Lecture 17: Statins

Question 1

What are the types of plasma lipids?

Answer 1

• Cholesterol
• Triglycerides
• Fatty acids
• Phospholipids

Question 2

What are the cholesterol subfractions?

Answer 2

LDL (adverse effects)
HDL (beneficial effects)
Triglycerides (adverse vascular effects, pancreatitis)

Question 3

What are the effects of lowering cholesterol when its primary and secondary prevention?

Answer 3

Primary prevention
- Reduction in vascular events

Secondary prevention
- Large beneficial effects
- Decrease CVS mortality and mortility
- 1mmol/L reduction -> 25% decrease in vascular events

Question 4

Describe the synergism of TC levels and CHD:

Answer 4

Smoking, DB, hypertension all have synergisitic effects with TC levels to increased incidence of CHD

Question 5

What are the clinical indications for statin use?

Answer 5

Secondary prevention:
- Angina, MI
- CVA
- PVD

Diabetes

Primary prevention
- CVS risk >30% over ten years (could use lower risk but then would have to treat way more people for same effects)

Question 6

Which drugs do you use to lower plasma lipids?

Answer 6

Statins
- Simvastatin (Dec TC, LDL, Trigs, inc. HDL)

Fibrates
- Bezafibrate (Dec trigs, increase HDL)

Ezetimibe (Decrease TC, LDL)

Nicotinic acid (Dec. trigs)

Question 7

What are the indications for statin use?

Answer 7

Primary prevention:
- High CVS risk pts
- Db
- Familial hypercholesteolaemia

Secondary prevention (Imp/.)
- Previous MI, Angina, CVA, TIA, PVD

Question 8

Whats the MoA for statins?

Answer 8

Competitively inhibit HMG CoA reductase
-> Reduces cholesterol synthesis
-> Secondary up-regulation of LDL receptor expression on hepatocytes

Also inhibits isoprenoid production which is why they might be so good in secondary prevention use. plieotropic?

Question 9

What are the SE of statins?

Answer 9

• Myalgias
• Myositis
• Rhabdomyolysis (can be nephrotoxic)
• Deranged LFTs (liver)

Tetarogenic

Question 10

What are the simvastatin drug interactions?

Answer 10

CYP450
- Amiodarone
- Verapamil
- Diliazem
- Erythromycin
- Fibrates

Question 11

How may statins be pleiotropic?

Answer 11

Anti inflam
Anti thrombotic
immune modulation

i.e some benefits before lowering cholesterol but still being proven

Question 12

Whats the indications for fibrate use?

Answer 12

Isolated hypertriglyceridaemia

Combined therapy with statins i.e resistant hypercholesterolaemia problems

Question 13

Whats the MoA of fibrates?

Answer 13

• PPARa agonist (Peroxisome prolferative activated receptor (nuclear)
• Liver and muscle lipid metabolism.
  -> Activates lipoprotein lipase to breakdown TGs
  -> Decrease VLDL production and enhances its clearance
  -> Increase Skeletal muscle FA storage

Question 14

Whats the SE of fibrates?

Answer 14

GI upset
Deranged LFTs
Myositis

Question 15

What is nicotinic acid?

Answer 15

Vit B3

Question 16

What are the side effects of Vit B3?

Answer 16

Gi intolerance
Flushing
Dry skin

use with statin or fibrate

Question 17

How does nicotinic acid work?

Answer 17

• Reduce FA mobilisation from the periphery
• Reduced heaptic triglyceride/VLDL production
• Reduce HDL degredation

Question 18

What are bile acid binding resins?

Answer 18

i.e Cholestyramine
- Bind bile acids
- Stop enterohepatic circulation
- Decreased absorption of exogenous cholesterol
- Increased conversion of endogenous cholesterol to bile acids
- Increased hepatic LDL expression

Question 19

Whats the side effects of bile acid binding resins?

Answer 19

• Not systemically absorbed
• GI side effects DnV
• Impaired vit ADEK absorption
• Intereferes with drug absorption ie digoxin, warfarin, thiazides

Question 20

Write some notes on lipid lowering treatments:

Answer 20

• Lifelong
• Monitor concordance and SE
• Lots of CV benefits evidence
• treatment at a population level esp. important
• Statin treatment is central