Anti-hyperlipidemics Flashcards
Cholesterol absorbed through ______ transporter
NPC1L1
Reverse cholesterol transport
HDL accepts cholesterol from peripheral tissue - transported to liver
binds SR-B1 through ApoA1 in liver - cholesteryl esters delivered to hepatocytes
Familial Hypercholesterolemia
defects in LDL receptors = accumulation of LDL
Familial dysbetalipoproteinemia
defects/absence of ApoE = accumulation of VLDL and chylomicrons
Fibric Acid Derivatives
“FIBR”
Gemfibrozil
Fenofibrate
MOA Fibrates
PPAR activators Decreased TG Increased HDL Increased reverse cholesterol transport (HDL/SRB1) Increased FA oxidation
TX Fibrates
familial hypertriglyceridemia
familial combined hyperlipoproteinemia
Familial dysbetalipoproteinemia
Secondary hypertriglyceridemia
AE Fibrates
Rare
rashes
GI
Myopathy - increased risk w/statin - Gemfibrozil contraindicated
Bile Acid Binding Resins
“CHOL”
Cholestyramine
Colesevelam
Colestipol
MOA Resins
bind bile acids/salts
Force liver to increase bile acid synthesis - requires uptake of cholesterol
Increased LDL receptors
Lowers LDL but increases TG
TX Resins
Familial hypercholesterolemia in pts w/ statin resistance
drug of choice for children/pregnancy
AE Resins
increase TG - contraindicated in hypertriglyceridemia
bloating
constipation
MOA Niacin
inhibit VLDL synthesis/secretion
lowers VLDL/LDL/FFA
increase HDL
TX Niacin
All hypertriglyceridemia
All hypercholesterolemia
AE Niacin
cutaneous flushing/itching - secretion of prostacyclins from skin - pretreat w/NSAID Hyperuricemia hepatotoxic Statin induced myopathy Safest combo - niacin/fluvastatin Riskiest combo - niacin/lovastatin
MOA Ezetimibe
inhibit NPC1L1 = inhibit cholesterol uptake
Increase LDL receptor = decrease LDL
TX Ezetimibe
familial combined hyperlipoproteinemia
familial hypercholesterolemia
familial ligand-defective apoB
Statins
“STATIN”
Most potent - Atorvastatin, Rosuvastatin
Least potent - Fluvastatin
MOA statins
inhibit HMG CoA reductase reduce cholesterol increase synthesis of LDL receptor Increase LDL uptake from blood Decrease secretion of of VLDL
Pleotropic effects of statins
decrease coagulation decrease platelet activation increase endothelial function/progenitor cells increase NO decrease ROS decrease AT1 receptors Decrease VSMC proliferation decrease immune response decrease endothelin
AE Statins
Myopathy/myositis
rhabdomyolysis
liver toxicity
High potency statins - elevated ALT/AST - adaptive not toxic
True toxicity = elevated ALT/AST + bilirubin
TX Statins
Familial combined hyperlipoproteinemia
Familial hypercholesterolemia
Familial ligand-defective apoB
Familial dysbetalipoproteinemia
