Block 2-Reymann (Lipid) Flashcards
1
Q
Lipoproteins
A
- Chylomicrons:
- Transport exogenous Trigly from intestine to muscle/Adipose.
- Remnants taken up in liver & secreted in bile
- Oxidized to bile acids or converted to VLDLs
- VLDL: Transport endogenous trigly from liver to Adipose tissue
- They are hydrolized in adipose tissue by lipoprotein lipase to IDL-LDL
- LDL: transport chelosterol from liver to peripheral tissue
- Cleared from plasma via LDL receptors that recogize Apo-B100
- HDL: transports cholesterol from tissues back to liver
- Cholesterol: Excreted from body by Biliary
2
Q
Atherosclerosis & CVD
A
- Risk is associated w/<u><strong>HIGH LDL & LOW HDL</strong></u>
- LDL not taken up by LDL-receptor are oxidized
- Oxidized LDL accumulates in macrophages <u><strong>(FOAM CELL)</strong></u>
- Foam cell undergo apoptotic or Necro death = RELEASE of free radicals
- Oxidzied LDL triggers LOCAL infammatory response = <u><strong>ATHEROSCLEROSIS</strong></u>
- CVD=<u><strong>HIGH LDL </strong></u>(above 130) & <strong><u>LOW HDL</u></strong> (below 35) & <strong><u>HIGH Trigly</u></strong> (above 150)
- Associated w/Alcohol abuse, smoking, hypertension, Type 2 diabetes
3
Q
Dyslipidemia is symptom
A
- Physiological or reactive hyperglyceridema due to excessive<u><strong> alcohol, caloric, or fat INTAKE</strong></u>
- Hypercholesteroemia=excessive fat or cholesterol intake
- Secondary causes:
- Diabetes
- Adipositas (obesity)
- Metabolic syndrome
- Glucocoticoids
- beta-blockers
- Thiazides
- Oral contracep
- 4 classes of dyslipedmias:
- Hypercholesterolemia
- Hypertriglyceridemia
- Mixed hyperlipidemia
- Disorders of HDL metab
4
Q
Hypercholesterolemia
A
- High TPC (total plasma cholesterol)
- HIGH LDL
- Triglycerides are normal
- Polygenic: No defined genetic cause
- Famililal (FH)-Type 2 a Autosomal dom involving defects in LDL receptor
- Heterozygote = TPC 275-500
- Homozygote = TPC 700-1200 <strong>COMPLETE ABSENCE of LDL receptors</strong>
- Familial defective ApoB100= Autosomal dominant mutations decrease affinity of LDL for LDL-R
5
Q
Hypertriglceridemia
A
- HIGH Triglyceride (200-500)
- Familial hypertri: Type 4 common, autosommal dom
- Familial LPL def: caused by absence of LPL, autosomal recessive
- Profound hypertriglyceridemia
- Infants present w/:
- pacreatitis
- Eruptive xanthomas
- Hepato/splenomegaly
- Apoc2 def-RARE
6
Q
Mixed Hyperlipidemia
A
- High cholesterol
- High LDL
- High Triglyceride
- LOW HDL
- Familial combined hyperlipidemia (FCH):TYPE 2b common
- elevated Trigly & cholesterol BUT reduced HDL
- pts present w/features of sedentary lifestyle
- Dysbetalipoproteinemia (Type3):
- Increased chylomicrons & VLDL rem
- Hypertriglyceridemia & Hypercolesterolemia
- Symptoms do NOT present in males until 30 & in females not until menopause
7
Q
Disorder of HDL metab
A
- LOW HDL
- Defects in
- ApoA1 (comp of HDL)
- ABCA1 (helps in formation of HDL)
- LCAT
8
Q
Antihyperlipidemic Drugs
A
- HMG CoA reductase inhibtiors (statins):
- Lovastatin, simvastatin, pravastatin, atorvastatin, Fluvastatin, Rosuvastatin
- Niacin (nicotinc acid, B2)
- Fibrates (fenofibrate & gemfibrozal)
- Bile acid binding agents:
- Cholestyramine, colestipol, colesevelam
- Cholesterol absorption inhibitors:
- Ezetimibe & plant sterols
9
Q
HMG-CoA reductase inhibitors PD&PK
A
- Statins
- 1st line treatment for elevated LDL <u><strong>(HYPERCHOLESTEROLEMIA)</strong></u>
- PK:
- Lovastatin, simvastatin, atorvastatin-P4503A4
- Pravastatin & Rosuvastatin NOT metab by CYP-450s
- PD:
