S3.2 Curbing Cholesterol

Question 1

What are the different classes of lipid lowering drugs?

Answer 1

Statins - simvastatin
Fibrates – fenofibrate
Nicotinic acid/ niacin
Cholesterol lipase inhibitors - ezetimibe

Question 2

What is the mechanism of statins?

Answer 2

Inhibit cholesterol synthesis in hepatocytes by inhibiting HMG-CoA reductase.
Also increases clearance of LDL

Question 3

What are the ADRs of statins?

Answer 3

Increased transaminase levels

Myopathy

Question 4

How do statins reduce CVD risk?

Answer 4

Stabilise atherosclerotic plaques
Improves haemostasis
Reduces inflammation and superoxide formation

Question 5

What is the mechanism of fibrates?

Answer 5

PPARα agonist - increases production of lipoprotein lipase which reduces triglyceride production

Question 6

What are the contraindications of fibrates?

Answer 6

Renal disease

Question 7

What is the mechanism of nicotinic acid?

Answer 7

Reduces VLDL and increases HDL at high doses.

Lipid lowering effect by inhibition of lipoprotein synthesis

Question 8

What are the ADRs of and contraindications of nicotinic acid?

Answer 8

ADRs: itching, headache, activation of peptic ulcer
Contraindications: liver disease

Question 9

What is the mechanism of ezetimibe?

Answer 9

Selectively inhibits intestinal cholesterol absorption by inhibiting NCPC1L1.
Reduces intestinal delivery of cholesterol to the liver

Question 10

What are the ADRs of ezetimibe?

Answer 10

Headache, abdominal pain

Question 11

What is the mechanism of PCSK9 inhibitors?

Answer 11

LDL receptor becomes internalised and inhibited by PCSK9, this draws more cholesterol out of circulation.