Lecture 17: Statins Flashcards
What are the types of plasma lipids?
- Cholesterol
- Triglycerides
- Fatty acids
- Phospholipids
What are the cholesterol subfractions?
LDL (adverse effects)
HDL (beneficial effects)
Triglycerides (adverse vascular effects, pancreatitis)
What are the effects of lowering cholesterol when its primary and secondary prevention?
Primary prevention
- Reduction in vascular events
Secondary prevention
- Large beneficial effects
- Decrease CVS mortality and mortility
- 1mmol/L reduction -> 25% decrease in vascular events
Describe the synergism of TC levels and CHD:
Smoking, DB, hypertension all have synergisitic effects with TC levels to increased incidence of CHD
What are the clinical indications for statin use?
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)
Which drugs do you use to lower plasma lipids?
Statins
- Simvastatin (Dec TC, LDL, Trigs, inc. HDL)
Fibrates
- Bezafibrate (Dec trigs, increase HDL)
Ezetimibe (Decrease TC, LDL)
Nicotinic acid (Dec. trigs)
What are the indications for statin use?
Primary prevention:
- High CVS risk pts
- Db
- Familial hypercholesteolaemia
Secondary prevention (Imp/.)
- Previous MI, Angina, CVA, TIA, PVD
Whats the MoA for statins?
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?
What are the SE of statins?
- Myalgias
- Myositis
- Rhabdomyolysis (can be nephrotoxic)
- Deranged LFTs (liver)
Tetarogenic
What are the simvastatin drug interactions?
CYP450
- Amiodarone
- Verapamil
- Diliazem
- Erythromycin
- Fibrates
How may statins be pleiotropic?
Anti inflam
Anti thrombotic
immune modulation
i.e some benefits before lowering cholesterol but still being proven
Whats the indications for fibrate use?
Isolated hypertriglyceridaemia
Combined therapy with statins i.e resistant hypercholesterolaemia problems
Whats the MoA of fibrates?
- 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
Whats the SE of fibrates?
GI upset
Deranged LFTs
Myositis
What is nicotinic acid?
Vit B3
What are the side effects of Vit B3?
Gi intolerance
Flushing
Dry skin
use with statin or fibrate
How does nicotinic acid work?
- Reduce FA mobilisation from the periphery
- Reduced heaptic triglyceride/VLDL production
- Reduce HDL degredation
What are bile acid binding resins?
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
Whats the side effects of bile acid binding resins?
- Not systemically absorbed
- GI side effects DnV
- Impaired vit ADEK absorption
- Intereferes with drug absorption ie digoxin, warfarin, thiazides
Write some notes on lipid lowering treatments:
- Lifelong
- Monitor concordance and SE
- Lots of CV benefits evidence
- treatment at a population level esp. important
- Statin treatment is central
