Fats Flashcards
Give Exogenous (intestine) and Endogenous lipid pathways + Apoproteins involved
Whats a Lipoprotein
Intestines - Give Chylomicrons - w Apo CII (LDL cofactor) + ApoB48
Chylomicrons remove TG by LPL, becoming Chylomicron Remnants (cholesterol rich)
CR then taken up by Liver through ApoE + ApoB48
Liver produces VLDL w ApoB100 + Apo CII
VLDL to IDL to LDL through LPL (Apo CII)
LDL to Liver through LDLR // ApoB100
HDL comes from both intestines and Liver w Apo AII
Apo AII interact a ABC A1 to uptake cholesterol
Lipoprotein involves outer layer of phospholipids plus Apolipoproteins w fats inside;
What are the Lipoproteins involved in Hypercholesterolemia and Hypertriglyceridemia
LDL (CR); VLDL
Atherosclerosis pathophysiology
Note Tunica Intima is
- endothelial
- SELayer - connective tissue
- IEL
Damage to endothelium
LDL goes into tunica intima layer
- Oxidised by ROS
Damage recruits monocytes - differentiate into macrophages - ingest oxidised LDL - forming Foam Cells + Fatty Streaks
Macrophages die and further recruit more cells + inflammation
Damage + Cytokines - signal smooth muscle proliferation and migration from intima to media layer
Smooth muscle cells also ingest lipids to form foam cells
Fibrous caps form over fatty deposits under the intima layer: Intima, Cap, Fats - Atheroma formation
When fibrous cap ruptures, releasing clot-promoting factors - collagen, TF,
Name all classes of lipid drugs
Statins
Ezetimibe
Fibrates
Niacin
Bile Salt Sequestrants
PCSK9 AB
Fish Oil
Statins
Names
MOA
AE
HMG-CoA reductase inhibitor - cholesterol synthesis
- Hepatic cholesterol pool decrease
- Increase LDL receptor
Names: Atorvastatin, Rosuvastatin, Lovastatin
AE: Myopathy, Rhabdomyolysis, Liver, GI
- Oral, Liver
Ezetimibe
MOA
AE
Use
Niemann-Pick C1-Like 1 NPC1L1 receptor inibitor
Cholesterol absorption at Intestines
AE myopathy
Use: w statins as body compensate by increasing absorption in response to statin
Fibrates
Names MOA [4] AE Use ABSOLUTE CONTRA I
Gemfibrozil, Fenofibrate
PPAR- ALPHA agonists - rmb as 2 metab + 2 lipoprotein
(is a nuclear receptor protein)
- Increase FAO,
- Increase LPL synthesis
- Decreases ApoCIII production, allowing increase LDL clearance (ApoCIII inhibit lipolysis)
- Increases Apo AI, AII production - increase HDL production
AE: GI, Myopathy
Use: HyperT
Contra-I: use w statin due to myopathy; Hepatic; Renal too
Niacin
What is niacin
MOA [3+1]
AE [2]
Niacin is B3 after conversion, but only Niacin is active for lipid lowering effect
some GPCR receptors
- also Increase LPL and HDL
- Inhibits HSL, hence less FFA, less TG syn, VLDL, LDL
- also increases HDL, by decreasing catabolism
- antithrombotic effect
AE:
Pruritis, Flushing
GI
Bile Acids Sequestrant
MOA
Use
DDI, AE
Cholestyramine; Positively charged to bind to negative BA
- involved in Micelle formation, Fat emulsification
Binds Bile acids, excrete in stools,
increases LDL R
Use: w statin due to increase in synthesis (HMG-CoA Reductase) in response
DDI: not w other drugs due to binding, Fat absorption decreases
PCSK9 Ab
MOA
Use
Names
Whats Abciximab (IV)
PCSK9 binds to both LDL and LDLR, lysosomal degradation, decreases LDLR recycling
WO PCSK9, LDL-LDLR can be taken in + LDLR recycling
Use: Subcut injection; Use w statin as statin increases LDLR
Evolo-cumab; Alirocumab
Abciximab, a glycoprotein IIb/IIIa receptor antagonist
Fish Oil
MOA
AE
Omega 3 Fatty acids
Decreases TG level
AE: GI
- prolong bleeding time
Principles
Whats first line for hypercholestrol + Mixed
Whats first line for super high TG hence risk acute pancreatitis
What if fibrate therapy then cholesterol still high
Statin,
Fibrate, Niacin, Fish Oil
Statin (notes say can) but both high risk of myopathy
Name 3 statins + Suffix
Contra-I
Pregancy?
Atorvastatin
Rosuvastatin
Lovastatin
Liver
NO
Name 2 PCSK9 AB + Suffix
AE
Pregnancy?
Alirocumab
Evolocumab
Injection sites; Infections
NO
Name 2 fibrates
MOA
Which fibrate w Statin
Gemfibrozil
Fenofibrate
PPAR alpha agonist
Fenofibrate
