Treatment of high-LDL
Therapeutic lifestyle changes
- Smoking cessation
- The TLC diet
- Exercise
-Should be continued even if lipid lowering pharmacotherapy is started
Drug therapy (general)
Should be used only if TLC's fail HMG-CoA reductase inhibitors (the statins) Bile-acid sequestrates Nicotinic acid Vibrates (gemfinrozol)
HMG-CoA reductase inhibitors mechanism of action
-Most effective drugs for lowering LDL
- Reduces LDL, TG
-Increase in HDL
Promotes plaque stability
Reduces risk of cardiovascular events
-Therapeutic uses: Hypercholesterolemia
Post-MI
Primary and secondary prevention of MI
-Effects seen in 2 weeks
Rosuvastatin
Reaches higher levels in asian–> increased risk of hepatotoxicity
HMG-CoA reductase inhibitors adverse effects
Adverse effects
- Headache
- Rash
- GI disturbances
Rare
Hepatotoxicity and rhabdomyalysis
When should you take statins?
In the evening
Have the greatest effect on lipid levels
Nicotinic acid affects
Reduces LDL, TG
Increases HDL
Nicotinic acid
Skin-flushing, itching GI Hepatotoxicity Hyperglycemia Gout arthritis
Prophylaxis of skin flushing w/ nicotinic acid?
Aspirin 30 minutes beforehand
Bile-Acid Sequestrates (Colesevelam)
Newest and better tolerated
Adjusts to statins
Does not decrease uptake of fat-soluble vitamins
Prevents the reabsorption of bile acids
Increases LDL receptors on hepatocytes
Reduction in LDL
Can reduce glucose, useful for diabetics–> monitor hypoglycemia
Colesnvelam adverse effects
Constipation
Fabric Acid Derivatives:
Gemfibrozil (Lopid)
Most effective at lowering TG
Little to no effect on LDL
Can increase risk for rhabdo w/ patients on statins
Displaces warfarin from plasma albumin
Measure INR frequently
Gemfibrozil adverse effects
Myopathy
Hepatotoxicity
Beneficial drug combinations
Niacin/lovastatin
Simvastatin/niacin
Pravastatin/asprin
Atorvastatin/amlodipine