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89 Cards in this Set
- Front
- Back
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hyperlipidemia is an elevated plasma levels of:
a. cholesterol b. cholesterol esters c. triglycerides d. phospholipids e. all of the above f. only b and c g. a,b, and c |
answer: E
But most important are cholesterol esters and triglycerides in contributing to heart disease |
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hyperlipidemia is the major cause of atherosclerosis and associated conditions including:
a. coronary heart disease b. ischemic cerebrovascular disease c. peripheral vascular disease d. a and c e. all of the above |
answer: E
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which of the following cause endothelial cell injury:
a. smoking b. increase physical activity c. increase saturated fat d. decrease vitamins intake e. all of the above f. a, b, and c |
answer: F
decrease vitamins will cause LDL oxidation |
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which of the following can cause LDL oxidation?
a. increase salt and trans fat b. smoking c. decrease physical activity d. decrease omega 6/ omega 3 ration e. all of the above f. all except d f. a,b, and |
answer: F
increase omega 6/ omega 3 ratio will increase LDL oxidation. That's why it is recommended to take fish oil. |
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apoAI is a component of?
a. vldl b. hdl c. ldl d. idl e. b and d f. all of the above |
answer: b
apoA-I sysnthesized in the liver and intesting: structural in HDL; LCAT cofactor; ligand of ABCA1 receptor; reverse cholesterol transport |
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apo B-48 is structural protein of
a. vldl b. ldl c. chylomicrons d. idl |
Answer: c
apoB-48 is synthesize in the intestine and structural proteins of chylomicrons |
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______ synthesis in the liver and it is a lpl cofactor:
a. apoC-II b. apoC-III c. apoB-100 d. apoE |
answer: A
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apoC-III function:
a. LCAT activator b. lpl cofactor c. modulates receptor binding of remnants d. ligand for ldl receptors |
answer: C
apoC-I is LCAT activator apoC-II is lpl cofactor apoE: ligand for LDL receptor |
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what are the components of chylomicron?
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APOC-II, apoE, apoB-48 inside; cholesteryl ester and TG inside.
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_____, ______, ______ act to inhibit formation of TG
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NPC1L1, ACAT, and MTP
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DGAT2 can make TG from _____ + _______.
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NEFA + DG
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ApoB-48 can be recognized by LDLR. True/False
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False
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Explain apoB dependent and apoB independent routes of processing dietary cholesterol.
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Look it up.
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If a person has ABCA1 deficiency, what most likely happen to his HDL?
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decrease HDL because ACA1 is a cholesterol transporter, it transports cholesterol in HDL.
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what is the function of ABCG5/G8?
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pump out plant sterols (unesterified cholesterol which from micelle).
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Which of the following is not involved in apoB dependent routes?
a. DGAT2 b. UC c. ABCA1 d. NPC1L1 |
Answer: C
ABCA1 involves in transport cholesterol in HDL and it is apoB independent. |
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what is the function of ACAT?
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Answer: it is in the ER and converts UC to CE, a component of chylomicron in the apoB dependent routes
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what is the function of APC1L1?
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Answer: APC1L1 is a cholesterol transporter, involves in the apoB dependent routes and transport UC into the ER.
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What is the function of DGAT2?
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Answer: it acylates diacylglycerols to TG in the ER, involves in the apoB dependent routes.
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What is the function of MTP?
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Answer: MTP tranfers TG to apoB particles in the ER. Involves in the apoB dependent routes.
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What is the product of apoB dependent route?
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Answer: Chylomicron
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What is the product of apoB independent route?
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Answer: HDL
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What are the products of translation of apoB gene mRNA?
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Answer: apoB-100 and apoB48
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True/False: Omega 3 fatty acid increase ABCA1 and thus increase HDL level.
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Answer: True, Omega 3 is in fish oil and tea
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What are the main function of chylomicrons?
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Answer: transport dieatary TG and cholesterol
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_______ is required for chylomicron recognition.
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Answer: apoC-II is an absolute cofactor for interactions of chylomicrons and LPL. Absence of apoC-II prevents the hydrolysis of TG in chylomicrons and results in severe hyperTG and pancreatitis.
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True/False: chylomicron levels can only be controlled through diet.
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Answer: True; except in the case of type I diabetes where pt use insulin.
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Absence of functional apoE results in what?
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Answer: results in type III hyperlipidemia (high levels of chylomicron remnants in the serum). This is because apoE is necessary for remnants recognition.
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What is the function of LPL?
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Answer: LPL is a lipoprotein lipase. I is TG hydrolase. It hydrolyze TG and produce free fatty acids which are uptake by adjacent tissue. It requires apoC-II as an absolute cofactor.
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Imagine what would happen if there is an absence of HL and apoE.
