Term
| What can hyperlipidemia cause |
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Definition
atherosclerosis, atherosclerosis associated conditions (coronary heart disease, ischemic cerebrovascular disease and peripheral vascular disease)
- too many lipids problem b/c inc plaque which causes inflammation |
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Term
| purpose of cholesterol/lipids |
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Definition
| vital structural component of cell membranes (precursor for steroids, bile, salts and steroid hormones) |
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Term
| where is cholesterol synthesized |
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Definition
| in the liver (involving HMG-CoA reductase)and from diet |
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Term
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Definition
| MAJOR dietary fat, main storage form of fuel, fatty acids released from TG in periods of reduced calorie intake. povide energy for muscle contraction and metabolic rxn |
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Term
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Definition
| glycerol backbone w/3 chains of fatty acids attached |
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Term
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Definition
| emulsification of fat by bile salts--> breakdown of TG by lipase--> formation of micelle, absorption into enterocytes--> lymphatic capillaries, thoracic duct, subclavian veins and inferior vena cava |
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Term
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Definition
| made in liver stored in gallbaldder, released into small intestine to absorb TG and fatty acids) |
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Term
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Definition
| formed in gut wall to take up stuff into interstinal epithelial cells (packages material into chylomicron and excretes into lymphatic system) |
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Term
| Absorption of glucose and AA |
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Definition
| absorbed from small intestine and transported into liver by the hepatic portal vein. (this is where many drugs are metabolized by 1st pass metabolism) |
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Term
| lipoprotein structure (LDL) |
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Definition
| core is hydrophobic, outside is phospholipid (monolayer) and cholesterol. the lipoprotein is stored in the middle but outside is hydrophilic. |
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Term
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Definition
biggest lipoprotein. (core lipid is dietary TG and cholesteryl esters (10:1), apoprotein are B-48, C, E, and A
-transport dietary lipids from GUT TO ADIPOSE tissue in liver. emulsified lipids by bile acids are combined w/proteins to form chylomicrons in gut wall, secreted into circulation and deliver TG to adipose tissue via action of LPL (lopcated in vasc. endothelial cells) converted to a cholesterol -rich chylomciron rementant. |
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Term
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Definition
| very low density lipoprotein (large but not dense) (core lipid is endogenous TG and cholesteryl esters 5:1) (apoproteins are C, B-100, and E) |
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Term
| intermediate density protein |
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Definition
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Term
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Definition
| (LDL) second to last in size (core lipid is cholesteryl ester and apoprotein is B-100) |
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Term
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Definition
| high density lipoprotein, smallest in size (core lipid is cholesteryl ester. apoproteins are A-1, A-2, C,E,and D) |
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Term
| primary action of chylomicron |
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Definition
| transports dietary lipids from gut to adipose tissue in liver (transports cholesterol to liver, muscle and adopocytes) |
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Term
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Definition
| golgi bodies in liver from VLDL from TG, cholesterol and protein. VLDL delivers TG to adipose tissue. VLDL transformed into IDL and LDL and contains a lot of cholesterol. LDL can undergo endocytosis and incorporated into lysosimes and can deliver cholesterol to nascent altheromas (atherlarscarosis, bringing cholesterol to tissue) |
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Term
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Definition
| small lipoproteins, secreted by gut and liver, large protin:lipid ratio- high density. HDL takes cholesterol from tissues and brings it back to liver or gives to LDL for transport to liver |
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Term
| 3 sources cholesterol is derived from |
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Definition
| 1.) Biosynthesis from acetyl-CoA, 2.)dietary cholesterol delivered by chylomicron remnants, 3.) endocytosis of LDL by LDL receptors |
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Term
| where and how are triglycerides and fatty acids formed |
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Definition
| triglycerides are formed in liver FROM fatty acids, fatty acids are derived from lipolysis of triglycerides in adipose tissue |
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Term
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Definition
| triglycerides, cholesterol and protein all packeged together by golgi bodies in liver to form VLDL which are then secreted into circulation |
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Term
| How do VLDL and HDL interact |
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Definition
| VLDL accept apoproteins C and E from HDL and return them to HDL as they deliver TGs (as fatty acids) to adipose and other tissues via action of lipoprotein lipase. Removal of apoproteins and triglycerides render the VLDL as IDL and LDL. |
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Term
| how is bile acid recycled back to liver |
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Definition
| bile acids excreted into duodenum via bile duct and returned to liver by portal circulation |
