Pee og a -.5,yea:old man wit ype 2 ates mattis comes othe eneigentydepartert th ever, ase, owe inl sacar, an ‘ankpan. The patent nasi of aabetc autnomc neuropathy wih Blader dsuncon and nes been hspzed mule nes or recurent uray ractinfchons. Hs tamper s 3-4 (18) bled pressure ic 9450 mmHg, ad use T8mn. Heght = 160m (5 ‘in weit 150531 and Bilis 48 kg On extn, eres suTapUDE andl Costoverebral angle tenses, Aer even fcr ard erat tests om ha prt horplzatn, te patents an empire ance regen ha ces av ane ode ‘ie cteanng te appropiate dosage, netesplal tarry ses an ased Dog weQH tha saver han he pater acta dy we ‘Which fthe flowing best exes th use fis adhsted pare? (OA Oita te gs neath acer id cmpariret| '. Eimnaton tte dug pedemnatyby hapa clerance © © Metantsn ore ug cme vis ee tines © 0. treanug emoes argh egies of plasma prt tang . The cigs thy sequetred wn pose tissues ial Copeer doe a ee -.5,yea:old man wit ype 2 ates mattis comes othe eneigentydepartert th ever, ase, owe inl sacar, an ‘ankpan. The patent nasi of aabetc autnomc neuropathy wih Blader dsuncon and nes been hspzed mule nes or recurent uray ractinfchons. Hs tamper s 3-4 (18) bled pressure ic 9450 mmHg, ad use T8mn. Heght = 160m (5 ‘in weit 150531 and Bilis 48 kg On extn, eres suTapUDE andl Costoverebral angle tenses, Aer even fcr ard erat tests om ha prt horplzatn, te patents an empire ance regen ha ces av ane ode ‘ie cteanng te appropiate dosage, netesplal tarry ses an ased Dog weQH tha saver han he pater acta dy we ‘Which fthe flowing best exes th use fis adhsted pare? VA Dante the rg eso the racer Fue camparimen (268) 1. eampatenctbe aug pedemnaty by pate clearance (6%) . etaats of me rg rence va ern ote hn 1. Tecnu exnbts agh dees of pnp beng 21%) The cigs thy sequestered wn pose issues (24%) mie ea sass eseane0 lenaton Obesity effects on loan and adipose mass Co GB ial~ 7 Obesity effects on lean and adipose mass ‘Adipose z i : z a | Zs ‘ug re ypealy dose to mantan plasma cu concertos wanna eye ange. Athaugh hed dug desig convener fr odes napa, sng based on body wight (23. rg) ten used 0 mgrove STAY ardeficacy, aria f medestons wana nao therpauic window (9 hepans,srinephcoses, nechcs) Earen ‘rugs re ypcaly dosed to manta asa du concertos within tage ange. Attough ned dua dosing convenient fx overs anaes, dosha based on body wlght (og. maka) fen used 0 merove slaty anficacy, parca for medetons wih rarow therapeutic window fg heparin, ainoghccsies, neshess) ‘ey wt tet ona acta clsrance ana vse of erturon. Onin race ate colte dae wean bea wert (ete weit al noradpose sss, ncudng sce, ve, dneys). Lewis the lune of tovion forrest us se gs De 25 lean So mos ereszes Hover obesity causes a proportional inereaaeinatpose maas vhchcan hive vale loc onthe ‘etune a dsbvon copending ante sou of aug 9, ero, Pyaonnoe} Aminogleonies as lnge charges molecules fat cane cross cel membranes fer vekime otis med the ex accii space, ich neste cny mrgnalyncbese nics. As es, dsing in ebtee patients: baton an adjusted body might tat ike rt ‘econ ny apart 40%) oe excess apes mass. (GhoieeB) The et of mination doesnot dresymoac weigh baced dug desna, ase ome fa that phic hus more on ndgoneptic elminaten Fumes amigos ae nt eltne ye erty ae Heel by the orl and excreted uchangedinte une (ehoie The vast marty of rue nucng amnegycates undergofect pct zu aneretablam In ator, bey ict ‘aust wen gard mescaton dosing afe usualy made acorrg oe way 2 Artes win te Das sues (hoieeD) Aci cogs wth a ih oars of loa pret inna (ea