Term
| Cholestyramine, Colestipol |
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Definition
bile acid binding resins
MOA: bind cholesterol-containing bile acids and prevent reabsorption, increase clearance, increased hepatic metabolism of cholesterol to bile acids (regulated by neg feedback), decreased hepatic cholesterol content, upregulation of hepatic LDL receptors
PK: negligible systemic bioavailaility, must be taken with meals to be effective
CI: familial hypercholesterolemia, combo therapy for familial combined hyperlipoproteinemia
AE: GI disturbances (constipation and abdominal discomfort)
DI: may reduce absorption of vitamins and drugs taken at the same time -> patients should take other drugs at least 1 hours before or at least 2 hours after resin |
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Term
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Definition
cholesterol absorption inhibitor
MOA: localizes and acts at the brush border of small intestine -> inhibit absorption of cholesterol (decrease delivery of intestinal cholesterol to liver, decrease hepatic cholesterol stores, increase clearance of cholesterol from blood
CI: monotherapy-cholesterol lowering is limited (reduced uptake of dietary cholesterol but upregulates hepatic cholesterol synthesis), combo with HMG CoA reductase inhibitors -> 20% additional decrease (allow reduction of statin dose while achieving cholesterol-lowering goal) |
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Term
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Definition
fibrates/cholesterol absorption inhibitor
-ligand for PPAR-alpha
MOA: decrease apoB synthesis, decrease VLDL synthesis, decrease apoC-III synthesis, increase apoA-I and A-II synthesis, increase LPL synthesis, increase catabolism of TRLs -> decrease TG (major effect) and increase HDL
PK (fenofibrate): more potent than gemfibrozil, longer ½ life, renal and fecal excretion
PK (gemfibrozil): well absorbed when taken with meal, shorter ½ life than fenofibrate, most excreted unchanged in urine
CI: dysbetalipoproteinemia, hypertriglyceridemia
AE: GI disturbances, skin rashes, MYOPATHY, arrythmias, fatigue
Contra: renal or hepatic dysfunction
Preexisting gallbladder disease, hypersensitivity
DI: potentiate effects of coumarin and indanedione anticoagulants(reduce anticoagulant doses and monitor prothrombin levels), myalgias and rhabdmyolysis for combo of gemfibrozil and HMG CoA reductase inhibitors |
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Term
| Avostatin, Lovastatin, Simvastatin, Rosuvastatin |
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Definition
HMG CoA reductase inhibitors
MOA: forms analog of intermediate in conversion of HMG CoA to mevalonic acid, competitively inhibit HMG CoA reductase (rate-limiting and committed step of cholesterol synthesis), hepatic LDL receptors are upregulated -> LDL and IDL clearance increased; inhibition of apoB-100 synthesis, inhibition of TRL synthesis and secretion, improve endothelial function and stabilize atherschlerotic plaque
-atovastatin and simvastatin reduce LDL in homozygous familial hypercholesterolemia
PK: oral bioavail differs between statins; lovastatin and simvastatin admin lactone form (prodrugs); extensive 1st pass metabolism, bound to protein; lovastatin, simvuastatin, atorvastatin -> CYP3A4 (affected by grapefruit juice)
CI: most commonly used drugs for hypercholesterolemia (monotherapy or combo therapy), preservation of bone mineral density, increase osteoblast differentiation and activity
AE: generally well tolerated, hepatotoxicity, myopathy -> rhabdomyolysis and renal failure (risk is increased in combo therapy with fibric acid derivatives and other drugs that inhibit CYP3A4)
Contra: pregnancy, liver disease, major illness or trauma
DI: lovastatin and simvastatin potentiate action of coumarin anticoagulants |
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Term
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Definition
-vit B3, used in synthesis of NAD and NADP, inhibits adipocyte adenyl cyclase
MOA: decrease TG synthesis, decrease VLDL secretion, decrease apoA-1 clearance, increases LDL, increases VLDL clearance -> decreased TG, decreased LDL, decreased Lp(a), increased HDL (major effect)
PK: rapidly absorbed, sustained-release tablets, distributes throughout body, excreted by kidneys, high doses required for lipid lowering
CI: hypertriglyceridemia w/ elevated LDL-C and low HDL-C; combo therapy w/ resins for familial hypercholesterolemia, any pt whose LDL-C is controlled but HDL-C is low; combo therapy with resin and statin -> reduce LDL-C by 70% or more
AE: CUTANEOUS VASODILATION -> flushing and pruitis (take aspirin prior to reduce rxn), nausea and diarrhea; may precipitate abnormal liver function, hepatoxicity, glucose intolerance, peptic ulcers, gout
Contra: peptic ulcers, glucose intolerance, gout, hepatic function should be monitored
DI: induce hypotension in combo with anti-HTN drugs |
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Term
| Omega-3 Fatty Acid Ethyl Ester |
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Definition
MOA: adjunct to lipid-lowering diet to reduce TGs in adults with severe hypertriglyceridemia, reduce hepatic TG synthesis and increase plasma lipoprotein lipase activity
Contra: hypersensitivity, fish allergies |
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