Pharmalogical Control of Hyperlipidaemias Flashcards
Why is pharmacological control of hyperlipidaemia’s important? What is the concern? What is the objective?
Concern = atherosclerosis Objective = prevent SVD
Describe the exogenous pathways for lipid transport
Lipid emulsified by bile acids in GIT
Absorbed –> chylomicrons
TG’s hydrolysed by lipoprotein lipase (muscle/fat)
chylomicron remnants return to liver
Describe the endogenous pathways for lipid transport
1) Liver
- synthesis of cholesterol and TG’s
VLDL secreted
TG removed –> LDL
2) Extrahepatic
- cholesterol from cell turnover –> HDL’s
- cholesterol esters transferred to LDL’s –> liver
- increase in HDL promotes LDL removal
What are LDL’s?
What percentage of circulating cholesterol do they make up?
What are they used for?
low density lipoproteins
60-70%
membranes, steroids, bile acids
LDL’s needed to produce bile, bile needed to absorb LDL’s
What is a normal lipid profile?
What is it called when there are abnormal lipid levels?
What are the main two dyslipidaemias? What can be done to improve them?
Cholesterol less than 5
HDL’s more than 1.2. LDL’s less than 3
dyslipidaemia
increased LDL’s of most cocern –> drugs
decerased HDL’s –> exercise, moderate alcohol
When would drugs to prevent dyslipidaemias be used?
Used even if lipid profile is normal
Only if other risk factors!
Explain the differences between primary and secondary hyperlipidaemia
Primary = genetic
- six phenotypes, differ in lipoprotein class affected
- increased risk of atherosclerosis
Secondary = metabolic disorders
- diabetes, hypothyroidism, renal disease, alcoholism
What are the 6 drugs used to control hyperlipidaemias?
HMG CoA reductase inhibitors Fibrates Bile Acid-Binding Resins Ezetimibe Nicotinic acid Fish oil
HMG CoA reducatase inhibitors
- What is their generic name? Give examples
- What is their mechanism of action?
- What are some consequences of their use?
- What is their clinical use?
- What are the side effects?
- statins e.g. simvastatin
- Potent competitive inhibitors –> decrease cholesterol synthesis
Decrease cholesterol –> inrecease transcription of enzyme and LDL receptor - increased synthesis of cholesterol
increase LDL receptors –> decrease plasma cholesterol, decrease heart disease risk - Effective is lipid is normal but there area other RF’s
- myositis, hepatitis, contraindicated in pregnancy
FIbrates
- Give a named drug example
- What is their mechanism of action?
- When are they used? What are their benefits?
- What are the adverse affects?
- bezafibrate
- Activate nuclear receptors by increase transcription
Increase lipoprotein lipase. Increase uptake of LDL, decrease TG;s in blood. - Used for high TG’s, benefit decrease heart disease risk
- myositis (especially with XS alcohol!)
Bile acid binding resins
- Give a named drug example
- What is there mechanism of action?
- What is an unwanted affect?
- What are the side effects?
- cholestyramine
- bile acids essential for cholesterol absorption, bile acid recycling
Resins not absorbed so lose cholesterol and bile acids
Increases synthesis of bile acids
increase LDL receptors
decerase LDL’s and heart disease - Incerases TG’s! Decreased asorption of fat soluble vitamins
- GI side effects
Strong marketing of yogurts/magerines containing plant sterols/stanols -compete with cholesterol for uptake
Ezetimbe
- What is its mechanism of action?
- What is its two benefits over resins?
- inhibits intenstinal absorption of cholesterol
blocks receptor uptake
but no evidence of decrease atherosclerosis - No effect of absorption of fat soluble vitamins! (unlike resins)
Much higher potency than resins
Nicotinic acid
- What is its mechanism of action?
- What are its uses?
- What are its common side effects?
- decrease synthesis of TG’s –> decreased LDL
- combine with statins +/- resins –> decrease mortality
- intense flush and pruritus (prostaglandins)
Gi upset
high doses –> jaundice
Fish oil
- What are its effects?
- What is its mechanism of action?
- omega-3 TG’s - improves survival after MI
- increase cholesterol (not for use in secondary hyperlipidaemia!)
decreases clotting (alter chemical structure of eicosanoids
Describe the prescribing guidelines:
- primary prevention
- secondary prevention
Drugs for hyperlipidaemias
Primary prevention - statins - can combine with ezetimibe Secondary prevention - statins - fibrate or bile-acid resin if statin not tolerated - nicotinic acid
Hyperlipidaemias
- increased cholesterol –> statin, plus ezetimibe or resin
- increased TG’s –> statin + fibrate (myositis!)
