Ch 35: Anti-Lipidemics Flashcards
Why treat hyperlipoproteinemia?
- Atherosclerosis
- Leading cause of death in western world
- MI, angina, CAD, strokes - Pancreatitis
- from hypertriglyceridemia
RISK FACTORS:
Male
Family history
Hypercholesterolemia (esp LDL)
Lipoproteins
- Lipid core plus proteins (apolipoproteins)
- regulate delivery and off-loading of cholesterol
- B-100-apoprotein on VLDL, LDL, IDL
- tissues can uptake by receptor mediated endocytosis
- it too much, macrophages takes up extra and form foam cells (form atherosclerotic plaques)
HDL
- “GOOD” cholesterol
- takes cholesterol from arterial wall and transports back to liver
- Inhibits oxidation of atherogenic lipoproteins
- low levels are a risk for CAD (coronary artery disease)
Clinical Indicators for CAD
low HDL
high LDL
high total cholesterol
High triglycerides»_space; pancreatitis
Cholesterol Biosynthesis
- Acetyl CoA (from lipid breakdown and glucose oxidation) + Acetyl CoA
- > > > > acetoacetyl CoA»_space;> hydroxy methyl glutaryl CoA
- > > > Mevalonate by way of HMG CoA Reductase
- > > > cholesterol (many steps to cholesterol biosynthesis)
Is cholesterol bad?
- Manufactured by animal cells (most)
- Used in the cell membrane (helps maintain structure and fluidity)
- Precursor molecule for:
sex steroids (E,P,T, etc)
Vitamin D (calcium handling)
bile salts (lipid handling)
Corticosteroids (stress handling)
Treatment for Hyperolipoproteinemia
- Diet
- Drug Therapy
- Statins (Atorvastatin, Simvastatin, Rosuvastatin, etc)
- Mechanism: Block HMG CoA Reductase
* get decreased Cholesterol production
* get increased receptor expression in liver
* increased clearance from plasma
One Statin Study (Scandinavian Simvastatin Survival Study)
- A Scandinavian study over 5 years using simvastatin
- decreased total cholesterol (by 25+%)
- decreased LDL (by 35%)
- increased HDL (by 8+%)
- few side effects/ fairly well tolerated
- BUT, some get liver toxicity
Statins in general
can lower LDL from 25-60%
can increase HDL up to 15%
can lower triglycerides 10-35% or more
- uses at cancer diagnosis linked to lower mortality
Strong statin-diabetes link seen in large study
- Veterans Affairs Research Communications
* Strong statin-diabetes link seen in large study
Statin Issues/Side Effects
- Most common: headaches; GI complaints
- Liver toxicity (only certain patients, may be transient; if 2 tests 2x normal, stop!)
- Can get elevated creatine kinase, along with sore muscles (if greater than 10x normal, discontinue use……. Can get rhabdomyolysis, leading to renal failure)
Resins
- Cholestipol/ Cholestyramine
- Mechanism: cation exchange resin that binds fats and bile acids….. As bile acids excreted, lowers plasma cholesterol as it is taken up to more bile acids
- efficacy: about 15-30% decrease in LDL
- side effects: bloating, GI distress, diarrhea, constipation, nausea, malabsorption
Niacin
- reduce rate of VLDL production and liver secretion (and thus LDL)
- efficacy: about 10-25% reduction and LDL, up to 30% increase in HDL
- side effects: limit usage in 50% of patients…. include headache, flushing, nausea, itchiness, ulcer, liver toxicity
Gemfibrozil/ Fenobibrate
mechanism:
increase lipoprotein lipase
(bind to transcription factor to cause effect)
efficacy:
decrease LDL by about 30% while slightly raising HDL
side effects:
quite well tolerated, but includes dyspepsia, epigastric pain (common), gallstones, others
Ezetimibe
mechanism:
inhibits cholesterol absorption (burst border) and can increase LDL receptors/ removal
decreases LDL (20%) and triglycerides, increase HDL (very slight)
can be used with statins.
WELL TOLERATED
