Pharmacology Flashcards
(19 cards)
MoA of statins
inhibit HMG coA reductase + other enzymes that catalyze the RL step in cholesterol prduciton inhibitor the liver
—- all statins have mevalonic acid like structure (pharmacophore)
normally acetyl coA converted to melvanoic acid by HMG (stops this process)
Effects of statins on lipid homeostasis
reduce production of cholesterol in liver: increase in LDL R —- increase removal of LDL from blood
reduce VLDL (LDL precursors )
reduce TG + some increase in HDL
How does low cholesterol in liver result in high LDL R expression
high/normal C: sterol regulatory proteins that sit on cell membrane + chill
if cholesterol is low: proteins get unstable + leave cell membrane + each other
—- get broken down + parts of them leave + enter nucleus + bind to sterol regulatory elements (increase gene transcription ) —- increase LDL R
T or F: statins have 2nd mechanisms
T
increase NO production —- vasodilation
increase plaque stability
reduce C reactive protein
antiplatelet effect
Which statins are prodrugs
S + L
SAL —- CYP3A4 metabolized
CYP2C9 —- F
** DI more likely occur if CYP metabolized
MoA of muscle pain /damage + statins
may be a result in changes in membrane composition in muslce + changes in electrical properties with less cholesterol production
—- cholesterol key in membrane fluidity
MoA of fibrates
unclear
—- activation of PPARalpha in liver and adipose
—- increae expression of lipoprotein lipase — decrease TG levels
** increase breakdown of TG rich lipoproteins (chylo + VLDL)
Aes of fibrates
GI, elevation in liver transaminases, gall stones, rash, hair loss, fatigue
MoA: BA resins
anion exchange resigns that contain large highly + polymers (can’t be absorbed by GI)
—- in GI: negative bile acids bind to these. + molecules ++ get excreted in poop
— causes a decrease in BA level (not recycled)— increase liver production of BA —- requires more LDL uptake
Negative: when liver cholesterol decreases —- this activates HMG coA reductase to increase production
——- therefore works best with statins to counteract this
AEs of BA resins
constipation + bloating
DI —- binds to negatively charged things (drugs — thiazide, furosemide, thyroxine) or other cholesterol based drugs
MoA Ezetimibe
blocks luminal cholesterol uptake in jejunum
—- impacts the NPC1L1 transport protein
causes a decrease in cholesterol incorporation into chylos + decrease delivery to liver (liver gets less from outside — increase LDL R levels)
**may increase cholesterol biosynthesis so works better with statins
Niacin is the same as Vit B3
T- water soluble B it’s in ; converted to nicotinamide to fxn as vitamin
— need higher dose then what you get in vitamins
MoA Evolucomab
IgG2 monoclonal Ab that inhibits PCSK9 (enzyme that binds to LDL R to cause them to breakdown )
—- drug stops LDL R destruction — relative increase in LDL R levels
CETP MoA
block transfer of cholesterol from HDL particles to other lipoproteins
—— causes accumulation of HDL —— promotes cholesterol delivery to liver + removal
MoA of ATP citrate lyase inhibitors
stops cholesterol synthesis in liver at earlier stage than statins (before the RLS)
MoA: Angiopoietin like 3 inhibitors
Evinacumab
— binds to Angiopoietin like 3 + prevents it from inhibiting lipase enzymes
MoA: lomitapide
inhibition of microsomal TG transfer protein (normally helps add TG to VLDL + chylos)
—- decrease in VLDL levels
HDL is converted into ______
IDL —- converted into LDL