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Picture: apoE mediates remnant uptake by interacting with hepatic lDL receptor and the LDL receptor-related protein (LRP). Absence of HL or apoE will results in impedement of remnant clearance by the LDL receptor and the LRP, increase TG and cholesterol-rich remants in lipoproteins in plasma.
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What the hell is LRP?
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LRP is LDL receptor-related protein. 1, the remnants are sequestered by the interaction of apoE with heparan sulfate proteoglycans on the surface of hepatocytes and are processed by HL to further reducing the remnant TG content. 2, apoE mediates remnant uptake by LDL recetpro or LRP. LRP is important b/c it is the back-up receptor responsible for the uptake of apoE-enriched remnants of chylomicrons and VLDL.
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Explain the formation of HDL precursor.
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Answer: initial hydrolysis of chylomicron TG by LPL, apoA-I and phospholipids are shed from the surface of chylomicrons.
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T/F: chylomicrons are precursor of LDL.
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Answer: False, chylomicrons are not precursor of LDL, but the dietary cholesterol delivered to the liver by remnants increases plasma LDL levels by reducing LDL receptor-medieated cabolism of LDL by the liver. Therefore increase LDL level.
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What is the function of VLDL?
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Answer: VLDL transport endogenous triacylglycerols from the liver to the peripheral tissues.
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What are the protein components of VLDL?
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Answer: apoE and C-II, (and apoB100)
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T/F: catabolism of VLDL is similarly to chylomicrons because it is done by LPL
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Answer: yep, it's true. LPL hydrolyzed TG from VLDL and now have IDL then further to LDL.
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TG + CE to form VLDL by what protein?
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Answer: MTP in the ER.
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What is the function of LDL?
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Answer: endogenous cholesterol to peripheral tissue
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What is the T1/2 of LDL?
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Answer: high T1/2, about 1.5 to 2 days
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What is the protein component of LDL?
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Answer: apoB protein
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What is the function of apoB? and What happen if you have a mutation in the C-terminus of apoB?
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Answer: apoB binds to LDL receptor. Absence of apoB protein will lead to hypercholesterolemia. --> hypobetalipoproteinemia (low LDL) and leads to fatty liver.
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What are the source of LDL?
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Answer: IDL by LCAT and HDL by CETP. CETP inhibitor can be a good drug b/c it will increase HDL and lower LDL. HDL can also be converted to IDL by CETP
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So what is the most effective way to modulate plasma LDL-C levels?
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Answer: manipulations of hepatic LDL receptor expression
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T/F: thyroxine and estrogen enhance LDL receptors gene expression.
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Answer: very true.
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Back to the question: what is the most effective way to alter LDL-C level?
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Answer: decrease saturated fat and cholesterol consumption. Pharmacologically: drugs that act by enhancing hepatic LDL receptor expression (statins)
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So why is LDL become atherogenic?
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Answer: when LDL oxidized, a required step for LDL uptake by the scavenger receptors of macrophages that leads to foam-cell formation in arterial lesions.
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What is the purpose of HDL?
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Answer: remove cholesterol from extrahepatic tissue
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What is the function of the ABC-1 protein?
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Answer: cholesterol is transferred to HDL by the ABC-1 protein
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What is the result of ABC-1 mutations?
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Answer: leads to cholesterol accumulation in liver, spleen, tonsils, and neurons (Tangier disease)
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What is the major apoprotein in HDL?
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Answer: apoA-I; a marker for CHD: high apoA-I, less likely to have CHD.
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2 reasons how HDL are protective against CHD.
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Answer: 1. They transport cholesterol away from the plasma and peripheral tissues and 2. they inhibit oxidative modification of LDL.
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What is the MOA of fibrates?
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Answer: increase apoA-I synthesis
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ABCA1 deficiency will decrease or increase HDL?
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Answer: decrease. ABCA1 is a presence in macrophage and it is responsible to transport cholesterol phospholipids to prebetaHDL to form HDL3.
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acetyl CoA --> HMG-CoA, what is the next step in this cholesterol biosynthesis?
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Answer: HMG-CoA converts to Mevalonic acid by HMG-CoA reductase
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Mevalonic Acid --> Isopentenyl diphosphate ---> farnesyl diphosphate; what is the next step in the cholesterol biosynthesis?
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Answer: farnesyl diphosphate to squalene by squalene synthase.
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Lanosterol ---> cholesterol requires how many step?
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Answer: 20
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What 2 main components cholesterol degrade into?
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Answer: bile and steroids.
