lipids Flashcards
drugs that decrease cholesterol
HMG-CoA reductase inhibitors (statins)
cholesterol absorption inhibitors
bile acid sequestrants
nicotinic acid
drugs that decrease triglycerides
fibric acid derivatives
omega-3 fatty acids
nicotinic acid
main MOA statins
- inhibits 3-hydroxy-3-methylglutaryl (HMG) coenzyme A conversion to mevalonate, the rate limiting step preventing intracellular cholesterol biosynthesis
- causes up-regulation of LDL-Rs and inc removal of LDL chol from plasma (main effect)
other effects of statins
inhibits vascular SM proliferation, inhibits platelet-thrombus formation, anti-tumor effect, endothelial protection
*secondary prevention of MI, CAD, etc (they’ve had one before) but no primary prevention
absorption of statins with food
must give lovastatin with food
others have no or slight decrease in absorption with food
half lives and time of administration of statins
most have short half-lives, give at night (HMG-CoA activity highest from midnight-3 am)
EXCEPT atorva- (12 h t1/2) and rosuva (18 h)
metabolism of statins
hepatic
CYP3A4 for atorva, lova, simva
ADRs of statins
worst: myopathy
frequent: abd cramps, heartburn, diarrhea
less freq: elevated liver enzmyes, fatigue (? dec protein prenylation and ubiquinone production), dec in cognition
pregnancy: cat X (also in kids)
stages of statin myopathy and tx
earliest: mm ache, weakness (may be a/w inc CK levels)
mid: myositis, inflammation, acute pain
late: rhabdo, myoglobinuria, acute renal failure
may be related to low vit D levels, so vit D supplementation may reverse (even w statin continuation)
risk factors for statin toxicity
endogenous: age >65, low BMI/frailty, multisystem dz, thyroid d/o, metabolic mm dz, fam hx of mm sx, personal hx elevated CK
exogenous: heavy exercise, EtOH, drugs affecting CYP 450 system, consuming grapefruit juice
statin drug interactions
CYP 3A4 inhibitors inc levels of lova-, atorva-, and simvastatin: macrolides (not azithro), azole antifungals, CCBs, grapefruit juice
fibric acid derivatives (mostly gemfibrozil): inc serum level statin and risk of myopathy
statins and fibrates with non-CYP metabolism
rosuvastatin (90% non-CYP), pravastatin, pitavastatin
fenofibrate
ezetimibe
cholesterol-absorption inhibitor
metabolized to active glucuronide metabolite that localizes in intestinal brush border cells and inhibits absorption of dietary and biliary cholesterol (blocks transporter)
*may be inc risk myopathy when used w statins
cholestyramine
bile acid sequestrant - granules
colestipol
bile acid sequestrant - granules and tablet