lipid lowering drugs

Question 1

What are the lipid lowering drugs used?

Answer 1

1. HMG CoA Reductase Inhibitors (targets cholesterol)
   - “Statins”
2. PCSK9 Inhibitors (targets cholesterol for pts intolerant to statins)
3. Fibrates/Fibric acid derivatives (targets triglycerides)
4. Omega-3-acid ethyl esters (targets triglycerides)
5. Niacin (targets triglycerides)
6. Bile acid binding resins (targets cholesterol)
7. Inhibitors of intestinal sterol absorption
   -Ezetimibe

Question 2

Exogenous pathway of cholesterol transport

Answer 2

1. Triglycerides in chylomicrons will be hydrolysed by lipoprotein lipase and the tissues will take up remaining free fatty acid
2. Chylomicron remnants will bind to hepatocyte receptors and undergo endocytosis
3. Cholesterol will be stored, oxidised to bile acids or secreted in bile unaltered

Question 3

Endogenous pathway of cholesterol transport

Answer 3

1. Cholesterol and newly synthesised triglycerides are transported from the liver to adipose tissue and muscle cells via VLDL
2. Triglycerides will be hydrolysed to lipoprotein lipase and lipoprotein particles becomes LDL
3. LDL will be taken up by cells by LDL receptors via endocytosis that recognise LDL apolipoproteins
4. Cholesterol returns to plasma as HDL particles

Question 4

Classification of Hyperlipoproteinaemia

Answer 4

Type 1: Familial Hyperchylomicronemia
Type 2a: Familial Hypercholesterolemia
Type 2b: Familial Combined Hyperlipidaemia

Question 5

What is the problem in Type 1: Familial Hyperchylomicronemia?

Answer 5

Deficiency of lipoprotein lipase

Question 6

What is the problem in Type 2a: Familial Hypercholesterolemia?

Answer 6

Decreased no. of LDL receptors

Question 7

What is the problem in Type 2b: Familial Combined Hyperlipidaemia?

Answer 7

Overproduction of VLDL by liver

Question 8

What is the lipoprotein elevated in Type 1?

Answer 8

Chylomicron

Question 9

What is the lipoprotein elevated in Type 2a?

Answer 9

LDL

Question 10

What is the lipoprotein elevated in Type 2b?

Answer 10

LDL + VLDL

Question 11

Is there atherosclerotic risk in Type 1?

Answer 11

No

Question 12

Is there atherosclerotic risk in Type 2a?

Answer 12

High risk

Question 13

Is there atherosclerotic risk in Type 2b?

Answer 13

High risk

Question 14

MOA of HMG CoA reductase inhibitors

Answer 14

• inhibit HMG CoA reductase inhibitors -> decrease cholesterol synthesis
• upregulate LDL receptors on cell surfaces -> more LDL will be endocytosed and LDL-cholesterol will be internalised

Question 15

Statins are best given at ____. Why?

Answer 15

Night.
Basal HMG CoA reductase activity is highest at night, hence giving statins at night can maximally inhibit the enzyme

Question 16

Adverse effects of statins

Answer 16

Affects liver function
Rhabdomyolysis and myopathy

Question 17

MOA of PCSK9 inhibitors

Answer 17

• blocks PCSK9
• reduces degradation of LDL receptors by lysozymes
• decrease endocytosis of LDL -> less LDL-cholesterol internalised

Question 18

Contraindications using statins

Answer 18

Pregnant, nursing women, children, teenager (affects neurodevelopment of child, foetus)

Question 19

Adverse reactions using PCSK9 inhibitors

Answer 19

Injection site inflammatory response
Nasopharyngitis and Sinusitis

Question 20

Contraindications using PCSK9 inhibitors

Answer 20

Patients with hypersensitivity reactions

Question 21

Omega-3-acid ethyl esters is not indicated for

Answer 21

Type 1 hyperchylomicronemia

Question 22

MOA of bile acid binding resins

Answer 22

• Resins bind to bile acids and bile salts
• Decrease in bile acids conc. will cause increase conversion of cholesterol to bile acids in hepatocytes
• Decrease intracellular cholesterol
• Cause increase uptake of LDL into cells -> decrease plasma LDL levels

Question 23

Adverse reactions of bile acid binding resins

Answer 23

GI effects
Impaired absorptions: vitamin A, D, E, K

Question 24

MOA of Inhibitor intestinal sterol absorption (ezetimibe)

Answer 24

inhibits cholesterol transport protein

Question 25

Does ezetimibe remain effective in the absence of dietary cholesterol?

Answer 25

Yes, it prevents bile salts from re-entering intestine