Lipid lowering drugs

Question 1

List the 4 main classes of lipid lowering drugs

Answer 1

• statins
• cholesterol lipase inhibitors
• nicotinic acid/ niacin
• fibrates

Question 2

give 2 examples of statins

Answer 2

atorvastatin, simvastatin, pravastatin

Question 3

How do statins work?

Answer 3

Inhibit HMG co- a reductase, which decreases lipid synthesis in the liver, so increases LDL receptors and decreases production of LDLs

Question 4

Who should receive a statin?

Answer 4

Anyone with a >10% risk of developing CVD in the next 10 yrs and those with familial hypercholesterolaemia

Question 5

State 3 common side effects of statins

Answer 5

• Muscle and joint aches and pains–> creatine kinase may be raised, often seen with higher doses
• GI upset
• headaches

Question 6

What effect can statins have on the liver which warrants LFT monitoring as they start treatment?

Answer 6

In rare cases it can increase transaminase levels, no chronic liver disease persists and is rapidly reversible on stopping treatment

Question 7

What secondary benefits can statin have?

Answer 7

anti- inflammatory, plaque reduction, improved endothelial function, reduced thrombus risk

Question 8

Name 2 fibric acid derivatives?

Answer 8

bezafibrate, fenofibrate

Question 9

How do fibric acid derivates work to reduce cholesterol?

Answer 9

They are peroxisome proliferation activated receptor agonists, so increase lipoprotein lipase and so reduce TAG production. Also some knock on LDL decrease.

Question 10

When are fibric acid derivates used?

Answer 10

adjuncts to statins/ diet therapy and in familial hypertriglyceridaemia

Question 11

Name 3 ADRs of fibric acid derivates

Answer 11

• GI upset
• Gall stone risk
• muscle inflammation

Question 12

When are fibric acid derivates contraindicated?

Answer 12

• hepatic and renal dysfunction

- pre- existing gall bladder disease

Question 13

Name one nicotinic acid drug used to lower cholesterol?

Answer 13

Niacin

Question 14

When is niacin indicated and contraindicated?

Answer 14

Indication: alongside statins
Contraindication: Liver disease of unexplained LFT elevation, also peptic ulcer disease

Question 15

Name 3 ADRs seen with nicotinic acids?

Answer 15

• Flushings, itchings, headahces
• hepatotoxicity
• GI Upset
• Peptic ulcers
• reduced insulin sensitivity

Question 16

How do nicotinic acids work?

Answer 16

Inhibit lipoprotein synthesis, so reduced VLDL and LDL, also good at increasing HDL

Question 17

Name one cholesterol lipase inhibitor

Answer 17

Ezetimibe

Question 18

How does ezetimibe work?

Answer 18

inhibits cholesterol lipase so inhibits cholesterol absorbtion on brush boarder of intestine, so less LDL delivery to liver and upregulation of LDL receptors. It never enters the systemic circulation.

Question 19

When is ezetimibe used?

Answer 19

as adjunct to statins or when theyre poorly tolerated

Question 20

What ADRs may arise from cholesterol lipase inhibitors?

Answer 20

Headache, abdo pain, diarrhoea

Question 21

Why are resins not often used now to lower cholesterol?

Answer 21

theyre poorly tolerated

Question 22

What new therapies could be used in the future to lower cholesterol?

Answer 22

PCSK9 inhibitors (evolocumab)- monoclonal antibodies to a protein which destroys the LDL receptors. Very effective but far too expensive for widespread use.

Question 23

What dietary factors can reduce cholesterol?

Answer 23

fish oils, fibre, vitamin C and E, alcohol and plant sterols

Question 24

How is CVD risk calculated?

Answer 24

Using Qrisk2 calculator.

Takes into account age, sex, postcode, race, BMI, smoking, Fhx, AF, CKD, BP, Cholesterol and HDL levels

Question 25

What % reduction in non HDL cholesterol is aimed for?

Answer 25

40%

Question 26

What dose of atrovastatin is generally used?

Answer 26

20mg for primary prevention with elevated CVD risk.

80mg for primary prevention if already have CVD- if can tolerate this high a dose.