Lipidaemias And Lipid Lowering Drugs 2 Flashcards
What are the dietary control requirements ?
Consume < 200 mg/day of ch
Total fat per day < 30% - better to have mono or polyunsaturated fat
What are the treatment strategies for hyperlipidaemia ?
Controlling dietary intake of cholesterol and other fats
Pharmacological intervention
When is drug treatment essential in patients with hyperlipidaemia ?
Patients suffer from CAD or its thought they might
It’s primary so it’s caused by a defect in LDLRs
What are the main types of drugs for the treatment of hyperlipidaemia ?
HMG CoA reductase
Fibrates
Bile acid binding resins
What is the aim of HMG CoA reductase and examples ..
Statins- atorvastatin, simvastatin and pravastatin
Inhibit endogenous ch synthesis in the liver
Mainly used if patients have high LDL or VLDL
What is the mechanism of action of statins ?
HMG CoA reductase is the rate limiting step in the production of ch
It converts HMG CoA to mevalonate - by preventing. This it prevents mevalonate being turned into ch
- act as false substrate by being hydrolysed in liver into active form which has a similar structure to intermediate of mevalonate so it binds prevent HMG CA isn’t converted
What does low LDL levels cause ?
Synthesis of LDL receptors - increasing clearance of LDLs in the blood - reduces levels by 20-40%
What are the unwanted effects of statins ?
Can increase liver enzymes
Cause abdominal pains and nausea
Can cause muscle pains or weakness
Can curse renal failure
What are the additional beneficial effects of statins ?
Improve elasticity of endothelium Reduce platelet aggregability Increase neo vascularisation of ischaemia tissue Antithrombic action Atherosclerotic plaque stabilisation Immune suppression
When can statins not be used ?
In pregnancy
In breast feeding
History of liver disease - can up regulate oh her enzy,es
Can’t used used with high alcohol intake
When are fibrates used and examples ?
Gemfibrozil and fenofibrate
Used against high VLDL levels
Agonists at PPAR-alpha: beta oxidative degradation of fatty acids
What is the mode of action of fibrates ?
Increase activity of lipoprotein lipase
Increases catabolism of VLDLs and IDLs
- this increases HDLS-ch
- normally the ch would be transferred to VLDLs but because they are reduced it can’t be exchanged so it reduces LDLs too
What are the unwanted effects of fibrates ?
Generally well tolerated
Can cause muscular damage - this can lead to kidney and renal failure
When are bile acid resins used and examples …
Cholestyramine and colestipol
Used against high LDLs
Unlikely to be taken on own
What’s the mechanism of action of bile acid binding resins ?
Bind to bile acids
This reduces the amount of bile acid so it prevents the negative feedback of bile acids onto the enzyme which converts ch to bile acids therefore more ch will be converted to bile acids
However bile acids needed to absorb cholesterol and the liver requires some ch so it causes liver to increased HMG CoA reductase activity and increase LDL receptors
Overall loss of ch
