Dyslipidaemia

Question 1

HDL: high density lipoprotein (GOOD)

Answer 1

• Transports cholesterol AWAY from tissues to the liver where its broken down to bile acids/excreted
• Protects against atherosclerosis, CVD
• High levels of HDL = good (>1)

Question 2

LDL: low density lipoprotein (BAD)

Answer 2

• Transports cholesterol from liver to tissues where it can build up in arteries (+ cause plaque formation, vessel narrowing, thrombus/clot formation)
• Low levels of LDL = good (<1)

Question 3

treatment of dyslipademia

Answer 3

statins, ezetimibe, fibrates, ion exchange resins, PCSK9 inhibitors

Question 4

Statins

Answer 4

• Inhibit cholesterol synthesis ?
• Increase hepatic cholesterol uptake from blood
• Reduce total cholesterol, LDL, TG
• Slightly increase HDL

Question 5

Ezetimibe

Answer 5

• Inhibits the intestinal absorption of dietary/biliary cholesterol
• For high cholesterol, other lipid abnormalities – reduces total cholesterol, LDL, TGs + increases HDL
• Used alone, with dietary changes (low cholesterol/fat diet) / statins / fibrates

Question 6

Fibrates

Answer 6

• Reduce TG and LDL levels (increases LDL uptake by liver)

- Increases HDL levels

Question 7

Ion exchange resins

Answer 7

binding negatively charged bile acids and bile salts in the small intestine to interrupt the enterohepatic circulation of bile acids and increase the conversion of cholesterol into bile. Decreased hepatocyte cholesterol content increases LDL receptors.

Question 8

PCSK9 inhibitors

Answer 8

• LDL taken up into the endsome and degraded
binds to the LDLR on the surface of the hepatocyte, leading to the internalization and degradation of the LDLR in the lysosomes, and reducing the number of LDLRs on the cell surface

Question 9

significant side effects and drug-drug interactions of statins

Answer 9

myopathy, myalgia (pain), myositis (inflammation of muscle)

• Rhabdomyolysis (breakdown of muscle) – rare
• Can increase creatinine kinase – monitor – increased levels indicate destruction of muscle/muscle damage
• Peripheral neuropathy – weakness, tingling, difficulty using arms, hands etc
• Side effects: constipation, flatulence, dyspepsia, nausea, GI pain
• Most of the effect will happen with a small dose – increasing the dose will only slightly improve the outcomes, but will have a lot more side effects

Question 10

Drug-drug interactions

Answer 10

• Atorvastatin + simvastatin (CYP3A4) – taking them with antifungals, grapefruit juice etc can increase risk of myopathy
• Fibrates – can increase risk of myopathy
• Stop taking atorvastatin/simvastatin if taking another drug that inhibits CYP3A4
• Don’t use with potent CYP3A4 inhibitors e.g. clarithromycin, erythromycin