Lipid disorders Flashcards
define atherosclerosis
abnormal deposition of cholesterol in arteries
3 sites to decrease cholesterol
decrease GI uptake
decrease LDL levels
decrease endogenous cholesterol synthesis
how can you decrease GI uptake of cholesterol
decrease dietary intakes, reabsorption of bile acids, and absorption of cholesterol
what class of drugs are the statins, what does that do
HMG-CoA reductase inhibitors which is the rate limiting step in cholesterol synthesis causing an increase in LDL receptors
what effect do the statins have
decrease LDL levels and triglyceride levels
when should you give statins
at night because that is when you are not eating and the body would be synthesizing its own cholesterol
adverse effects of statins
myalgia, muscle weakness
increase inplasma aminotransferase
first pass metabolism
statins contraindicated in
pregnancy
why is grapefruit juice bad
inhibits CYP3A4
which will result in increase of statin bioavailability
what strength of stain should be used
10mg, any increase doesnt result in much more efficacy
example of cholesterol absorption inhibitor
ezetimibe
how do cholesterol absorption inhibitors work
inhibit cholesterol transport protein NPC1L1, inhibiting dietary and biliary cholesterol absorption
where does ezetimibe work
at the intestinal brush border
what is the downfall of cholesterol absorption inhibitors
less cholesterol absorbed from the gut so there is an increase in the amount that the liver produces
potential side effects of ezetimibe
myalgia
hepatitis
rhabdomyolysis
acute pancreatitis
examples on bile binding resins
cholestyramine
colestipol
colesevelum
how do bile acid binding resins work
anion exchange resin that binds to bile in intestinal lumen and doesnt allow it to be recirculated
how does preventing bile reabsorption decrease cholesterol
liver has to increase LDL receptors to take up cholesterol to synthesize new bile salts and synthesize de novo cholesterol
adverse effects of bile acid binding resins
increase VLDL decrease absorption of fat soluble vitamines nausea, constipation unpleasant taste/texture absorption of drugs altered
why combine statin and ezetimibe
ezetimibe decrease cholesterol uptake in the gut but mechanisms increase synthesis in the liver. the HMGCoA reductase inhibito blocks the increased synthesis in the liver
reasons of failure to achieve target LDL-C
poor adherence high baseline LDL-C high cholesterol diet or absorption variable statin response inability to tolerate higher dose statins
what is the new expensive therapy
inject human monoclonal antibody to PCSK9 to increase LDL receptors on the liver
how does the PCSK9 antibody work
causes the LDL receptor to be recyled rather than degraded and then be expressed at the surface
potential sites to decrease triglycerides
decrease dietary triglycerides
increase lipoprotein lipase activity
decrease VLDL secretion from the liver
non pharm to decrease triglycerides
eat more fiber
examples of fibric acid derivatives
fenofibrate
gemfibrozil
fibrates mechanism
increased VLDL clearance due to increased lipoprotein lipase activity
decreased VLDL secretion
side effects of fibrates
flu like
muscle crampls
myopathy
contraindications of fibrates
hepatic or renal dysfunction
oral anticoagulants
cyclosporine
how do fibrates increase the amount of lipoprotein lipase
bind to receptor and increase transcription of LPL
what effects does nicotinic acid have
low doses increases HDL levels
higher doses decrease VLDL and triglyceride levels
how does niacin decrease hepatic VLDL production
activates niacin receptors in adipocytes decreases cAMP which decrease triglyceride hydrolysis causing less fatty acid in circulation to be taken up by liver(which means less converted to TG and secreted as VLDL)
how does niacin increase VLDL clearance
increases lipoprotein lipase activity
adverse effects of niacin
skin flushing and itching
increase aminotransferase or alkaline phosphatase
contraindications of niacin
peptic ulcer
diabetes due to glucose intolerance
