Anti Lipid Drugs Flashcards
moa of HMG CoA reductase inhibs
block synthesis of CE and increase LDL uptake via receptors
extra CV benefit of statins
reduce plt activation and VTE risk
when to take statins
at night, peak CE synth b/w midnight and 2
pregnancy and statins
bad! category X, CE necessary for embryo formation, switch to BABAs for lipid control
statin toxicities
hepatotoxicity- esp w/ underlying liver disease
myopathy-low baseline risk but higher w/ age, dose, hepatic/renal dysfn, other drugs; can progress to rhabdomyolysis
some risk of insulin insensitivity
3 key drugs that interfere with statin metabolism and the enzyme involved
gemfibrozil, amlodipine, warfarin- inhibit CYP3A4 which inactivates simvastatin, lovastatin, atorvastatin
amlodipine and statins
lower dose, inhibition of CYP3A4 raises risk of myopathy
major effect of statins
significant lowering of LDL and TG, nothing for HDL
BABA moa
increase elimination of bile acids, pushing CE towards more bile acid formation
BABA ex
colestipol
PK of BABA
needs to be given in GRAMS, used as alt to statins in pregnancy, can be used w/ statins
BABA toxicities
no systemic toxicities, but GI may be severe
drug interaction w/ BAB
BABA reduce absorption of drugs from GIT, take other drugs hours before or after BABA
effect of BABAs
lower LDL, slight raise in HDL
what is niacin how much is given
vitamin B3, doses of 1-2 grams
niacin moa
inhibit synthesis of TG in liver
toxicities of niacin
flushing and pruritus
hepatotoxicity and insulin resistance (caution w/ diabetics)
niacin effects
lowers LDL, SIGNIFICANT TG lowering, significant HDL raising
fibric acid derivatives moa
increase LDL receptor expression, activate LPL, increase FFA metabolism
toxicities of fibric acids
myopathy when used in common w/ high dose statins (FAD inhibit statin absorption in liver)
important drug interaction for FADs
oral anti coag like warfarin, competes at albumin binding site and increases serum free warfarin and bleeding risk
2 FAD exs
gemfibrozil, fenofibrate
effects of FAD
variable LDL lowering, significant TG lowering, minor HDL increase
ezetimibe moa
blocks CE absorption from intestines at NPC1 receptor, indirectly stimulating LDL-R expression
homeostatic response to ezetimibe/statins
to ezetimibe- increase CE synthesis, to statins- increase absorption
vytorin moa
combine ezetimibe and statins- block absorption and synthesis
ezetimibe effects
lower LDL only
vytorin effects
even more significant lowering of LDL than statins alone
PSK9 inhibitor mechanism
promote CE uptake in liver by inhibiting PSK9 protein that induces LDL-R degredation therefore raising number of LDL-R
PSK9 inhib ex and structure
alirocumab, mab and must be injected biweekly, very expensive
PSK9 inhib effect
very significant LDL reduction, more than statins
