL falls.

Question 17

Describe non-prescription medication options for lowering the lipid profile of the blood. (5)

Answer 17

Plant sterols - found in grains and legumes - similar in structure to cholesterol, so compete for absorption and lower cholesterol absorption.
Other good things - fibre, fish oils, vitamins C + E.

Question 18

Explain why lifestyle changes will have a small effect when taking ezetimibe than when taking atorvastatin. (4)

Answer 18

Ezetimibe inhibits cholesterol absorption, so there is less cholesterol in the blood anyway (so eating plant sterols to reduce cholesterol absoroption will have little effect).
But with steroids, the removal of cholesterol from the blood is increased, so being bile to reduce the amount of cholesterol in the blood initially would be helpful.

Question 19

Describe the cost considerations when implementing treatment for hyperlipidaemia. (3)

Answer 19

Diet and exercise changes are cheapest
Statins are also very cheap
Other drugs are more expensive.

Question 20

Describe two methods for assessing CVD risk (3)

Answer 20

Manchester tables - a score based on age, HDL, systolic BP, and smoking history.
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