- Inhibit activity of HMG COA reductase
- Depelete intracell cholesterol
- Increase LDL R expression
- Increase LDL uptake
- Homozygotes of familial hyperchol NO LDL receptors do NOT respond to statins
10
Q
HMG-CoA reductase inhibitors SEs
A
- SE (monotherapy):
- Myopathy & or myositis w/<u><strong>RHABDOMYOLYSIS</strong></u>
- Increases transaminase LVLs + liver enzymes
- SE (combo therapy):
- Drug interaction with cytochrome p-450=<u><strong>Metab of other drugs inhibited</strong></u>
- Increased risk of overdose of other drugs
- CI:
- Pregers/Lactation
- Hepatic disease
- Mascular disease
- Use with Bile acid binding agent or Cholesterol inhibitor =<u><strong> ADDITIVE decrease in LDL</strong></u>
- Use with Niacin = <u><strong>Increase risk of Myopathy</strong></u>
- Fibrates (gemifibrozil) =<u><strong> Increase risk of rhabdomyosis</strong></u>
11
Q
Inhibitors of bile acid reabsorption PD&PK
A
- Cholestyramine, Colesevelan, Colestipol
- Second line treatment for LIPID reduction
- PD:
- Cationic resins bind to (-) charged bile acids in SI = Prevention of reabsorb
- Decreased bile acid reabsorb=Increased conversion of **cholesterol to bile acids **
- LDL receptor expression is increased=<u><strong>ENHANCING LDL clearance</strong></u>
- PK:
- Oral water soluble NOT absorbed/metab
- Uncomfortable to ingest-mix with OJ
- Completely excrerted in Feces
12
Q
Inhibitors of bile acid reabsorption Use&SEs
A
- Use:
- Type 2a & Type 2b hyperlipidemia
- Only if isolated increases in LDL
- Mainly used for <u><strong>young pts of hypercholesterlemia</strong></u>
- Safe in Pregers
- Cholestyramine relieves prutitus caused by accumulation of bile acids w/Bililary obstruction
- SE:
- GI related-Constipation, Bloating, Farting
- Decreased absorb of Fat-sol vit (ADEK) & most drugs (digoxin)
- Combo w/ statins OR niacin ADDITIVE reduction of LDL
- CI=upreg VLDL & trigly synthesis CAUTION w/pts <u><strong>hypertriglyceridemia</strong></u>
13
Q
Niacin
A
- Nicotinic acid/Vit B3
- PD:
- Reduces VLDL, LDL & trigly
- In gram doses inhibits lipolysis in adipose
- Decrease in FAs = decrease in Trigly synthesis (Required for VLDL-LDL comes from VLDL)
- Increases HDL
- PK:
- Oral & <u><strong>converted to nicotinamide </strong></u>incorporated into NAD
- Excreted in urine
- Use: when <u><strong>STATINS are CI</strong></u>
- Familial hyperlipidemias (<u><strong>NO LDL-R)</strong></u>
- In combo w/statins for severe Hypercolesterolemias
- SE: Cutaneous flush (vasodialator)
- Impaired insulin sensitivity - NO diabetics
14
Q
Fibrates
A
- Fenofibrate & Gemifibrozil
- _PK: _
- Oral & bound to albumin
- Excreted as <u><strong>glucoronide conj</strong></u>
- PD:
- Reduce VLDLs + TGs W/increase in HDL
- Bind to induce PPAR (peroxisome proliferator-activated receptor)-Expressed on heptocytes, muscle, macrophage, heart
- USE: Treatment of Hypertriglycerolemias
- 1st line for <strong>dysbetalipoproteinemias</strong>
- Se:
- Choleithiasis: GOLD gallstones
- Interactions: competes w/coumadin for plasma binding shites = <strong>+++ anticoag</strong>
15
Q
Cholesterol Absorption Inhibitors
A
- Ezetimibe & Plant Sterols
- PD: Reduce LDL
- Inhibit intestinal absorption of dietary+biliary cholesterol
- reduce LDL inhibiting hepatic production of VLDL
- Reduced hepatic cholesterol-UP regs LDL-Receptor
- _PK: _
- oral & metab in liver/small intest
- USE: complimentary to statins & Treat Primary & familial hypercolesterolemia <u><strong>(statin is CI)</strong></u>
- SE: Diarrhea, rash, angioedema
- CI: Pregers due to lactation
