Lipid-lowering drugs

Question 1

Atherosclerosis can cause

Answer 1

CVD as blocks coronary arteries

Intermittent claudication in calf

Question 2

Hyperlipidaemia Type I

Answer 2

High postprandial chylomicrons
From LPL (or related cofactor) deficiency
Raised TAGs, normal cholesterol

Question 3

Hyperlipidaemia Type IIa

Answer 3

High LDLs
From lack of LDL receptor or mutations
Raised cholesterol, normal TAGs

Question 4

Hyperlipidaemia Type IIb

Answer 4

High VLDL and LDL
From familial combined hyperlipidaemia (genetic)
Raised cholesterol and TAGs

Question 5

Hyperlipidaemia Type III

Answer 5

High IDL
From dysbetalipoproteinaemia, issues with Apo E so IDLs accumulate and some converted to LDL
High cholesterol and TAG

Question 6

Hyperlipidaemia Type IV

Answer 6

High VLDL
From familial hypertriglyceridaemia (also increased risk of metabolic disease so higher risk of CV event)
Raised TAGs, normal cholesterol

Question 7

Primary Prevention group (highest risk group factors)

Answer 7

Familial hyperlipidaemias
Diabetes
Chronic Kidney Disease
10 yr CV risk >10%

Question 8

Secondary Prevention (2nd high risk group)

Answer 8

All with established CV risk and previous events

Question 9

Treatments for lipid lowering

Answer 9

Lifestyle changes
Statins (HMG CoA reductase inhibitor)
Ezetimibe
Fibrates
Lomitapide

Not recommended for CV risk reduction:
Bile acid sequestrants, nicotinic acid, Omega-3

Question 10

Statins MOA

Answer 10

Atorvastatin, simvastatin, pravastatin etc
HMG CoA reductase inhibitor, the rate limiting step in cholesterol synthesis so less synthesis, more LDL receptors expressed on hepatocytes

Question 11

Ezetimibe MOA

Answer 11

Inhibits intestinal cholesterol absorption

Question 12

Fibrates MOA

Answer 12

bezafibrate, fenofibrate, gemfibrozil etc

Acts as ligand for PPAR-alpha and increases FA oxidation in liver + muscle cells, and activates LPL

Question 13

BA sequestrants MOA

Answer 13

aka anion exchange resins: colestyramine, colestipol
Bind to + inhibit intestinal BA reabsorption so fats excreted, BA conversion increased so more LDL pulled in from plasma for conversion

Question 14

Nicotinic acid MOA

Answer 14

Reduces VLDL release, plasma triglyceride and cholesterol, and increases HDL

Question 15

Omega-3

Answer 15

Have effect on TAGs and some on cholesterol but no clinical trials showing CVD prevention effectiveness
May be used to treat hypertriglyceridaemia as an adjunct

Question 16

Lomitapide MOA + issues

Answer 16

Prevents chylomicron + VLDL synthesis

Not much known at the moment as limited studies, also very expensive currently so not used often

Question 17

New possible treatments (+/-)

Answer 17

PCSK9 (degrades LDL receptor) inhibitors - monoclonal antibodies proven to be effective
Currently very expensive, multiple injections needed per year so only used in very high risk patients

Question 18

Fibrates uses

Answer 18

First line drugs for people with very high plasma triglyceride at risk of pancreatitis as are more effective at reducing than statins

Question 19

Fibrates SE

Answer 19

SE: Abdominal effects (nausea, diarrhoea), muscle effects if used in combo with statin

Question 20

Statins not used when

Answer 20

Don’t work for homozygous familial hycholesterolaemia as they don’t have LDL receptors
Can’t be given during pregnancy as cholesterol essential for fetal development

Question 21

Lomatipide use

Answer 21

Only licensed for patients with homozygous familial hypercholesterolaemia

Question 22

Statins SE

Answer 22

SE rare but myopathy occasionally in higher risk, higher dose patients

Question 23

BA sequestrants use

Answer 23

Used as an adjunct in hypercholesterolaemia

Question 24

BA sequestrants SE

Answer 24

SE: GI disturbance, can cause hypertriglyceridaemia, interferes with fat soluble vitamins

Question 25

Nicotinic acid use

Answer 25

Used as adjunct to statin if ever, at lowest dose to avoid SE

Question 26

Nicotinic acid SE

Answer 26

SE: prostaglandin mediated flushing, dizziness, palpitations and GI effects, can be reduced with aspirin

Question 27

Ezetimibe use

Answer 27

Used mainly as adjunct to statins, or if someone intolerant to statins then helps lower LDLs with little change in HDL cholesterol

Question 28

Ezetimibe SE

Answer 28

SE: Steathorrea