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Describe basic mechanism where each drug class act to control hyperlipidemia: ezetimibe, statins, bile acid sequestrants, fibrates and niacin
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Answer: Niacins and fibrates increase HDL level by inhibit the degradation process. Statins act as HMG CoA reductase inhibitor in the cholesterol biosynthesis. Bile acid sequestrants decrease the re-absorption of bile back to the system. Ezetimibe, look it up
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Tell me about bile acid sequestrants as a drug class to control hyperlipidemia.
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Answer: it is an anion exchange resins; it removes glycocholic acid and taurocholic acid, and cause increased uptake of cholesterol through LDL receptor, it is a choice treatment for children; eaten as resin; except can prevent absorption of drugs and vitamins.
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T/F: Statins mimick the intermediate state of cholesterol.
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Answer: True; it inhibit the endogenous synthesis of cholesterol. Increase LDL receptor expression.
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What are significant of SAR of statins?
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Answer: 3,5 diol, with bulky group sterochemistry is important. 2 carbons between 5-OH and ring.
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T/F: statins can reduce VLDL precursors.
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Answer: True
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What are significant of the pharmacokinetics of statins?
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Answer: lag phase for several weeks, 25-60% decrease in serum cholesterol
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What two other drug classes can statins combo with?
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Answer: niacin or sequestrants.
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What are statins adverse effects?
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Answer: hepatotoxicity, myopathy, constipation (legs and arms especially, general fatigue)
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Tell me the mechanisms of fibrates.
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Answer: mechanisms not understood; appear to activate PPARs complex. Activate lipoprotein lipase, so they affect lipoprotein catabolism.
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What are the therapeutic effects of fibrates?
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Answer: decrease TG levels more than cholesterol, decrease VLDL levels, moderate increase in HDL levels, variable effects on HDL.
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Fibrates are commonly used in what type of hyperlipidemias?
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Answer: type III, IV, and V And often used in combo with bile acids sequestering agents.
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[aromatic ring]-o-[spacer group]-CH2-COOH is a structure of what class of drug?
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Answer: fibrates
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T/F: fibrates are esters and prodrugs that are analogs of phenoxyisobutyric acid.
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Answer: True
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Imagine the fibrates MOA chart.
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Fibrate-->PPAR(alpha) --> activated PpAR (alpha)/RXR --> PPRE/target genes --> 1. increase reverse cholesterol transport 2. decrease TG 3. decrease inflammation 4. increase HDL synthesis 5. increase LDL particle size.
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Niacin increases or decreases the production of VLDL cholesterol at 0.5 to 6 grams daily?
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Answer: decreases
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T/F: Niacin reduces TG and TC
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Answer: True
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T/F: Niacin is mostly used in Type I hyperlipidemias
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Answer: False, use in type IIa, IIb, III, IV, and V hyperlipidemias.
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What are some side effects of Niacin?
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Answer: dyspepsia, flushing of skin, hepatotoxicity.
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SAR: what functional group is required for a functional ezetimibe?
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Answer: N1-aryl group;
other SAR: 4(S)-alkoxyaryl group; 3-arylalky group |
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What is the function of F and 3-alkyl-OH in ezetimibe?
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Answer: F blocks untoward metabolism and 3-alkyl-OH mimics activating metabolism
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What is the indication for ezetimibe?
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Answer: inhibits absorption of cholesterol from the intestine. Treatment for type IIa, IIb, III, IV and V hyperlipidemias.
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T/F: Ezetimibe inhibits NPC1L1 in the enterocytes from transporting cholesterol and plant sterols.
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Answer: T
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What is the purpose of diuretic drugs?
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Answer: designed to alter the balance of water and inorganic molecules in the body; regulate the level of body fluid.
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T/F: Kidney is important for all inorganic substances.
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Answer: False, zn and fe are controlled by the absorption of GI and excretion in the bile.
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What the heck is ADH?
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Answer: ADH (antidiuretic hormone) that increase water reabsorption at the collecting duct system.
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Filtration rate is determined by ______ pressure in the glomerular capillaries and bowman's space, the ______ pressures in the glomerular capillaries and bowman's space.
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Answer: hydrostatic pressure, colloid osmotic pressure. FYI: filtration under pressure is aka ultrafiltration.
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What is the rate of ultrafiltration?
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Answer: ~120 ml/min, rate urine formation is 1 ml/min
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The descending thin limb is highly permeable to ____, whereas its permeability to ____ and _____ is low.
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Answer: water, NaCl, urea
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The ascending thin limb is permeable to NaCl and urea but impermeable to ______.
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Answer: water
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The thick ascending limb actively reabsorbs _____, but is impermeable to water and ______.
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Answer: NaCl, urea.
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Thick ascending limb goes b/n afferent and efferent arterioles. The area that is able to sense the concentration of NaCl in the urine is called _______.
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Answer: macula densa
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If the NaCl concentration is too high, it sends a signal to afferent arteriole to _____.
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Answer: constrict
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