Term
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Definition
| Elevated plasma cholesterol and/ or TAGs, or a low HDL level. Can be genetic or secondary |
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Term
| What is most closely related to cardiovascular mortality? |
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Definition
| Elevated LDL cholesterol > decreased HDL cholesterol. Hypertriglyceridemia is an independent risk factor (?) |
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Term
| What is the Fredrickson classification of familial hyperlipidemia? |
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Definition
| Phenotypic grouping based on lipoprotein elevation |
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Term
Type 1
Familial Hyperchylomicronemia |
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Definition
| Increased Chylomicrons; def of LPL or apoCII, Rare |
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Term
Type 2 A Familial Hypercholesterolemia
Type 2 B Familial combined Hyperlipidemia |
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Definition
Increased LDL; Def or defective LDL R.
Increased LDL & VLDL; overprod of VLDL by liver; Relatively common |
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Term
Type 3
Familial dysbetalipoproteinemia |
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Definition
| Increased IDL; abnormal apoE |
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Term
Type 4
Familial hypertriglyceridemia |
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Definition
| Increased VLDL; overprod of impaired metabolism of VLDL; Relatively common |
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Term
Type 5
Familial mixed hypertriglyceridemia |
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Definition
| Increased chylomicrons and VLDL; overprod or decreased metabolism of VLDL & chylomicrons |
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Term
| What is the cause for secondary hyperlipidemia? |
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Definition
| Saturated fat, cholesterol & trans FAs; alcohol (increases FA synthesis -> VLDL); Diabetes as insulin normally supressed VLDL production. NB that apoCIII levels are also increased due to insulin resistance in DM type 2, this allows decreased catabolism of chylomicrons & VLDL; hypothyroidism |
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Term
| What are the common secondary causes of hyperlipidemia? |
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Definition
Hypertriglyceridemia -
Hypercholesterolemia - |
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Term
| What can high TAGs cause? |
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Definition
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Term
| What is Friedewald formula? |
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Definition
| LDL = TC - [HDL + (TAG/5)], only valid if TAGs are <400mg/dL AND pts are fasting for 10 hrs |
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Term
| Why cant lipid-regulating drugs be stopped? |
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Definition
| Plasma lipoproteins levels return to pre-treatment in 2-3 wks |
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Term
| What are the five classes of drugs used to Tx hyperlipidemia? |
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Definition
Statins
Niacin
Bile acid-binding resins
Fibric acid derivatives
Cholesterol absorption inhibitors |
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Term
| What are the statins a.k.a HMG-CoA Reductase Inhibitors? |
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Definition
Simvastatin (oldest)
Fluvastatin
Lovastatin
Pravastatin
Atorvastatin (Potent and decrease TAGs)
Rosuvastatin (Potent and decrease TAGs) |
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Term
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Definition
| They are analogue of HMG, thus competitive inhibitors. |
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Term
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Definition
| 3 Acetyl-CoA come together |
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Term
| Which two statins are prodrugs? |
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Definition
| Simvastatin & Lovastatin, they are inactive lactones that in the GIT are hydrolyzed to the active beta-hydroxyl derivatives |
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Term
| What are the DOC for lowering LDLs? |
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Definition
| Statins. NB that these may even help homozygous familial hypercholesterolemia pts via secondary mechanisms (imporving endothelial function thereby reducing inflammation then thus decrease platelet aggregation & levels of C-reactive protein) |
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Term
| What are two A/Es of statins? |
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Definition
| Elevation of aminotransferases w/out liver toxicity; Myopathy & rhabdomyolysis (-> renal injury) are rare but CK levels shud be monitored. |
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Term
| Which rx do u know that works on all lipid parameters? |
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Definition
| Niacin (nicotinic acid). NB that its the most effective agent to increase HDL and is the only agent to reduce Lp(a) |
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Term
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Definition
Gi coupled in adipocytes which inhibits hormone-sensitive lipase, thus a lack or raw products to make VLDLs in the liver but on top of that in the liver niacin prevents esterification of FA's thus furthering its effect, now decreased VLDLs mean decreased LDLs.
Niacin also increases LPL activity thus clearing VLDL and chylomicron TAGs.
It also decreases the catabolism of HDL thus increasing those numbers.
