5. Cholesterol Pharmacology Flashcards
What is the relationship between total cholesterol and CHD mortality?
- high levels of cholesterol in blood serum are associated with a high risk of CHD mortality
- it is however a modifiable risk factor - a 10% reduction in total cholesterol leads to a 15% reduction in CHD mortality
- LDL cholesterol is the primary target to prevent CHD
- there is an association between hypertension, smoking and hypercholesterolaemia
How does LDL cholesterol lead to atherosclerosis?
1) infiltration of LDL cholesterol into the artery wall
2) entrapment of LDL cholesterol
3) modification of LDL cholesterol
4) uptake of modified cholesterol by macrophages
5) formation of foam cells
6) formation of fatty streaks
7) conversion of fatty streaks to fibrous plaques.
As BMI increases your LDL cholesterol can also increase and HDL cholesterol can decrease.
Atherosclerosis is a chronic inflammatory disorder. Explain why Ox-LDL has pro-atherogenic effects?
- reduce macrophage motility
- induce T cell activation
- toxic to endothelial cells
- enhance platelet aggregation
Name the 7 types of lipid lowering drugs
PORN CSF
most commonly prescribed is statins.
P: plant sterols O: omega 3 fatty acids R: resins N: nicotinic acid/niacin C: cholesterol lipase inhibitors F:fibrates
Describe the mechanism of action of statins.
- inhibit cholesterol synthesis in hepatocytes
- blocks the enzyme HMG-coA reductase
- also increase the number of LDL receptors on hepatocytes increasing their uptake and removal from blood
- minor effects include anti inflammatory, plaque reduction and reduced thrombotic risk
What is the difference between primary and secondary prevention of CVD?
Primary: reducing risk mortality in someone who has never had a CVD event but they have other risk factors e.g. diabetes, BP etc.
Secondary: reducing risk mortality in someone who has CVD and has had a CBD event.
Name some adverse effects of statins.
- myopathy: diffuse muscle pain and raised CPK
- hepatocyte toxicity: raised AST levels so LFTs done routinely
- miscellaneous: GI complaints, arthralgia and headaches
Who should be prescribed statins?
- patients who have a 20% risk of developing CVD in the next 10 year
- use a risk calculator
- those who have familial hypercholesterolaemia
Describe the mechanism of action of fibrates.
- increase production of lipoprotein lipase (PPAR agonists)
- increase uptake of chylomicrons and VLDLS
- breaks down triglycerides
- so slightly reduces LDLS and increases HDL cholesterol in patients with hyper triglyceridaemia
Name some side effects of fibrates
- GI symptoms
- gall stones (cholelithiasis)
- inflammation of the muscles (myositis)
- abnormal LFTs
Who do you not give fibrates to?
Those with hepatic or gallbladder disease.
Give as an adjunct to diet modification or with statins.
What is the mechanism of action of nicotinic acid?
- inhibits lipoprotein synthesis
- reduces VLDL synthesis
- increases HDL synthesis more than the other lipid lowering drugs
Name the side effects of nicotinic acid drugs
- flushing: warmth, redness and itching
- hepatocyte toxicity
- headaches
- reduced insulin sensitivity, hyperglycaemia
- GI symptoms - activation of peptic ulcer
Must give aspirin alongside this drug to reduce side effects
Which groups would we not prescribe nicotinic acid to?
- diabetics
- those with peptic ulcers
- anyone with abnormal LFTs or liver disease
Describe the mechanism of action of the cholesterol lipase inhibitor ezetimide
- inhibits cholesterol absorption in the small intestine and decreases delivery of cholesterol to the liver
- increase number of LDL receptors on hepatocytes so they take up more cholesterol, removing it from the blood
