hyperlipidemia

Question 1

SE and contraindications of resins

Answer 1

• safe since they aren’t systemically absorbed (only one prescribed for children)
• bloating, constipation
• dyspepsia
• gritty unpleasant taste
• resins bind other drugs and prevent their absorption (ie: cardiac glycosides and anticoagulants)
• malabsorption of fat soluble vitamins
• contrandicated in PTs with hypertriglyceridemia

Question 2

Nicotinic Acid (Niacin) mechanism

Answer 2

• decreases hormone-sensitive lipase in adipose tissue –> decrease FFA –> decreased synthesis of TG in liver –> decreased liver VLDL synthesis –> decreased LDL
• increases ApoA1 –> increases HDL
• best agent available for increasing HDL
• lowers TG as effectively as statins and fibrates
• **especially useful for PTs with hypertriglyceridemia and low HDL

Question 3

SE and contraindications of statins

Answer 3

• hepatic toxicity (1% –> check LFTs)
• myopathy –> contraindicated with fibrates (increased risk of myopathy)
• contraindicated in pregnant and nursing women
• increases intestinal cholesterol absorption (take with Zetia)
• benefits: reduce LDL oxidation, cardioprotective effects and counteract osteoporosis

Question 4

pharmacokinetics of statins

Answer 4

• lovastatin and simvastin are lactone produgs that must be modified in liver to active (ring-open) forms
• plasma concentrations peak in 1-4 hours
• atorvastatin (lipitor) and rosuvastatin (crestor) have longer t1/2 and can be administered 1/day
• all other statins should be taken in pm since cholesterol synthesis is maximal between 12-2am

Question 5

SE of fibrates

Answer 5

• gallstones and GI SEs
• myositis (can’t prescribe with statin)
• potentiate the action of oral coagulants

Question 6

bile acid sequestrants (resins)

Answer 6

• cholestyramine, colestipole and colesevelam
• positvely charged to bind anionic bile acids –> bound bile acids are excreted in stool (prevent their reabsorption)
• depletes liver bile acid pool –> increased hepatic bile acid synthesis –> decreased hepatic cholesterol –> production of LDL receptors –> increases LDL clearance –> lowers LDL
• slight increase in TG and HDL

Question 7

combo tx

Answer 7

• statin + ezetimibe lower cholesterol by 65%
• statin + resin + niacin lower cholesterol by 70-75%
• combo of statin and fibrate increases risk of myosits
• ezetimibe + simvastatin = Vytorin
• niacin + lova/simvastatin = Advicor/Simcor

Question 8

Exogenous Lipid Transport

Answer 8

cholesterol and TG are ingested and emulsifed in intestines by bile acids –> combine with proteins to form chylomicrons in gut wall –> chylomicrons secreted into circulation –> endothelial/plasma LPL cleaves into TG and FFA –> delivery to tissues –> remaining cholesterol-rich chylomicron remnant delivers cholesterol to liver

Question 9

endogenous lipid transport

Answer 9

• liver synthesizes VLDL from TG, cholesterol and proteins –> VLDLs deliver TG to adipose tissue –> converted to IDL and LDL –> LDL delivers cholesterol to peripheral tissues and atheromas
• LDL also delivers cholesterol to liver –> apoB100 binds LDL-R –> LDL-R recycled while LDL is hydrolyzed into free cholesterol
• intracell cholesterol –> decreases HMG-CoA reductase, activates ACAT (esterifies cholesterol for storage) and inhibits transcription of LDL-R

Question 10

HMG-CoA Reducatse Inhibitors (mech)

Answer 10

• statins
• reversible competitive inhibitors of HMG-CoA Reducatse inhibitor –> prevent synthesis of cholesterol –> lowers VLDL (and TG)
• activates SREBP (TF) to upregulate the synthesis of LDL receptors –> lowers LDL

Question 11

Ezetimibe

Answer 11

• Zetia
• inhibits cholesterol absorption from entercytes in SI
• only lowers LDL a little bit as monotx
• SE: enhances cholesterol biosynthesis –> synergistic affect with statins (Vytorin)

Question 12

fibrates (mechanism)

Answer 12

• clofibrate, gemfibrozil, fenofibrate, ciprofibrate,bezafibrate
• bind to PPARalpha and increase expression of lipoprotein lipases (LPLs) –> enhances clearance of TG-rich lipoproteins by liberateing FFA to be stored in adipose tissue or used for energy (loweres VLDL and TG)
• inhibit apoCII expression –> enhances clearance of VLDL (lowers VLDL and some LDL)
• stimulate apoAI and apoII expression –> increases HDL
• used for severe hypertriglyceridemia

Question 13

Niacin SE and contraindications

Answer 13

• flushing, itching (PGE mediated), skin rashes, acanthosis nigrans
• dyspepsia and reactivation of peptic ulcer disease
• serious complications: hepatotoxicity, hyperglycemia and hyperuricemia
• contraindications: PTs with diabetes mellitus or gout