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Term
| how are bile acids made and where are they stored and how do they work |
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Definition
| in liver using cholesterol. stored in gallbladder. when you eat chyme arrives to small intestine and stim bile release from gallbladder. BILE SALTS EMULSIFY FATS! (bile acid sequesterants bind to bile acids in small intestine and form a complex so they can't go back into liver which reduces cholesterol in liver!) |
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Term
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Definition
| genetic or environmental factors. biochem defects in lipoprotein metabolistm. too much dietary intake of lipids, endocrine abnormalities, drugs that perturb lipoprotein formation or catabolism |
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Term
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Definition
| familial: defects in LDL receptor, defective apoB100 (dec affinity of LDL for the LDL receptor). Polygenic: most patients (85%) who don't have genetic cause |
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Term
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Definition
familial: inc hepatic TG synthesis, dec lipolysis of chylomicron and VLDL. Familial LPL deficiencey= elevated chylomicrons during infancy and impared removal of VLDL later in life. ApoC2 deficiency; defect in apoC2 (which activates LPL)
(IN GENERAL HYPERTRIGLYCERIDEMIA IS INC LEVELS OF CHYLOMICRON AND VLDL= INC LEVELS OF TGs) [they deliver TGs by breaking down TG into fatty acid which is done by LPL |
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Term
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Definition
| hypercholesterolemia and hypertriglyceridemia (inc in LDL (cholesterol) and VLDL (TG) |
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Term
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Definition
| ABC protein A1 deffect (gets cholesterol out of macrophages and artheloroma etc into HDL (cholesterol efflux pump)), LCAT (transports HDL from phospholipid to cholesterol which changes fluidity when not working) deficiency, ApoA1 deficiency, CETP deficiency. |
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Term
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Definition
caused by presence of alcoholism, DM or uremia or use of drugs like B-blockers, OC or thiazides. less commonly caued by hypothyroidism, nephrotic syndrome or obstructive liver diease
(HYPERLIPIDEMIA CAUSED BY OTHER DISEASE STATES, CONDITIONS OF DRUGS) |
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Term
| Atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin |
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Definition
| HMG- CoA reductase inhibitors |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
| cholesterol absorption inhibitor |
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Term
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Definition
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Term
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Definition
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Term
| what to HMG-CoA reductase inhibitors do |
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Definition
| decrease endogenous synthesis of cholesterol in liver |
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Term
| what do bile acid binding resins do |
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Definition
| block recycling of bile acids so liver can use up more cholesterol (dec cholesterol in blood) |
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Term
| what do cholesterol absorption inhibitors do |
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Definition
| block cholesterol absorption from small intestine. block dietary cholesterol and osme of cholesterol from bile salt |
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Term
| what do fibric acid derivatives do |
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Definition
| helps LDL, helps clear triglyceride |
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Term
| what does nicotinic acid do |
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Definition
| blocks synthesis of LDL in liver |
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Term
| HMG coA reductase inhibitor structure |
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Definition
| similar in structure to HMG coA so interferes w/binding of endogenous substrate to enzyme (HMG= 3-hydroxy-3methyl-glutaryl) |
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Term
| HMG co A reductase inhib in ring form and how do they work |
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Definition
| Lovastatin, pravastatin and simvastatin. They are PRODRUGS!! THe ring form is not active but they open up to become active |
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Term
| HMG-CoA reductase inhibitors MOA |
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Definition
| HMG co a reductase normally converts HMG-CoA to mevalonic acid (rate limiting step in synthesis of cholesterol) increases number of LDL receptors and delivers more LDL into liver. Reduces LDL in plasma and amt of cholesterol for fromation of VLDL. reductse inhib also reduce TG levels in plasma |
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Term
| HMG co a reductase inhib ADE |
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Definition
RHABDOMYOLYSIS (myalgia: muscle ache/weakness, myositis: muscle inflammation, pain and inc creatine kinase levels, Rabdomyolysis: muscle cells destroyed, release myoglobin into circulation which accumulates in kidney leading to kidney failure)
- GI upsed, nausea vomiting abdominal pain and diarrhea |
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Term
| HMG-CoA reductase inhibitor interactions |
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Definition
| P450 drugs, inc warfarin levels, inc myopathies when taken w/erythromycin, gemfibrozil or niacin. usually give at bedtime to inhibit nocternal cholesterol biosynthesis |
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Term
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Definition
| hmg co a reductase inhibitor should be taken in evening w/food to help w/absorption. crosses the BBB and can cause sleep disturbances |
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Term
| atorvastatin and rosuvastatin |
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Definition
| longer half lives can take at any time (hmg coa reduct. inhib) |
