Hyperlipidemias Flashcards
What is hyperlipidemia?
Increases risk of what diseases?
Defect in lipid transport system that provides cholesterol and trig. to cell
Increase risk of:
- Coronary art disease
- Plauque formation
- Pancreatitis
- Xantoma (fat deposits in skin)
Levels of LDL
100mg/DL=desirable
130mg/DL=2x increase
>160=4x increase
10% decreases in LDL levels→20-30% decrease risk of coronary disease
Secondary Hyperlipoproteinsases
Cirrhosis Alcoholism
Nephrosis Diabetes
Drugs
Primary Hyperlipoproteinsases
Genetic abnormalitites
Decrease LPLiase
Decrease HDL synth
Increase VLDL
Abnormal LDL receptor
Tx of hyperlipidemias
Nonpharmacologic:
- Diet and weight loss (decrease fat and cholesterol)
- Aerobic exercise
- Stop smoking
Pharmacologic:
- Decrease production LPs
- Increase removal of LPs
- Decrease absorption of LPs
“-statin”s
Lovastatin
Bunch of other -statins whose diff is pharmacokinetics
Tx: Hyperlipidemia
Mech:
- Lovastatin is prodrug
-
HMG CoA reductase inhibitor
- Rate limiting step in cell synth of their own cholesterol
- When cells can’t make own cholesterol→increase in LDL receptors→increase LDL uptake
Effects:
-
Best drug for lowering LDL
- Decrease LDL (25%)
- Decrease VLDL synth
SE:
- Myositis (muscle pain)
- At worst→rhabdomyolysis (muscle breakdown)
- Liver toxicity
- Teratogenic–preg. category X
- Some memory loss
Kinetics-metab by P450
Niacin
aka Vit B3
aka Nicotinic acid
Tx: Hyperlipidemia
Mech:
- Inh. enzyme essential for VLDL synth
- May also bind to receptor that decreases VLDL synth
Effects:
- Best at increasing HDL
- Increase HDL
- Decrease VLDL
SE:
- Cutaneous flushing and itching (prevented by aspirin)
- Increase uric acid–>gout
- Increase incidence of diabetes
Gout: -Thiazides, Loop of Henle diuretics, ethanol and Niacin
“Choles- or coles-“
Cholestyramine
Colestipol
Coleselevam
Tx: Hyperlipidemia
Mech: Irreversibly binds bile acids in gut→choles. excreted
Effects:
- Decrease circulating cholesterol
- Increase LDL receptor
Combine w/ statins for additional decrease in LPs
SE:
- No systemic SE-too big to be absorbed
- Can bind drugs
- Digoxin
- Oral anti-coagulants
- Decrease absorption of fat soluble vitamins
- GI upset-nausea
Gemfibrozil
Tx: Hyperlipidemia
Mech: Bind to PPAR-peroxisome proliferation acting receptor
Increase transcription of LPLase
Effects
- Best drug for decreasing triglycerides
- Decrease Trig.
- Decrease VLDL
SE:
- GI upset-nausea, vomiting
- Can displace warfarin from plasma binding sites
Fenofibrate
Tx: Hyperlipidemia
Mech: Bind to PPAR-peroxisome proliferation acting receptor
Increase transcription of LPLase
Effects
- Best drug for decreasing trig.
- Decrease Trig.
- Decrease VLDL
SE:
- GI upset-nausea, vomiting
- Can displace warfarin from plasma binding sites
Omega 3 fatty acids
Tx: Hyperlipidemia
Mech: Inhibit enzyme responsible for Trig synth
Not clear though
Icosapent
Tx: Hyperlipidemia
Mech: Inhibit enzyme responsible for Trig synth
Not clear though
Iomitapide
Tx: Hyperlipidemia
Mech: Inh assembly of VLDL in liver
- Apolipoprotein+cholesterol→(X)→VLDL*
- Enzyme inhibitor*
Enzyme for assembly is also a transporter
SE: hepatotoxicity
Mipomersen
Tx: hyperlipidemia
Antisense oligonucleotide
Mech: Binds to mRNA of ApoB
Prevents Apo from being synth
*(Apolipoprotein)*+cholesterol→VLDL
Must be given by injection
Ezetimibe
Tx: Hyperlipidemia
Mech: Blocks cholesterol transport
SE: Flatulence
