Lipids lectures Flashcards
Ezetemibe
- Blocks NPC1L1
- NPC1L1 is the channel that transports cholesterol from gut to plasma
- Therefore less cholesterol in blood
- Can be used in polygenic hypercholesterolaemia
Primary Hypercholesterolemia
- Due to mutations in LDL-R or ApoB
- Rarely, due to mutations in PCSK9 (Evolocumab useful)
Mixed Hyperlipidaemia
- ApoE 2/2
- PALMAR STRIAE
Polygenic hypercholesterolaemia
- Mutations in NPC1L1
Evolocumab
- 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!
Hypo-β-lipoproteinaemia
- Mutations in ApoB so there is a truncated protein
- Low LDLs
Tangier Disease
- Mutated ABC1
- Low LDLs
A-β Lipoproteinaemia
- Deficiency in MTP
- MTP involved in formation of VLDLs
- Low cholesterol
Type I Primary Hypertriglyceraemia
- Deficiency of Lipoprotein Lipase/ApoC
- Chylomicrons float to the top
Type IV Primary Hypertriglyceraemia
- Deficiency of ApoIV
- No Chylomicrons; VLDLs float to the top
Type V Hypertriglyceraemia
- Increases synthesis of TGs
- Chylomicrons float to the top and VLDLs separate
Predicting CVS risk
- Best predictor is total cholesterol:HDL
- If there is intermediate/high risk, measure patient’s lipoprotein A (can give nicotinic acid)
Management of CVD
- Aggressive management of BP and lipids improves survival
- Lifestyle modification
- Aspirin
- Thiazides
- High dose statins
How to treat statin-resistant patients
- Ezetimibe
- Evolocumab
- Fibrates e.g. gemfibrozil - these reduce triglycerides
- Bile acid sequestrants e.g. colestyramine - Lower LDLs, but increase TGs
Bariatric surgery
- Morbidly obese >40
- Decrease LDLs and increase HDLs
1st line treatment for T2DM
METFORMIN
- Biguanide
- Decreases hepatic glucose production
- Decreases intestinal glucose absorption
- Increases insulin sensitivity
2nd line treatment for T2DM
Metformin + 2nd agent
This can be:
- Sulfonylurea
- DPP4 inhibitor (GLIPTINS)
- GLP1 agonists
- Basal insulin
Other drugs:
- Thiazoledinedione
- SGL2 inhibitor
Sulfonylurea
Binds to K channels on beta-cells, causing depolarisation and increased insulin release
overall increased sensitivity to glucose
DPP4 inhibitors
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
GLP1 agonists
BYETTA (trade name for EXENATIDE)
- GLP1 is a gut hormone
- Signals to pancreas to produce more insulin
- it also increases satiety
SGLT2 inhibitor
- EMPAGLIFLOZIN
- Blocks glucose reabsorption in kidneys
- Increases urinary glucose excretion
- Reduces BM and BP
- There is an initial increase in GFR but this resolves
How to treat patients with established CVD and poorly controlled blood glucose
- Empagliflozin (SGLT2 inhibitor) or Liraglutide (GLP1 agonist)
As these reduce mortality
