Lecture 25 - Lipid Lowering Therapy

Question 1

Cholesterol Subfractions?

Answer 1

Total cholesterol, LDL cholesterol, HDL cholesterol, Triglycerides

Question 2

Why lower cholesterol?

Answer 2

primary prevention: vascular events, small contribution to mortality; secondary prevention: large beneficial effects, decreased CVS mortality and morbidity

Question 3

Clinical assessment?

Answer 3

any organ damage (primary vs. secondary prevention), BP, xanthoma, glucose, fasting fats levels,

Question 4

Who to treat?

Answer 4

secondary prevention (Angina, MI, CVA, PVD), diabetes, familial hypercholesteraemia primary prevention (CVS risk >30% over 10yr)

Question 5

Statins effects?

Answer 5

decrease TC, LDL and Trigs, increase HDL e.g. simvastatin

Question 6

Fibrates?

Answer 6

big decrease of Trigs, increase HDL e.g. Bezafibrate

Question 7

Other drugs?

Answer 7

Ezetimibe (decrease TC and LDL) and nicotinic acid (decrease trigs)

Question 8

Statin mechanism of action?

Answer 8

competitive inhibition of HMG CoA reductase: reduce cholesterol synthesis, secondary upregulation of LDL receptor expression hepatocytes -> decrease in circulating LDL (inflammation also decreases), give at night

Question 9

Statin side effects?

Answer 9

myalgias, myositis, rhabdomyolysis, deranged LFTs

Question 10

Statin interactions?

Answer 10

Cytochrom P450 (verapamil, diltiazem, erythromycin), fibrate

Question 11

Myopathy pathology?

Answer 11

mutation of OATP1B1 channel reduces hepatic drug uptake, causing statin blood conc. to increase and effect muscles

Question 12

Pleiotropic effect?

Answer 12

anti thrombotic, anti inflammatory, immune modulation, benefits before cholesterol drop

Question 13

Fibrates - indications?

Answer 13

isolated hypertriglyceridaemia (after trying diet and exercise), Resistant hypercholesteraemia (combination w statins)

Question 14

Fibrates - mechanism of action?

Answer 14

PPARalpha agonist - lincrease liver and muscle lipid metabolism (VLDL production and clearance, FA muscle stores) and activate lipoprotein lipase (break down TGs)

Question 15

Fibrates - side effects?

Answer 15

GI upset, deranged LFTs, myositis (increased risk w statin)

Question 16

Ezetimibe?

Answer 16

used w statins, reduce cholesterol absorption therefore delivery to liver, increase hepatic LDL receptors, enterohepatic circulation

Question 17

Nicotinic acid?

Answer 17

vit B3, last line combo w statin or fibrate, side effects: GI upset, flushing, dry skin

Question 18

Nicotinic acid MoA?

Answer 18

reduced FA mobilisation and TG/VLDL production, reduced HDL degradation