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Term
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Definition
| crosses BBB can cause sleep distur |
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Term
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Definition
| less likely to cause myopathy than other reductase inhib |
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Term
| indications for reductase inhib |
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Definition
| atherosclerosis, hypercholesterolimea, hypertriglyceridema, myocardial infarction prophylaxis |
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Term
| structure of bile acid binding resins |
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Definition
| binding resins are polymers of these structures repeating many times. |
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Term
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Definition
| remove cholesterol from body, eliminate catabolites from body, emulsify lipids/fat soluble vitamines in intestine. |
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Term
| MOA of bile acid binding resins |
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Definition
| resins bind to bile acids and form a complex which is excreted. this prevents enterohepatic recycling of bile acids and makes liver make bile acids from cholesterol. the liver inc LDL receptors which dec levels of LDL in blood. little effect on HDL and TG |
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Term
| ADE of bile acid binding resins |
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Definition
| GI constipation and sikin irritation (few ade b/c molecules big, arent' absorbed systemically) |
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Term
| bile acid-binding resins INTERACTIONS |
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Definition
| in gut cholestyramine and colestipol can bind with digoxin, thyroxin, warfarin and others so TAKE RESINS 2 HOURS B4 OR AFTER TAKING OTHER MEDS!!! (colesevelam is newer and isn't a problem. can be coadminishtered with most drugs) |
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Term
| how do bile acid binding resins work in terms of ions/properties |
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Definition
| they are ion exchangers w/hydrophobic properties. grab other things |
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Term
| indications for Bile acid resins |
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Definition
| diarrhea, hypercholesterolemia (colesevelam), digoxin overdose (colestipol) |
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Term
| cholesterol absorption inhibitor MOA |
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Definition
inhibit absorption of dietary cholesterol by blocking cholesterol/sterol transporter (niemann-pick C1-like 1 (NPC1L1) at brush border of small intestine
- reduces cholesterol absorption by about 50% |
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Term
| ADE of cholesterol absorption inhibitors |
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Definition
| diarrhea, HA, angioedema (INDICATED FOR HYPERCHOLESTEROLEMIA) |
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Term
| Fibric acid derivative MOA |
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Definition
| activate a gene transcription factor (peroxisome proliferator-activated receptor alpha (PPAR-a)) AGONIST FOR ppar alpha: increases expression of LPL (lower TG levels in blood), dec expression of inhibitor of LPL, inc expresison of enzymes that oxidize FA, inc expression of apoproteins A1 and A2, inc HDL levels; inc expression of cholesterol transport protein, inc expression of hepatic LDL receptors |
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Term
| Fibric acid derivatives ADE |
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Definition
| blood cell deficiencies, rhabdomyolysis, GI upset, rash or prutitis, diziness or HA |
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Term
| interactions- fibric acid derivatives |
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Definition
| combo of HMG-CoA reductase inhib and fibrates should be avoided or used w/great caution, can be given with cholestyrmine and colestipol but doses should be seperated by more than 2 hours b/c these resins reduce fibrate absorption |
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Term
| indications for fibric acid derivatives |
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Definition
| hyperlipoproteinemia, hypertrygliceridemia |
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Term
| nicotinic acid (niacin) MOA |
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Definition
| reduces lipolysis and free fatty acid transfer from adipocytes to liver, inhib GPCR Gi (dec cAMP), dec FFA availability reduce hepatic TG synthesis and VLDL secretion from liver [ blocks VLDL synthesis in liver |
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Term
| ADE of niacin (nicotinic acid) |
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Definition
| large doses needed to dec lipid levels and can cause flushing of skin, elevate transaminase levels and cause hepatitis, can cause GI distress (ulcer), can cause glucose intolerance and aggravate DM, avoid in pts with hepatic probs, peptic ulcers or uncontrolled DM |
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Term
| other considerations for nicotinic acid (niacin) |
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Definition
| best agent available for inc HDL inc 30-40%, lwers TG by 35-45%, reduces LDL by 20-30% |
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Term
| indications for nicotinic acid (niacin) |
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Definition
| hypertriglyceridemia, nutritional supplementation at lower doses. niacin is vitamin B essentially! |
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Term
| drug combos (ezetimibe/simvastatin and lovastatin/niacin) |
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Definition
| combo have additive effects on lowering cholesterol, ezetimibe blocks absorption, simvastatin inhib endogenous synthesis |
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Term
| What can fish oil, omega-3 fatty acids (lovazza) do in terms of cholesterol |
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Definition
| reduce TG in plasma and inc conversion to VLDL to LDL and inc HDL, dec thrombogenesis and stop platelet aggregation, slow atherosclerosis, inc NO vasodilation and reduce arrhythmia |
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