warfarin) are retaedin he nraasclar pace ad ave it ‘elie of scl tats as acted by Dey weg. In cet, amnoyosdes have mn plana pcan Brg and can se ‘cereal oe instal compartment. (Ghote B) Lier drugs pron ener ito adpose sues the volume of itbuon is beter cola wih tl bod weight an wr anor aust body wah. Hg peti rug (6, penn) are tight sequestered itn apse tse and oten que an rit loot ode osu toes and ateve adequate etm evs Educators objective: Mary aus are dosed hase on tbody woah to mprove Sattar eicacy ncbese india. use ofan bay weg an aust boo weighty be necessary when des hyontc hugs (eg aminaycoie) fat oat eit to ado taeeek dent si ee Awinogieosides oe lage carga molecules at cane criss cel meneranes he vlume of tans nid oe extacear space, ihntessseny marpnalym chess nahn. As 3 eeu, dosing ebetepaterts is based cn an aunts body weight iat ister account ony aperin (-40) ofthe excess aes ass (heiee B) Th ote of elminaton oes not dec mpact weigh based dug dosing asd lm he at tha poh dug more en ‘dogo hepatic einen. Futhernoe aninogyrosies ae nt metoizs byte ver: thoy ae Foe Fredy the lars nd ‘rset unchanged inte wine (oie €) The vast gory of rugs ndudngannelyoae, undergo fret net 2a) ander etablem. natn, body wight _ucenons wih regard to mediation dosing are usualy mae accring oe way actu dete wth the ba sues, (rote D) ile cs wn a igh degree of plasma pen tingng eg, waa) ae elaedin ne nrevasea pace ad ave tnt ‘ele of drut tats ss aos ty Sey weg. Icons, arnogcoses have minima plasm pon nrg and can ste ‘exer ote inert compartment. (oie ) Lorie dre parton ener ieadcose tases the volume cf itbuton belt cole wih tl boo weight an wane adustes boty woh. Hoh pei duns (en, Shere) are ay sequestered thn apse issue and ote equ an rit leona dove o saute at tors are acteve ade serum eas Edueatona objective: ary duns re dosed based on otal bed wet 0 merove safety and eficacy.ncbese indi use ofan by weight an acted ‘body weahtmay be necessary when desing heopti has fea amnesic) hat do et dette ito adpose tse Reternens Pamacsbay General Principles une of stn ial CoSon > ao a Oo {A -yaols Cavesan lt savers palneph somata he hosp He pas sel stays isan orate hypertension ance epsoces of ansert ischemic tacks. Hssseum reatnine ees 32 mg: there, he needs be sare onan artic hatcepende aly ovnen‘eral lence, Wheto the foun characte she arin les ave # haat etal Low yoke of dsuton Poot ol abeeson ch potty Poa: panetaton io me CNS o! ialcomecie B PM a ee {A -yaols Cavesan lt savers palneph somata he hosp He pas sel stays isan orate hypertension ance epsoces of ansert ischemic tacks. Hssseum reatnine ees 32 mg: there, he needs be sare onan artic hatcepende aly ovnen‘eral lence, Wheto the foun characte she arin les ave # haat etal A. Low elune of stn (17%) 8B. Poor orl absoton (8%) 7 High pty (675) Lowa eden (12%) oat peetaton ino me CNS (4%) pletion ‘otartomatin and atabolsm bt some drugs are aso pred elminatdy he vt noe lean fees. Drugs wi igh mrs heptc cearance endo have hah eee and aig olan of etovion. Highly loch rs no be poor einai he kney as these agers rapycoss ber cel membvanes fe atone he sie. sgn oe (pd sui) alors ne rug ta cose Clabes mate ast ai ert hepeaes_can hen be excited ei Bok a aman e832 Ponaie et uber hero “The fey isthe rina st of exon of most rugs, wih witout rr chemicalmesifcato in heer. Thee the mars of tua ‘otartomatin and metabolsm bt sme args are ao predinteelminstdby be eto he lean Tees. Drugs wah igh mn hepa cearance endo nave nn peek and atigh olan