Lipid Lowering Flashcards
What two statins are prodrugs?
lovastatin
simvastatin
Effect of omega-3 fatty acid supplements on blood lipids
decrease TG
Effect of statins on blood lipids
reduce LDL
modest reduction in TG and increase in HDL
higher intensity lipid lowering statin
atorvastatin
metabolized by CYP3A4
atorvastatin
metabolized by sulfating (NOT p450 dependent)
pravastatin
except atorvastatin, statins are administered ______ (time of day), when cholesterol biosynthesis takes place
QHS
half life:
atorvastatin _______ hrs
pravastatin ________ hrs
14 h (take any time) 2 h (take QHS)
statin that is excreted unchanged in urine
pravastatin
statin that is not protein bound
pravastatin
effect of taking food with drug
decreased absorption of drug
statin that crosses BBB
atorvastatin
well known adverse effect of atorvastatin, when combined with gemfibrozil (inhibits uptake) or drugs that inhibit CYP3A4 (TONS!)
myopathy/myalgia
rhabdomyolysis
statin that is hydrophilic and hepatoselective
pravastatin
cholesterol absorption blocker at brush border (inhibits Niemann-Pick C1-Like 1)
ezetimibe (and its glucuronirated metabolite)
increases expression of LDL-receptor (increased clearance)
effect of ezetimibe on lipid levels
decrease LDL, especially as adjunct
combined with statin - no P450 involvement
half life:
ezetimibe
22 hours
long due to enterohepatic circulation
effect of cholestyramine on lipid levels
reduce LDL
modest increase in HDL and TG
binds bile acids in the GI –> excretion
cholestyramine
up regulates LDL-receptor to increase conversion of cholesterol to bile
contraindication to cholestyramine
hyperTG
give this medication 1 hr after or 2 hrs before other drugs
cholestyramine
can bind and impair absorption of other drug
effect of niacin on lipid levels
increases HDL
lowers TG and LDL
inhibits lipolysis in adipose tissue for transport to liver (for VLDL synthesis)
niacin (vitamin B3) at high doses
contraindications for niacin
pregnancy
caution with existing liver and GI issues
adverse effect of niacin
flushing (declines over 1-2 weeks)
hepatotoxicity (heavy first pass metabolism)
Dyspepsia (huge doses!)
effect of fibrates on lipid levels
lower TG
only fibrate shown to impact outcomes:
gemfibrozil
gemfibrozil MOA
agonist for PPAR-alpha receptor (transcription factor)
essentially - decreases TG synthesis and increases clearance
half life gemfibrozil
1.1 hours
adverse effects of gemfibrozil
myopathy
GI discomfort
DRUG interactions due to inhibition of transporter (warfarin, OCP)
contraindications for gemfibrozil
pregnancy
children
best drug for increasing HDL
niacin
best drug for lowering LDL
statins
best drug for lowering TG
fibrates, niacin, omega-3
only gemfibrozil clinically significant
What does PCSK9 do?
binds to LDL-R leading to its degradation
evolocumab (Repatha)
PCSK9 inhibitors
problems with evolocumab
injected only
expensive
nasopharyngitis
?seem not too efficacious?
indication for evolocumab (who gets it?)
familial homozygous hypercholesterolemia
