exam 2: lecture 3 Flashcards
explain the exogenous pathway breifly.
in the gut, we have FA and cholestrol –> turned into MICELLES via bile salt, which are made in the liver
the micelles goes to the lumen of the enterocytes in the gut
micelels are packaged into triglyerides
cholestrol is taken up by the NEIMANN PICK C1L1, NPC1L1 and FAT takken up too
what are chylomicrons?
FA/triglerrides and cholestrol packaged tg are called chylomicrons
then the chylomircrons goes straight into the lymphatics to give tissue its energy before going to the liver to die
what does lipoprotein lipase do and what happens to the chylomirons remnant?
lipoprotien lipase breaks up the triglyerides and FA.
FA is absorbed by the fat tissues and skeletal muscules for energy
the remnants are PROATHEROGENIC!! (similiar to LDL) theyre taken up by liver via LDL receptors
what are the low intensity statin drugs? which is the FIRST DRUG to come out ? how much LDL do they decrease?
low intensitiy drugs decreases drugs by <30%
(LPSF)
lovastatin 20mg- 1ST DRUG TO COME OUT
pravastatin 10-20mg
simvistatin 10mg
fluvastatin20-40mg
in general, how do statin work?
statin are HMG-CoA reductase inhibitors.
HMG is needed to convert to mevalonate which is needed to make cholestrol synthesis
what are the moderate intensity statins? what % do they decrease LDL?
LDL by 30-50%
LPSF-P
lovastatin 40-80mg
pravastin 40-80mg
simvistatin 20-40mg
fluvastatin 80mg
pitavastatin 1-4mg
what are the high intentsisity statin drugs?
decrease LDL by 50-63%
(AR)
atorvsatain 40-80mg
rosuvastatn 20-40mg
between the statin drugs, which has a a modest inhibition of apoB production by the liver and modest decrease of VLDL?
ATORVASTATIN - uses to lower triglyceride mostly
what is the MOA of statins?
the statins are HMG co-A inhibitors!!
they STOP the production of cholestrol
to make up for this, the liver will INCREASE expression of LDL receptors and will pull LDL from the blood
statin will contribute to modest inhibtion of apoB proudction and modest decrease of VLDL –> usefull if soemone’s triglyeride is well elevated like above 200
what are two 2nd effects to statin drugs? good effects :)
- if you put someone on statin with normal HDL, statin will raise the HDL by 5-10%
BUT, if you put someone on statin with RAISE than normal HDL, nothing will happen - statin drugs inhibits ROS which will decrease inflammmation of atherosclerotic lesions –> which will STOP THE GROWTH OF LESIONS WOW!!!
what is the pharmokinetics of statins? think about if given PO, IV, etc and what two enzymes metabolzies the drugs
given PO at night!!! best time
These two metabolzies the drugs?
CYP2C9 - FPR - fluvastatin, pravastatin, rosuvastain
CYP3A4 - LAS - lorvastatin, atorvastatin, simvastatin
what are the indications for statin meds?
- hypercholeserolemia obviouslly!!!
- DM2 (to lower cholesterol levels
- for acute coronary events ( it can LOWER coronary events
study has shown that a combo drug is really good than alone drug
what are some untoward effects for satin?
- Myalgia!!! (statin can inhbit coQ10 which is needed for ETC which can cause myalgia)
- this is why you put people on satin + coQ10 supplement
- always check CK levels since it can increase in blood with muscuels pain
severe cases: rhabdo
- DRUG TO DRUG! NEVER GIVE STATIN W NIACIN OR FIBRATE BC IT CAN CASUE SEVERE MYOPATHEIS
- NEVER GIVE STATIN W PREG PPL - it can go through the placenta to baby and cause teratogenic!
- ALWAYS CHECK liver enzymes. more than 3 is BAD
explain the MOA of ezetimibe? what year did it come out ?
it came out in 2002
it gets conjugated by the liver with glucoranic acid then it binds to the enterocyte on the lumen. this binding prevents cholestrol from binding and from being taken up via NC1L1 receptor
bc of this, the liver compenstates by taking up LDL from the blood and and increasing LDL receptors = THIS DECREASES LDL = GOOD THING
expplain the pharmokinetics of ezetimbie ?
taking PO
its a prodrug so its absorbed in the gut
gets conjugated with glucoronic acid in the liver so that it easily can bind to the NC1L1 receptor
what are the indication and untoward effect of ezetibmide?
- Hypercholesterolemia!!!
- ezetimbine is better in combo therapy so with a statin or fibrate = decreases extra 10% of LDL
S/E:
HOWEVER, make sure you check hepatic function it can lead to liver diesease, cholesterokl gallstones,
bad for pregnancy people
how do bile acid sequestrant work?
so normally, bile acid is made in the liver and stored in the gallblader. when we eat food, bile acid leaves the gallbadder and helps us reabsorbed the food in the gut, then it gets recylced back into the liver = enterohepatic recycling
normally BAS like cholestyramine is a catonic+ so CL- will bind to it but
when we take a bile acid sequestrant, the drug BINDS TO the bile acid and it prevent entoroheptatic
so this FORCES THE LIVER to make more bile acid so its not going back there anymore so LIVER INCREASES LDL RECEPTOR AND TAKES OUT LDL FROM THE BLOOD
when is enterohepatic recycling ?
so normally, bile acid is made in the liver and stored in the gallblader. when we eat food, bile acid leaves the gallbadder and helps us reabsorbed the food in the gut, then it gets recylced back into the liver = enterohepatic recycling
what are the bile acid sequesrant drugs examples?
B-CCC
* Colestipol
* Cholestyramine
* Colesevelam
which bile acid sqeusret is NOT SYSEMICALLY ABSORBED and what is the benefit?
cholestryamine is not systemically absrobed so its SAFE to give to preg pt or those trying to get preg
what are the indication for bile acid sequesrants?
- hypercholesterolemia! decreases LDL
- PRUITITS + LIVER DISEASE!!!!
- those with liver disease have bile salts getting to the blood and spilling onto the skill casuing nasty prurities. so a bile acid sequerants is perfect to help bring this down!
what are the untoward effect to bile sequesrants?
- GI : bloating and constipation
- VIT K: so bile acids are needed to absorb VIT K for clotting factors
- DRUG TO DRUG –> ezitimide, digoxin, duritiecs, levothyroxin, warfarin, BB
-metabolic acidosis: someone with COPD has a buildup CO2 and someone w diabeties can get ketoacidosis
–> so what happens is that the drug binds to bile salt so CL builds up in the blood and the body will try to compensate and remove another anion so it will remove bicarb and removing bicarb causing metabolic acidosis
what are the two fibrates medication and their half life?
GF
Gemfibrozil - earlier generation, short half life
Fenofibrate - long half life of 18 hours
what is the MOA for fibrates?
fibrates bind to PPAR-a which is a transcription factor for lipid homeostasis. it does the folowing:
casues expression of LPL
LPL is sig becasue it PULL MORE fat/lipids out of blood
it also upregulate apoA1 and 2 which is a component of HDL (remember apoB is a component of LDL)
and it inhibits apoC3 which inhibit lipoprotein lipase
