Lipid Regulating Drugs

Question 1

What is the first line of treatment in hyperlipidaemia?

Answer 1

• lifestyle interventions

Question 2

As there are no surgeries available for hyperlipidaemia what are the 2 treatment options available?

Answer 2

• lifestyle interventions
• medications

Question 3

What is 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase?

Answer 3

• enzyme that reduces 3-hydroxy-3-methyl-glutaryl-coenzyme A into mevalonate in cholesterol metabolism

Question 4

Where is 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase active in the body?

Answer 4

• liver

Question 5

Why is 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase so important?

Answer 5

• rate limiting step in cholesterol synthesis
• no HMG-CoA) reductase = no mevalonate and no cholesterol

Question 6

What enzyme is the target for hyperlipidaemia medications?

Answer 6

• 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase

Question 7

What are the first line of drugs for anyone with hyperlipidaemia?

Answer 7

• statins

Question 8

What are the 2 statins that we need to know?

Answer 8

• Atorvastatin (most commonly prescribed)
• Simvastatin (dirty drug)

Question 9

What do statins do to a patients lipid profile?

Answer 9

• ⬇️ cholesterol production by liver
• ⬇️ LDL
• ⬇️ total cholesterol
• ⬇️ triglycerides
• ⬆️ HDL

Question 10

In addition to treating hyperlipidaemia, what else are statins effective for when considering the development of atherosclerosis plaques?

Answer 10

• -anti-inflammation
• cholesterol in plaques

Question 11

Statins are able to reduce all cause mortality, what does this mean?

Answer 11

• reduce death from any cause in patients with arterial disease

Question 12

What are the most common side effect of statins?

Answer 12

• myalgia (most common symptom)
• rhabdomyolysis
• arthralgia (joint pain)
• liver dysfunction

Question 13

What does rhabdomyolysis mean?

Answer 13

• rhabdo = rod like
• myo = muscle
• lysis = breakdown

Question 14

Prior to statins being developed, what was the main drug of choice to treat hyperlipidaemia

Answer 14

• fibrates

Question 15

What is the mechanism of action for fibrates?

Answer 15

Fibrates lower hepatic apoC-III production and increase lipoprotein lipase—mediated lipolysis via PPAR.

Question 16

Fibrates act on peroxisome proliferator-activated receptor (PPAR)-alpha, what is this?

Answer 16

• a ligand-activated transcriptional factor
• upregulation of fatty acid beta-oxidation (produce energy)

Question 17

What is the main fibrate we need to be aware of?

Answer 17

• Bezafibrate

Question 18

What are fibrates, specifically Bezafibrate able to do to the lipid profile?

Answer 18

• ⬇️ LDL
• ⬇️ TAG (main effect)
• ⬆️ HDL

Question 19

What are side effects of fibrates, specifically Bezafibrate?

Answer 19

• GI disturbance (diarrhoea)
• myalgia (muscle pain)
• rhabdomyolysis

Question 20

In addition to statins and fibrates there are bile salt sequestrants. How do these drugs affect cholesterol levels?

Answer 20

• bind to bile acids and stops re-absorption - liver has to use cholesterol to make more bile acids - ⬇️ cholesterol

Question 21

What is the name of the bile salt sequestrants that we need to be aware of?

Answer 21

• Cholestyramine

Question 22

What is the main side effect of Cholestyramine, a bile salt sequestrants?

Answer 22

• GI disturbance (diarrhoea)
• ⬇️ fat soluble vitamines (A.D.E.K)

Question 23

Instead of using Cholestyramine, what is a more commonly used bile salt sequestrants?

Answer 23

• Ezetimibe

Question 24

What is proprotein convertase subtilisin/kexin type 9, more commonly referred to as PCSK9?

Answer 24

• an enzyme involved in cholesterol regulation
• regulates the number of LDL receptors

Question 25

What do PCSK9 inhibitors do?

Answer 25

• ⬆️ number of LDL receptors
• cholesterol