ct stove. Highly Inn crs tnd oe poary eran e ney asthese agers rapid eoss bec membranes afer tratono eet he ssi sano psy) alone ecru ta cross clla Daas mace ast ert hepeaeyls. can an be encod ei or twough chermateds of dimain. In addon gh pd soubilyassues a wide dstbwin 2 many dent sues incu he bran Wet andapse nese, (note A) orgs wi alow stibutenvlune tobe conte othe Hocdteam aed ot ase aay rough Repu eo theble, Ths, 3 ug wih alow Vwi te ih lass poeh-teundand yoni aking ites vate for hepatic mabe ard more ‘aad vali excretion unetge inthe une (hoiee 8) A crup thats not wel absorbed ray may have aighpe-sseme teas eimraton be oat pdscible nba cases it eer eet (Ghote D) low rat ofresbuton fone compare earth imples wi seb or sient indeshiicty. These aster toremain inthe ireaiascuacomparinent and be ciriraesb he ees (Chole &) Por cent nove system penetston dats hats rg ish tapi, andere has alow var ofcetovton. Is three outa that he sare du lb iit nage amour he Net Edueatons Obectve Wier ney the prvay ste of elmnaion of most rus, the ers the man sto ofbevariomaton ches gers roparton fr eimaaten Drugs nat remote oan (hgh Ve goa peneaten ina CNS) ae reerentaly processed by he Were mat pola ‘camgunds for easier elminaton ne le andurne. Ler eas (2.9, cious) fhe concomtart us fer hug may imi or enhance the clesrance of rugs metablzd in eer Pramscobay General Prncipes Drug suche and preperios GB ialhepatic as these agen rapycoss ber cel mambanes afer atone he sie. an sooty psu) tows ne ug ta rose cllarDaers mace ast i ert hepeaeys. can hen be exited ei or trougetermateds of simnsen_ addon, high pd souby sess se dstouton o many Sfeenttsues inducing the bran We, ansadose ss (oie A) Orgs wh alow cetibutonvlune tendo be confined othe Hocdean anand ot ous ready trou hepato (heb. Thus, ugh alow Vie igh laa poten Sound ype making lees wale fo hepa abo ar me ‘dy aval fenton unchanged the une (Ghote B) A cup thatis not wel absorbed ray may have atigh essen sta emiraton be oat cll. nba cases it ie urvalale oe War rhea clearance (Ghote D) Alou ate freien fone conparnert anther imps wid seb or sient incest. These ster foreman inthe remiaear conpariman! and be chara the edhe (hoieeB) Por cen nevois ssa seneaton cates hat 2a sik rt psi ard herrea ow vue of stouton. istherere aso uniey that he sare du lb ited lage amour he er Edveationa Objectve: Wien ines the privy ste of emraion of mes rs the vers thea ste ofbetansiomatin of hese agers reprtinfr felmaaten Dns tat remove ogni (hgh Vs goad pneraton ina CNS) ae preteen processed by he Wer emake oak ‘campeundsfor easier eminsion nee andurne, Ler sess (9, cross) rte concemtartus f ter gs may itor enhance the clearance of ergs metabotzed in he er Phamacsibay General Prncbes Drug suchreandreperies ialCu ee - wa aes ee OR esearctars a develop 2 neu ycopepte ane inarto arcane. Suscptbytsig reveals hate nen aus tate gas ran-postve gan t setum concentrations above 15 in. Two eetet dosage resmens ate devsopd io acre a get serum teughcononaten of 1520 ypml:one aeminsted 61 gam eon Rows ad he eter 62 grams every T2heus. The two repens a tetedin heathy veliees urn an eah-ohase cra tal. an he flowngpramaconete pots are cbianed Zornes a l, i yop incetaton Tie fs) a oa] Cn Os) ‘Compared the 12-hour osng regimen he hour regmen mest ikl exit when of the ellwing fours? © & rare arse tase ages O 6 moet patent conpance OO. Lane do et OE Naronr trae wns — oa] - wa ‘Compared the 12-hour osng regimen the hour regmen mest ikl exit when of the felling