Fibrinogen levels drop and tissue plasminogen activator increase (?) |
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Term
| What are the A/Es of niacin? |
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Definition
| Intense cutaneous flushing upon starting or increasing dose, mediated by prostaglandins thus prevented by giving asprin 30 mins prior; Pruritis, rashes, dry skin & acanthosis nigricans have been reported. Most severe are hepatotoxicity & hyperglycemia (from induced insulin insensitivity), elevates uric acid levels -> gout |
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Term
| What are the two Fibrates u know? |
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Definition
Gemfibrozil
Fenofibrate
NB that they are derivatives of the 1st generation fibric acid Clofibrate |
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Term
| What receptor do Fibrates work on? |
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Definition
| PPAR-alpha, a nuclear transcription receptor, found mainly in the liver and brown adipose tissue. This receptor regulates gene involved in: lipid & glucose metabolism, endothelial function & inflammation. |
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Term
| What are Fibrates used for? |
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Definition
| It lowers TAGs (and thus VLDLs) & increases HDLs (moderately). It does the former via: increasing muscle cell LPLs, decreasing hepatic expression of apoCIII (?) and increasing hepatic FA oxidation. |
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Term
| What are some of the A/Es of Fibrates? |
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Definition
1) Mild GI distrubances
2) Myositis esp pt w/ renal insufficiency; rhabdomyolysis is rare
3) Lithiasis cause of increased biliary cholesterol secretion -> gallstones (High risk in women, obese pts & native americans) |
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Term
| How come with fibrate use in pts with combined hyperlipidemia there can be a TAG reduction but LDL will increase??? |
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Definition
| Because there is only a modest decrease in LDL if this Rx is used to Tx 2B (combined hyperlipidemia) then LDLs increase (why?) |
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Term
| Which grp of Rxs do you know that works on dysbetalipoproteinemia? |
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Definition
|
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Term
| What are the bile acid-binding resins? |
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Definition
| Cholestyramine, Colestipol, Colesevelam (has less A/Es and no interactions w/ Rxs) |
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Term
| Which Rx do u know that will work on hyperlipoproteinemias but might increase VLDLs? |
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Definition
| Resins, are insoluble in water and have a high MW thus not absorbed or metabolised in the intestine |
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Term
| What is the DOC in children and women who are planning on becoming pregnant? |
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Definition
Resin. However they are limited by their A/Es: bloating, nausea, cramping and constipation.
They may increase TAGs and thus contraindicated in hypertryglyceridemia (?). NB that they also impair absorption of KEDA vitamins |
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Term
| Which grp of Rxs compliment the Statins? |
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Definition
| The Cholesterol absoption inhibitors like Ezetimibe |
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Term
| Which transport protein does Ezetimibe inhibit? |
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Definition
| NPC1L1 in jejunal enterocytes. This receptor is bound to and internalized. Cholesterol absorption can be lowered by 50% |
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Term
| What is the very artherogenic lipoprotein u know? |
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Definition
| Chylomicron remnants, thus w/ Ezetimibe u'll be able to reduce the atherogenesis directly |
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Term
| What are the A/Es with Ezetimibe? |
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Definition
| Small incidence of reversible impairment of hepatic function, this increases slightly when given with statins; myositis is rare |
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Term
What are the w-3 FAs?
NB that they are found over the counter as FA ethyl esters in capsules |
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Definition
| EPA & DHA which are aka fish oils -> reduce plasma TAGs (less syn and more oxidisation in liver) in a dose-dependent way. Long term use may even increase HDL. There may be an artifact increase in LDL |
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Term
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Definition
| Its a Ethyl ester of w-3 FAs but given to pts w/ very high (>500mg/dL) TAG levels |
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Term
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Definition
Statins - DOC to lower LDLs & only atro & rosu decreease TAGs by 40%
Fibrates - increase HDL and decrease TAGs (like niacin), dysbeta (?)
Resins - may increase TAGs, DOC 4 preg & and children
Ezetimibe - Compliments statins
Niacin - increase HDL and decrease TAGs (like fibrates) |
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Term
| What is Vytorin & Advicor? |
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Definition
Vytorin - Ezetimibe + sim
Advicor - Extended release niacin + Lo |
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Term
| Which Rx combos increase incidence of myopathy & rhabdomyolysis? |
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Definition
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Term
| What category do the different antihyperlipidemic Rxs fall under in pregnancy? |
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Definition
B - Colesevelam (Colesevelam)
C - Fibrates (Gemfibrozil, Fenofibrate), Niacins, Other Resins, Ezetimibe (cholesterol absorption inhibitor)
X - Statins |
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