Hyperlipidemia Flashcards
Hyperlipidemia leads to
pancreatitis and atherosclerosis
*atherosclerosis is leading cause of death for both genders in US
what is familial hypercholesterolemia
LDL receptor deficiency resulting in increased LDL
*can be heterozygous or homozygous
LDL is increased by
cholesterol, sat fat, trans fat
TAG are increased by
total fat, alcohol, excess calories
dietary changes should also be the first go to for HTN pt except in pt with
coronary or PVD,
family hypercholesterolemia/hyperlipidemia
if on wt. loss regimen, when should you check cholsterol
after stabilized wt for 1 mth bc chol levels low during wt loss
what are the bile acid binding resins
cholestyramine, colestipol, colesevelam
*note: cholestyramine decreases Digoxin toxicity by decreasing GI absorption
how do bile acid binding resins work
they bind bile acids = prevent intestinal reabsorption
this increases LDL receptor expression thus increasing uptake of plasma LDL to make more bile acids.. the decreased LDL will decrease plasma chol
when do you use bile acid binding resins?
whenever LDL is high
- but not effective in HOMOzygous familial hypercholesterolemia bc no functional LDL receptor
- not effective in hypertrig bc may increase VLDL
When shouldn’t you take bile acid resins
if hypertriglyceridemia (may increase VLDL) if homozygous familiy hypercholesterolemia
How should you take bile acid resins
with meals bc need bile production for effect
*not absorbed
what are the safest hypolipidemics
bile acid binding resins bc not absorbed
common side effects of bile acid binding resins include
- *constipation and bloating (hallmark)
- steatorrhea if pt has cholestasis
- rare: gallstone formation in obese, hypoprothrombinemia due to vit K malabsorption
bile acid binding resins may impair absorption of ….?
certain (acids or fat soluble) drugs such as digitalis, thiazides, statins, tetracycline, thyroxine, ASA
how does niacin (b3) work?
lowers plasma VLDL and LDL by INHIBITING VLDL SECRETION
*also inhibits hepatic cholsterologenesis
thus most effective for hyperchol and to increase HDL
indications for Niacin tx
increase clearance in LPL path –> dec VLDL
increase HDL (most effective agent)
most effective in hyperchol
Pharmacokinetics of Niacin (absorption, secretion, dosage)
ORAL
RENAL EXCRETION
dose in g range
Adverse effects of Niacin
generally mild but include
- CUTANEOUS VASODILATION, warm sensation, pruritus, dry skin (PG dependent so take ASA before)
- Nausea and abdominal discomfort
- may ^ liver enzymes, **IMPAIRS GLUCOSE TOLERANCE
- hyperuricemia
- may cause severe hepatotoxicity
How do statins work
inhibitors of HMG coA reductase
*analogs of HMG coA reductase intermediate in mevelonate synthesis
What do statins do to improve hyperlipidemia
reduce LDL (inhibiting reductase causes increase in LDL receptor affinity) *most effective at reducing LDL *also decrease TAG, increase HDL
other beneficial effects of statins include
- decrease CRP, lipoprotein ox, platelet aggregation
- increase plaque stability
- enhance NO production
when are statins most effective
when LDL is elevated
once again.. statins do what?
decrease LDL Decrease TAG increase HDL decrease CRP, lipoprotein ox, platelet aggregation increase plaque stability, NO production
Pharmacokinetics of Statins
high first pass
metab by liver, GI excretion
*give at night bc diurnal pattern of chol syn
what are some adverse effects of statins
increase serum aminotransferase (reversible)
- may produce liver damage in alcoholics or pt with pre-existing liver problems
- increase serum creatine kinase in phys activity
- rhabdo.. myoglobinuria, renal shutdown (rare)
when shouldn’t you prescribe statins
preg (catX)
active hepatic dz (caution alcoholics, liver dz)
P450 inhibitors increase concentration (grapefruit, macrolide, cyclosporine, verapamil)
P450 activators decrease (phenytoin, barbiturates, rif)
*gemfibrozil inhibits their metab
don’t combine statins with
P450 inhibitors (increase statin) P450 activators (decrease statin) fibrates (inhibit statin metab)
how do fibrates work
they are PPAR alpha ligands that UPREGULATE LPL and other genes in FA ox
when should you prescribe fibrates
increase LPL, increase VLDL catabolism = DECREASE TAG by lowering VLDL
*also decrease chol
when are fibrates effective
hypertrig
adverse effects of fibrates include
rashes, GI sx, arrhythmias, hypokalemia, myopathy, increase aminotransferase and alk phos
- increase CHOLELITHIASIS/GALLSTONES
- potentiate warfarin action
- inhibit statin metab
- may increase LDL in some pt with combined hyperlipidemias
MOA of ezetimibe
selectively blocks intestinal absorption of CHOL
use of ezetimibe
decrease LDL (moderate) **combine with statin = reduction of LDL up to 25% beyond statin alone
how is ezetimibe metab
by liver then enterohepatically recirculated
adverse effects of ezetimibe
none so far
HMG CoA reductase effect
*decrease LDL, increase HDL, decrease TAG
Bil acid binding resins action
decrease LDL
Fibrate action
decrease TAG
Niacin action
decrease LDL, Increase LDL, decrease TAG
if high chol…
give cholestyramine, ezetimibe
if high TAG
give fibrate
if high chol and high TAG
statin and niacin, ezetimibe