fours? ‘A. Cece renal eran (4) 1. agner overage pls chug eves (12%) ©. proves patent complance (2%) VD. Lower dp oat (6%) . Narower therapeu wndow (105) gies ox usec oseane0 — LW rescore Toco es E a ocmaeniesree 8 Mk ‘ong doengregmene ate pcaly designed to maurice echvaess and mnie ty, The above graphs cmparng octet ‘ragrens wth he same ea dose &pras!2n) bwin ere esingizvas fe, 6-72). Bot regimens hve sila wough om eves, lower concentaton vel lee nx dose ard maria plasma levels above te bara cot (a, 5.20 yah). As such, both = rapier af kat exit similar eae. However peak and average drug levels ubanlygher wth 12-hour dosing 28 regimen. Because rg teciy mest en cores wth pak or average las dug eres re hour regimen ikl thave lower onety {crle A) Cease ere ta bn dora on he ic eames fe ape. ced ashe amt ters Co ialar) GB aren ‘ong doeng regen ate pealy designed to manic i echvaess and mnie ty, The abe graphs cmparng octet ‘ragrens wth he same ea dose 6 pras:2¢ np bu win ere sing eta fe, 672). Bot regimens hve simlar wough eves, lower concertaton vel ler dose ard maria plasma levels above the bared cof (a, 5.20 yah). As such, both pens af kat exit similar eae. However peak and average drug levels ar ubsanlygher wth 12-hour dosing regimen. Becayse rg txciy mest ten cores wth peak or aterape ls dug eres re hour regen sil thave lower ety (note A) Ckararce (hepatic orn ofa sbsarc depends onthe ric pepartescfthe agent It defined asthe amount of asm thats eae of he dun oer ave ers (eg. nin). Drug carace pica te same regaess ofthe dos shale (hole B) Average plsa dg levee reer when fed amount trai gen nar ide doses. In tis xampl 4 grams ao aomnisered every 24 hous, eterin2oses (2 regi) or doses (regimen). Theor, hermrefeauet car egmen wus resulta eravernge asa dg lees (note ¢) Fant compiancssineoased won the fequeny of ose minmized. Cy 2 doses per dy ar needed wih fe 2hour regime, honerer the hur egnenneeds 4 doses ais helo be more dsupive fhe patent's sche (hole &) The erapauicwndou retro he range of rug dosages ht hae mn appropate iia fect it bogns atthe wes dose at hich te cugis efecine ans ends ate gest dose witout sgncat onc eects, Drugs wih raw therapewsc wow are oten dosed more feet to revert re sinsin pasa corcentaon. Edueatona objective: ‘rua dosng regres wth mere eaent eng have lover eakard average rales whch can ep redice ug oy Pamacsioay General Prncibes_Serumupleves and hate ial Co= - wa ey ‘A group times stung the ramacoenatc proper of he anashearug papatl A alate tomato tthe feparedanda sige tess aaa ad qunea pgs. Blondand issue samples we hen coleled at edema ne teh \Conerratons of raioacive origin he sapere assessed by iqud scion couning. Te raph blow ements ne cr cxncenratoname reaionship mn varousbssues.“The redne ene graph mosey coraspondsto which of re folowing sue? eo GB. e Car Le Ce “The redne ene graph mosey coraspondsto which of re folowing sue? A reat) ney 10%) es 2) ung 5) ‘Stata moscie 4) onites LW rescore Toca es E eocestonicms Mk ‘Administration Peory- vascularized Petpheral ‘compariment Plasma = iia apis a Wesvascuarzes *stveta miscle ra Bone a corommen. 