KG - Pharm 2 Exam 2, Hyperlipidemia Flashcards
list bile acid binding resins
Cholestyramine
colestipol
colesevelam
bile acid binding resins MOA
- bind bile acids and prevent intestinal reabsorption
- decreases bile acids, which increases uptake of LDL (lower LDL decreases plasma cholesterol)
bile acid binding resins indications/therapeutic effects
- effective WHEN LDL IS ELEVATED
- NO EFFECT in HOMOZYGOUS familial hypercholesterolemia (no functional LDL receptors)
- NO EFFECT HYPERTRIGLYCERIDEMIA (may increase VLDL)
bile acid binding resins pharmacokinetics
- not absorbed
- take w/ meals (need to produce bile for effect)
bile acid binding resins adverse effects
- safe!
- CONSTIPATION, BLOATING
- steatorrhea w/ cholestasis
- rare = gallstones (esp obese pts)
- rare = HYPERPROTHROMBINEMIA due to Vit K malabsorption
- can impair absorption of certain drugs (digitalis, thiazides, statins, tetracycline, thyroxine, aspirin)
niacin MOA
- lowers VLDL/LDL by INHIBITING VLDL SECRETION
- inhibits hepatic cholesterologenesis
niacin indications/therapeutic effects
- increased clearance LDL pathway
- INCREASED LEVELS HDL (most effective agent)
- most effective for hypercholesterolemia
niacin pharmacokinetics
- oral
- renal excretion
- doses = gram range (vitamins = mg)
niacin adverse effects
- mild effects
- cutaneous VASODILATION, warm sensation, pruritis, dry skin
- NAUSEA & ABDOMINAL DISCOMFORT
- IMPAIRS GLUCOSE INTOLERANCE
- hyperuricemia
- rarely, but possible HEPATOTOXICITY
what are two hallmark effects of niacin?
VASODILATION & IMPAIRS GLUCOSE INTOLERANCE
list of statins (HMG CoA Reductase Inhibitors
Atorvastatin fluvastatin lovastatin pravastatin simvastatin rosuvastatin
statins MOA
- active forms = analogs of HMG CoA reductase
- reduce plasma LDL by INHIBITING REDUCTASE TO INCREASE HIGH AFFINITY LDL RECEPTOR
statins indications/therapeutic effects
- DECREASE LDL - MOST EFFECTIVE DRUG!
- decr plasma triglycerides
- increase HDL
- DECREASE CRP in pts w/ CHD
- enhance production of NO
- INCREASE PLAQUE STABILITY
- DECREASE LIPOPROTEIN OXIDATION
- DECREASE PLATELET AGGREGATION
when are statins most effective?
when LDL IS ELEVATED!
statins pharmacokinetics
- high first pass
- liver metabolism
- GI excretion
- GIVE IN THE EVENING (diurnal pattern cholesterol synthesis)
which two statins are inactive?
LOVASTATIN & SIMVASTATIN - must be hydrolyzed to active form
statins - adverse effects
- INCREASED levels serum aminotransferase (reversible)
- LIVER DAMAGE in alcoholics, pts w/ liver probs
- SERUM Cr KINASE ACTIVITY - associated w/ phys activity
- Rhabdomyolysis
statins contraindications/precautions
- contraindicated in PREGNANCY
- ACTIVE HEPATIC DZ
- p450 inhibitors (increase statin concentration)
- p450 activators (decrease plasma concentrations of statins
which fibrate inhibits metabolism of statins?
Gemfibrozil
fibrates MOA
PPAR alpha ligand - upregulates LPL and other genes involved in fatty acid oxidation
list fibrates
gemfibrizol
fenofibrate
fenofibric acid
fibrates indications/therapeutic effects
- increase LPL –> incr catabolism VLDL
- DECREASE TRIGLYCERIDES by lowering VLDL conc
- decrease cholesterol by inhibiting hepatic cholesterologenesis
fibrates adverse effects
- skin rashes, GI symptoms, arrhythmias, hypokalemia, myopathy
- incr blood aminotransferases, alkaline phosphatase
- INCREASED INCIDENCE CHOLELITHIASIS OR GALLSTONES = HALLMARK EFFECT
- potentiate effect warfarin
- may increase LDL
Ezetimibe MOA
selectively BLOCKS INTESTINAL ABSORPTION of cholesterol and phytosterols
Ezetimibe indications/therapeutic effects
- moderate decr LDL
with which drug would you combine Ezetimibe to get synergistic effects?
STATIN!
- can produce reductions 25% beyond if using drug alone
Ezetimibe pharmacokinetics
- metabolized by liver
- enterohepatically recirculated
Ezetimibe adverse effects
NONE!
drug used for high cholesterol?
cholestyramine
cholestipol
ezetimibe
drug used for high triglycerides?
gemfibrozil
drug used for high cholesterol AND triglycerides?
statins + niacin, ezetimibe
