3. Lipid Pharmacology

Question 1

What is the primary prevention of hyperlipidaemia?

Answer 1

Statins

• offer 20mg atorvastatin to people who have a 10% or greater 10 year risk of developing CVD
• for people over 85, atorvastatin may benefit in reducing the risk of non-fatal MI
• They decrease synthesis of cholesterol by inhibiting HMG-CoA reductase
• Also increase the uptake of cholesterol into hepatocytes by upregulating LDL receptors

Question 2

What non-pharmacological treatments are there?

Answer 2

Cardioprotective diet
Weight loss
Physical activity
Reduction in alcohol 
Smoking cessation

Question 3

What are the pharmacokinetics of statins?

Answer 3

• Short acting, specific and reversible = simvastatin, lovastatin
• longer lasting = atorvastatin
• oral, at night
• well absorbed
• CYP3A4 metabolism
• glucuronidation
• sim and lova are given in inactive form

Question 4

What adverse effects are there from statins?

Answer 4

May have muscle pain, GI disturbance, insomnia, rash

Rarely get myositis and angioedema

Question 5

What did the 4Ss study find?

Answer 5

Scandinavian Simvastatin Survival Study

• serum LDL reduced by 35%
• Death reduced by 30%
• Death by CHD reduced by 42%

Question 6

What are the overall benefits of statins?

Answer 6

Endothelium function improves
Improved vascularisation of ischaemic tissue
Atherosclerotic plaque stabilisation
Reduces vascular inflammatory response
Reduced platelet activation
Enhanced fibrinolysis
Antithrombotic

Question 7

What are fibrates?

Answer 7

• Agonists at the PPAR-alpha nuclear receptor - regulates lipid metabolism

Therefore:

• increase synthesis of LPL by adipose tissue
• stimulate FA oxidation in the liver
• Increase expression of ApoA1 —> upregulates HDL
• Increases hepatic LDL uptake

Question 8

What are the pharmacokinetics of fibrates?

Answer 8

• Well absorbed
• High degree of albumin binding - have to give increased conc
• Metabolised by CYP3A4
• Kidney excretion

Question 9

What adverse effects may be seen in fibrates?

Answer 9

• Rash, GI disturbance
• Rhabdomyolysis uncommon - renal failure due to lots of proteins being released and glomerular damage
• may cause gallstones

Question 10

What are cholesterol absorption inhibitors?

Answer 10

Increase excretion Of cholesterol/bile acids

• Ezetimibe
• Colestipol, cholestyramine

Question 11

What is the mechanism of ezetimibe (cholesterol absorption inhibitor)?

Answer 11

Inhibits intestinal absorption of cholesterol by interfering with the NPC1L1 transport protein

• means that less cholesterol is taken from intestine into blood
• decreases LDL and VLDL

Question 12

What is the mechanism of colestipol and cholestyramine?

Answer 12

• They bind to bile acid in the gut, trapping it
• this prevents reabsorption, and thus increases excretion
• body diverts hepatic cholesterol to bile acid synthesis
• upregulates LDLR and thus increases LDL removal from blood

Question 13

How does nicotinic acid (niacin) reduce cholesterol?

Answer 13

Liver

• reduces VLDL synthesis
• Reduces VLDL and LDL

Adipose

• reduces hormone sensitive lipase activity
• reduces TG

Reduces catabolic rate for HDL - increases HDL

Increases clearance of VLDL by activating LPL

Question 14

There are also some pharmacokinetics that may need to know on the word document

Answer 14

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