Lipid-lowering drugs Flashcards
Atherosclerosis can cause
CVD as blocks coronary arteries
Intermittent claudication in calf
Hyperlipidaemia Type I
High postprandial chylomicrons
From LPL (or related cofactor) deficiency
Raised TAGs, normal cholesterol
Hyperlipidaemia Type IIa
High LDLs
From lack of LDL receptor or mutations
Raised cholesterol, normal TAGs
Hyperlipidaemia Type IIb
High VLDL and LDL
From familial combined hyperlipidaemia (genetic)
Raised cholesterol and TAGs
Hyperlipidaemia Type III
High IDL
From dysbetalipoproteinaemia, issues with Apo E so IDLs accumulate and some converted to LDL
High cholesterol and TAG
Hyperlipidaemia Type IV
High VLDL
From familial hypertriglyceridaemia (also increased risk of metabolic disease so higher risk of CV event)
Raised TAGs, normal cholesterol
Primary Prevention group (highest risk group factors)
Familial hyperlipidaemias
Diabetes
Chronic Kidney Disease
10 yr CV risk >10%
Secondary Prevention (2nd high risk group)
All with established CV risk and previous events
Treatments for lipid lowering
Lifestyle changes Statins (HMG CoA reductase inhibitor) Ezetimibe Fibrates Lomitapide
Not recommended for CV risk reduction:
Bile acid sequestrants, nicotinic acid, Omega-3
Statins MOA
Atorvastatin, simvastatin, pravastatin etc
HMG CoA reductase inhibitor, the rate limiting step in cholesterol synthesis so less synthesis, more LDL receptors expressed on hepatocytes
Ezetimibe MOA
Inhibits intestinal cholesterol absorption
Fibrates MOA
bezafibrate, fenofibrate, gemfibrozil etc
Acts as ligand for PPAR-alpha and increases FA oxidation in liver + muscle cells, and activates LPL
BA sequestrants MOA
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
Nicotinic acid MOA
Reduces VLDL release, plasma triglyceride and cholesterol, and increases HDL
Omega-3
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
Lomitapide MOA + issues
Prevents chylomicron + VLDL synthesis
Not much known at the moment as limited studies, also very expensive currently so not used often
New possible treatments (+/-)
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
Fibrates uses
First line drugs for people with very high plasma triglyceride at risk of pancreatitis as are more effective at reducing than statins
Fibrates SE
SE: Abdominal effects (nausea, diarrhoea), muscle effects if used in combo with statin
Statins not used when
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
Lomatipide use
Only licensed for patients with homozygous familial hypercholesterolaemia
Statins SE
SE rare but myopathy occasionally in higher risk, higher dose patients
BA sequestrants use
Used as an adjunct in hypercholesterolaemia
BA sequestrants SE
SE: GI disturbance, can cause hypertriglyceridaemia, interferes with fat soluble vitamins
Nicotinic acid use
Used as adjunct to statin if ever, at lowest dose to avoid SE
Nicotinic acid SE
SE: prostaglandin mediated flushing, dizziness, palpitations and GI effects, can be reduced with aspirin
Ezetimibe use
Used mainly as adjunct to statins, or if someone intolerant to statins then helps lower LDLs with little change in HDL cholesterol
Ezetimibe SE
SE: Steathorrea
