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pharma fouda 2_p108-109.pdf

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CleanlyBoston

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hyperlipidemia lipoproteins drug effects pharmacology

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Part 1 1: Hyp perlipide emia an nd drugs s that lo ower pla asma lip...

Part 1 1: Hyp perlipide emia an nd drugs s that lo ower pla asma lip pids █ Bas sic inform mation  Lipooproteins consist off a hydroph hobic lipid d core (TGs s or cholessterol) surrounded by a hydrophilic coat of phospho olipids and d proteins (apoprotei ns), whichh render themm miscible e in aqueouus plasma.  Theere are 5 classes c of lipoproteinns depend ding on the eir relative proportionn of the coree lipids, type of apop protein, sizze, and den nsity:  The e intestine e is the maain source of lipid pre ecursors. The T liver i s the mainn site of syntthesis of liipoproteins s. The adi pose tissuue is the main m site o of storage of TGs. Fat cells don’tt synthesizze any lipo oproteins. ▌Lipop protein metabolis m sm In tthe exoge enous pathway, abssorbed cholesterol and a TGs aare transpoorted in plassma as chylomicro c ons. On the vascu ular endothelium, tthe core TGs is hyddrolyzed byy a surface e-bound lippoprotein lipase l into FFA whicch enter thee tissue andd utilized. The T chylom microns reemnants (c containing mainly chholesterol) pass to the liver wherre cholesterol is sto ored, oxidized to bilee acids, o or secretedd in the bile e. Alternativvely, it may y enter the e synthesiss of VLDL. In the endo ogenous pathway, p cholesterool and ne ewly synthhesized TGs T are assembled ass VLDL and delivered d to the blood wheree TGs coree is hydrolyyzed by 203 lipo oprotein lippase into FFA as d described above. The T smalleer VLDL particles p havving less TGs T and more m choleesterol are now termmed LDL. C Cholestero ol in the LDLL may be: (1) utilized by the tis sues; (2) re eturns agaain to the liiver; (3) de eposited subbintimal in blood b vess sels and ca ause atherrosclerosiis. Whe en cells diie, cholesterol in the eir plasma membrane es is returnned to the liver as plassma HDL particles. p HDL H functi ons as scaavenger lip poproteins.. ▌Class sification n of hyperlipidemiia Prim mary (fam milial; hered ditary) hyp mia: is genetically dettermined. perlipidem Class s In ncreased lipoprotein n Synonym S Type I ↑ chylomicro ons Familial chy ylomicroneemia Type IIa ↑ LDL Familial hyp percholesteerolemia IIb ↑ LDL and VLDL V Familial com mbined hyp perlipidem mia Type III ↑ IDL Familial dys sbetalipoprroteinemiaa Type IV ↑ VLDL Familial hyp pertriglycerridemia Type V ↑ VLDL and chylomicrrons Familial mix xed hyperliipedemia Sec condary (a acquired) hyperlipid demia: – Hyperchollesterolemia: hypothyyroidism, nephrotic n syndrome, s , and drugs s. – Hypertriglyyceridemia a: DM, alco ohol, gout,, chronic re enal failuree. 204

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