Lipid Metabolism and Drugs Flashcards
equation for total cholesterol
calculated LDL
TC: VLDL(TG/5) + LDL + HDL
calculated LDL = total cholesterol - HDL - TG/5
apoliporprotein B-100
structural protein for VLDL, IDL, LDL, LDL receptor ligand
apolipoprotein C-III
inhibitor of LPL
NPCILI “neimann pick C1 like 1 protein”
transporter of cholesterol into the epithelial cell of small intestine
insulin effects on:
- LPL activity in adipose tissue and muscle tissue
- hormone sensitive lipase
- ApoB100
- increased LPL activity in adipose tissue (LPL chews up chylomicrons into FFA to be stored)
- decreased LPL activity in muscle
- suppression of HSL (dont want to break down adipose tissue, you want to store it)
- ApoB100 production inhbited
metabolic syndrome (related to insulin resistance) leads to these 3 things
- increased TG
- decreased HDL
- small dense LDL
in metabolic syndrome with some degrees of insuline resistance, expalin what happens to the following:
- LPL
- FFA
- Adipose tissue
- Liver TG
- liver ApoB100
- Chylomicron remnant
- HSL
- decreased LPL
- decreased FFA
- decreased adipose tissue
- increased chylomicron remnant (more TG rich, this is what returns to the liver)
- increased Liver TG
- increased HSL (breaking down more of adipose tissue and increasing FFA sent to the liver)
CETP: cholesterol ester transport protein
takes TG from VLDL and LDL and gives it to HDL2 (HDL gives up a CE)
explain what happens to HDL in metabolic syndrome
- build up of TG on VLDL, LDL, and IDL
- takes TG, delivers it to the HDL, and now HDL is TG rich
- HDL more readily metabolized by hepatic lipase, so levels rapidly decrease
- ultimately: low HDL
Ezetimide
- action
- mechanism of action
- side effects
- decreases LDL
- binds directly to NPC1L1 in the gut
- blocks intestinal absorption of cholesterol–>decreased cholesterol delivery to liver –> decreases hepatic cholesterol –> increased LDLR –> decreased serum cholesterol
- increased liver function tests, diarrhea
Phytosterols
- action
- mech of action
- side effect
- natural plant product
- gets excreted from enterocytes, brings cholesterol with it
Cholestyramine, Colestipol, Colesevelam
- action
- mech of action
- side effects
- decreases LDL
- cationic resins bind bile acids –> increase bile acid excretion –> decrease enterohepatic circulation –> liver needs to make more bild acids –> increased LDLR –> decreased serum cholesterol
- increased TG (unclear reasons)
- bloating, bad taste, colesterol gallstones (URQ pain), can’t absorb fat soluble vitamins
Statins
- action
- mech of action
- side effects
-
greatly decreases LDL
- competitive inhibitor of HMG-CoA reductase (rate limiting step in cholesterol synthesis) –> decreased hepativ cholesterol –> increase LDLR –> decreased serum cholesterol
-
decreases TG
- increasaed LDLR (apopB100 and E) –> increased removal of IDL –> decreased production of VLDL due to reduced synthesis of cholesterol, a require component of VLDL
- increased liver function tests, rhabdomyolysis
Gemfibrozil, Fenofibrate
- action
- mech of action
- side effects
Fibrates
- TG breakdown, decreases TG
- decreases C-III (part of VLDL that inhibits LPL) –> upregulates LPL –> decreased TG
- direct stimulation of LPL synthesis
- activates PPAR-a (receptor that modulates carb and fat metabolism)
-
increases HDL
- decreases TG rich VLDL, IDL, LDL –> decreases transfer of TG by CETP to HDL –> decreased HDL metabolism since not as TG-rich –> increased serum HDL
- increases structural components of HDL (apoA1 and apoA11)
-
decreases LDL
- increases LDL receptors
- myositis, increased LFTs, cholesterol gallstones
-
Niacin
- action
- mech of action
- side effects
Vitamin B3- used for patients with low HDL levels
- decreases TG
- inhibits HSL with decreased FFA –> liver
- decreased FA –> decreased TG –> decreased VLDL production
- increases LPL activity
- decreased LDL
- decreased VLDL production
- increased HDL
- decreased TG rich VLDL, IDL, and LDL, decrease TG transfer to HDL
- flushing, hyperglycermia, hyperuricemia
- blunt red face with aspirin
omega 3 FAs
- action
- mech of action
- decrease TG
- cause significant rise of LDL-used for only one reason: to decrease TG
- not first line of therapy
- inhibit hepatic TG synthesis
- increased beta oxidation
- increase degradation of apoB100 (so less VLDL)
- increase LPL activity
Therapy for Homozygous Familial Hypercholesterolemia + complications
- Apo B 100 inhibitors (substrate for LDL)
- decreases LDL
- less VLDL is being released from liver since it also needs apoB100
- complication: fatty liver since not removing VLDL
- microsomal triglyceride transfer protein inhibitors (MTTP puts stuff together to make VLDL)
- decrease hepatic formation of VLDL
- decreases formation of chylomicrons in the intestine
Two new potential drug therapy and mechanisms
- CETP inhibitors
- decrease transfer of CE from HDL to VLDL, LDL, and IDL
- increases HDL, decreases LDL
- PCSK9 inhibitors
- normally made in liver, binds and degrades LDL receptor
- inhibitors increase LDL receptors –> decrease in LDL cholesterol
what is the core of chylomicrons and VLDL
TG
2 main roles of Lipoprotein lipase (LPL)
- hydrolyzes triglycerides
- facilitates cholesterol transfer to HDL
xanthomas
- plaques of lipid-laden histiocytes
- on eyelids or skin
- sign of hyperlipidemia
Type I hyperchylomicronemia
- cause
- inheritance
- effect
- complications
- LPL dysfunction (or deficient in C-II)
- increased TG and chylomicrons
- autosomal recessive
- pancreatitis, enlarged liver, xanthomas
Type II Hypercholesterolemia
- cause
- inheritance
- effect
- complications
- few or no LDL receptors
- very high LDL
- autosomal dominant
- tendon xanthomas, corneal arcus
list the drugs associated with the side effect:
-increased liver function tests
- statins
- ezetimide
- fibrates
list the drugs associated with the side effect:
cholesterol gallsones
- fibrates
- bile resins
list the drugs associated with the side effect:
rhabdo/myositis
- statins
- fibrates
list the drugs associated with the side effect:
bloating/diarrhea
- ezetimide
- bile resins
think ones involved with STOMACH and digestion
