B.1 The Statins

Question 1

How do statins work?

Answer 1

Statins are an HMG-CoA reductase inhibitor (inhibits the first step, therefore, inhibits cholesterol synthesis )

The reduction in hepatic cholesterol synthesis leads to an upregulation of hepatic LDL receptors, promoting LDL uptake

Increase the uptake of cholesterol from plasma by the liver (secondary effect)

Question 2

What condition are statins less effective in?

Answer 2

Homozygous familial hypercholesterolaemia, can not make LDL receptor

Question 3

Why are statins highly selective in the liver?

Answer 3

The liver is the main site of cholesterol synthesis and 1st pass metabolism happens meaning about 5% reaches systemic circulations, inhibiting cholesterol synthesis

Question 4

You should consider statins for all high-risk patients irrespective of cholesterol? True or false

Answer 4

True, in a combination of :

beta-blocker.
ACEi
Aspirin
statin

Question 5

What are the nice guidelines 2014 for prescribing patients with statins?

Answer 5

Primary prevention: Use statins in pts with >10% risk of cardiovascular disease

Question 6

Why should most statins be taken at night besides atorvastatin?

Answer 6

Cholesterol synthesis occurs at night except for atorvastatin, which has a high half-life meaning it doesn’t matter when atorvastatin is taken.

Question 7

What are some adverse effects of statins?

Answer 7

Muscle pains

Rhabdomyolysis
(the breakdown of skeletal muscle, the release of myoglobin, blocks renal tubules, severe renal damage disease)

Increase diabetes (but better to treat CV disease) 
Nocebo effect

Question 8

For primary prevention of CV, how much atorvastatin should be given to a patient?

Answer 8

20 mg atorvastatin (low intensity)

Question 9

For secondary prevention (after a heart attack), how much atorvastatin should be given to the patient?

Answer 9

80 mg atorvastatin (High intensity)

Question 10

Do we need to monitor patients with liver disease when taking a statin?

Answer 10

Yes, LFT should be monitored

Question 11

What could be added to a statin to prevent cholesterol absorption?

Answer 11

Cholesterol absorption inhibitor: Ezetimibe
Prevents the uptake of foods containing cholesterol in the GIT.

Monoclonal antibody:Alirocumab
PCSK9 inhibitor
PCSK9 binds to LDL receptors and leads to its degradation.

Alirocumab increases the number of hepatic LDL receptors therefore LDL in the body reduced.

Question 12

How often should alirocumab be administered?

Answer 12

SC administration every two weeks as it has a long half-life, therefore persists in the plasma for longer periods of time

Question 13

How do fibrates work?

Answer 13

Gemofibrozil activates PPAR-alpha, alters lipoprotein metabolism

Also reduces triglycerides- used with when TGs raised

Doesn’t reduce mortality but reduced IHD