Wk-6 Dyslipidaemia

Question 1

What are 3 kinds of lipoprotein and what are their functions?

Answer 1

HDL - high-density lipoproteins - absorbs cholesterol and carries it back to the liver + ↓ risk for heart disease and stroke
LDL - low-density lipoproteins - build up of cholesterol in your arteries/atherosclerosis
Triglycerides - supply energy + combined with cholesterol to ↑ risk of heart diseases

Question 2

What are the roles of weight loss, exercise and diet in the management of dyslipidemia?

Answer 2

• Exercise can help ↓ triglyceride levels and ↑HDL (good cholesterol) levels.
• Combining exercise with weight loss and dietary changes ↓ LDL (bad cholesterol) levels.

Question 3

Describe the mechanism of action of statins

Answer 3

-statins/HMG-CoA reductase inhibitor
Drugs:
- lipophilic statin: passive diffusion/more potent on peripheral tissues, ie Simvastatin, Lovastatin
- Hydrophilic statins: active transport/more potent on the liver, ie Rosuvastatin, Pravastatin

MOA: bind to HMG-CoA to inhibit the cholesterol synthesis through the Mevalonate pathway

CON:

• use with CYP3A4 inhibitors, ie clarithromycin, erythromycin, verapamil
• ↑ CK (creatinine kinase), meaning muscle damage
• Myopathy
• Hepatorenal impairment

AEs:

• myotoxicity, ie myopathy, myalgia
• transient GI symptoms, ie stomach pain, diarrhoea
• peripheral neuropathy
• ↑ aminotransferase (liver damage), meaning liver disease
• sleep disturbance, headache

Question 4

Describe the mechanism of action of ezetimibe

Answer 4

Drug class: dyslipidaemia meds
MOA: block sterol transporter and inhibit intestinal absorption of cholesterol from diet and bile juice

CON:

• may exaggerate gallbladder disease when used with other dyslipidemia drugs
• hepatorenal impairment

AEs:

• ↑ creatinin kinase, and myalgia
• headache, diarrhea
• pancreatitis

Question 5

Describe the mechanism of action of fibrate

Answer 5

Drugs: fenofibrate, gemfibrozil
MOA: ↓ liver production of VLDL, ↑ cellular triglyceride uptake

AEs: ↑ creatinine kinase, myopathy/myalgia

Question 6

Describe the mechanism of action of ion exchange resins

Answer 6

Drugs: Cholestyramine, Colestipol

MOA: inhibits reabsorption of bile acids from the intestine

Question 7

Describe the mechanism of action of PCSK9 inhibitors

Answer 7

Drugs: evolocumab
- Newest on the market
MOA: ↑ LDL receptors on the hepatocytes

Question 8

Identify significant side effects and drug-drug interactions of statins

Answer 8

• Simvastatin cannot be used with CYP3A4 inhibitors, ie clarithromycin, erythromycin, as it may cause metabolic safety issues
• Simvastatin cannot be used at high dose as it may cause muscle wastes (↑ creatine kinase)
• ↑aminotransferase means liver damage
• peripheral neuropathy – weakness, tingling, difficulty using arms, hands etc
• contraindicated in pregnancy – cholesterol is good for foetal growth, can result in abnormalities

Drug-drug interactions:

• stop taking atorvastatin/simvastatin if taking another drug that inhibits CYP3A4
• fibrates – can increase risk of myopathy
• don’t use with potent CYP3A4 inhibitors e.g. clarithromycin, erythromycin

Question 9

Understand that dyslipidemia is only one factor contributing to cardiovascular health and that overall risk of cardiovascular disease should include assessment of all factors

Answer 9

• Don’t act on lipid levels in isolation (unless they’re abnormally high)
• Same with BP – look at the whole picture of the patient – what other factors are present?
• Assess the risk of future CV events (e.g. other risk factors – overweight, smoking, high BP, >older age, ATSI)
• All pts with high absolute risk of CVD: treat with BP lowering and lipid lowering medication + lifestyle interventions