Lipids lectures

Question 1

Ezetemibe

Answer 1

• Blocks NPC1L1
• NPC1L1 is the channel that transports cholesterol from gut to plasma
• Therefore less cholesterol in blood
• Can be used in polygenic hypercholesterolaemia

Question 2

Primary Hypercholesterolemia

Answer 2

• Due to mutations in LDL-R or ApoB

- Rarely, due to mutations in PCSK9 (Evolocumab useful)

Question 3

Mixed Hyperlipidaemia

Answer 3

• ApoE 2/2

- PALMAR STRIAE

Question 4

Polygenic hypercholesterolaemia

Answer 4

• Mutations in NPC1L1

Question 5

Evolocumab

Answer 5

• Blocks PCSK9
• PCSK9 usually degrades LDL-Rs
• Evolocumab prevents degradation of LDL-Rs, so more LDLs are removed from plasma into cells
• Reduces CVAs but no effect on mortality
• Expensive!

Question 6

Hypo-β-lipoproteinaemia

Answer 6

• Mutations in ApoB so there is a truncated protein

- Low LDLs

Question 7

Tangier Disease

Answer 7

• Mutated ABC1

- Low LDLs

Question 8

A-β Lipoproteinaemia

Answer 8

• Deficiency in MTP
• MTP involved in formation of VLDLs
• Low cholesterol

Question 9

Type I Primary Hypertriglyceraemia

Answer 9

• Deficiency of Lipoprotein Lipase/ApoC

- Chylomicrons float to the top

Question 10

Type IV Primary Hypertriglyceraemia

Answer 10

• Deficiency of ApoIV

- No Chylomicrons; VLDLs float to the top

Question 11

Type V Hypertriglyceraemia

Answer 11

• Increases synthesis of TGs

- Chylomicrons float to the top and VLDLs separate

Question 12

Predicting CVS risk

Answer 12

• Best predictor is total cholesterol:HDL

- If there is intermediate/high risk, measure patient’s lipoprotein A (can give nicotinic acid)

Question 13

Management of CVD

Answer 13

• Aggressive management of BP and lipids improves survival
• Lifestyle modification
• Aspirin
• Thiazides
• High dose statins

Question 14

How to treat statin-resistant patients

Answer 14

• Ezetimibe
• Evolocumab
• Fibrates e.g. gemfibrozil - these reduce triglycerides
• Bile acid sequestrants e.g. colestyramine - Lower LDLs, but increase TGs

Question 15

Bariatric surgery

Answer 15

• Morbidly obese >40

- Decrease LDLs and increase HDLs

Question 16

1st line treatment for T2DM

Answer 16

METFORMIN

• Biguanide
• Decreases hepatic glucose production
• Decreases intestinal glucose absorption
• Increases insulin sensitivity

Question 17

2nd line treatment for T2DM

Answer 17

Metformin + 2nd agent

This can be:

• Sulfonylurea
• DPP4 inhibitor (GLIPTINS)
• GLP1 agonists
• Basal insulin

Other drugs:

• Thiazoledinedione
• SGL2 inhibitor

Question 18

Sulfonylurea

Answer 18

Binds to K channels on beta-cells, causing depolarisation and increased insulin release

overall increased sensitivity to glucose

Question 19

DPP4 inhibitors

Answer 19

GLIPTINS!!!

• These bind to DPP4 which usually breaks down GLP1
• Therefore GLP1 lives longer and can signal to the pancreas to make more insulin
• Increases satiety

Question 20

GLP1 agonists

Answer 20

BYETTA (trade name for EXENATIDE)

• GLP1 is a gut hormone
• Signals to pancreas to produce more insulin
• it also increases satiety

Question 21

SGLT2 inhibitor

Answer 21

• EMPAGLIFLOZIN
• Blocks glucose reabsorption in kidneys
• Increases urinary glucose excretion
• Reduces BM and BP
• There is an initial increase in GFR but this resolves

Question 22

How to treat patients with established CVD and poorly controlled blood glucose

Answer 22

• Empagliflozin (SGLT2 inhibitor) or Liraglutide (GLP1 agonist)

As these reduce mortality