2200 ra 2 me Kidney ta Liver = Lunge Heart ovtians ‘up astute roms the teat hh erage are deere og! issues dependent a several ads, Su steel Hood ow anddlug crvactenstes. The parmacounetc pote ct top atesinet rs Such es opt, canbe pede usr a mule Compartment mote ot ambition Folotng ominsanan 09 ange ravenove Sei arg leele ehh ine earl empartmant 2, asa) However te cups qh dstbvld a he wel-prtused peripheral comparment (a. an We. eeys gs) eo he err ran — ear) GB ours ‘rua distin src unl the rte at hich drugs are delnered oat sues dependent on several fais si 3s reena ood ow andua characterises. Th ptamacckinesc pier fophc reset rugs, sich as pop, canbe pected ura 2 mult- {omparment nots o ssvinion Foloing aamassen ofa sre ravenous So ees aehigh o canaleempsrmane (2 ssna} However edup's qc stbtao he wel perused peripheral compare (2 ain. We aeys gs) eta ne Increased ipepicy of he tsues compared whe od ‘ove ue, rg reiswbutn at acu thous he cena compares ito he pooped pespharal compart, Sc ‘mutl fat bone wich has he het vm of drt fr pop apes. Reistbuton acre api wih Inophic dugs and Isrecpnste rth shat raion faction seen wth conmony sed anesthetics sch 35 propeto (roiees A 8.6, andb) Tese organs nave nh ood Naar ate cansdeted pr tthe wel paisa pergheacanparnent “hoy wap tate up rugs rome central comganment ad are vsalzed 2 the dashed neon he above graph Edueatons objective: Flour nravenus admnstaton, 2 ney opi erug wl be ply dstbvedts gens wth hgh Hoed Now ep tae, Wer Kanes urge). The cg shen edsrinseao sues wih rete lowered fow esata mus, f, bene). Th acouns fore short uation of acon may crime wsed anes, such 2s opt Pamacsoay General Prncpes Anessa Ca ialS eO) a aren ‘an 2,yaold woman wou ote oe ran patent evan. Sh reer moves wh Mer dari. Te potent egos ent cazaness bu cmt povde atonal deals regaringhesyplons. Medes Sty clues moderate deers hypeenson Wanset Inenams aac depreeson, ona cerns. Boas petri 12072 mn Hg and ule San anarepe Merle examnaton ‘Sows dsoertaton ne and pace stroma deep eon refines rd nofocl sensory or tor deficits. The pers mediation sche o! ial) aren ‘an 2,yaold woman wou ote oe ran patent evan. Sh reer moves wh Mer dari. Te potent egos ent cazaness bu cmt povde atonal deals regaringhesyplons. Medes Sty clues moderate deers hypeenson Wanset Inenams aac depreeson, ona cerns. Boas petri 12072 mn Hg and ule San anarepe Merle examnaton ‘Sows dsoertaton ne and pace stroma deep eon refines rd nofocl sensory or tor deficits. The pers mediation sche A. Amicopre (%) 5. Aspirin) © Operon (8) ‘onepeat 5) pcrioaniande 2) F sewane on) (Common medications to avoid in older adults (Beers criteria) o! ialcmacnicrer 8 Mk (Common medications to aveld in older adults (Beers erteria) Antchotinergie 7 Fist gereatn asians 1 castontestinal anspaenodcs cardiovseuae + Aha loters (as anitypenensver) + Cenalyactngalphe2 anos + Many antares rt + Aoipsyetaes + Barta, benzodarepnes& oe hypcti Endocine + Lerg-acingsufoniess + Sidngscle isin Pan Nonscectie NSADs meitrpretd 253 new nicl coin SADE nrc nt ry de ar) GB ee ee eee comers, dug rug iteractons, an poor ru complance. Petypharmacy e, 5 resco ander veh outer medcaos) so pavealr concen te ley and can lead oa prescrbng cascade, n which adtonal drugs ave gen for adverse fects hate ‘The Beers entra wer cove cee age equing cautcn in era patents, Frst-generaten antisamines 5 Lipnennysrarins) anche cre wth anni acy can ncese te nee oconkionhauenatons, anes oy, an Censor are shoul be aviedin is pxpulion. ther conmony used edctons hat shoud be avoiedin he ley ee ‘ecoazepnes (an er secatng madcans),artpyehoter many aviary (eg Saber) nd cenaly acing kel macearen NAD reel Ty Se - = ‘toe paters ae at creased ik for adverse of means de to decreased hg destane, cognitve and senso deft, use comerbetes, du cugitractors, ae poor rug compliance. Plphamaey (e, 3 prescition ander over-he boo mass eaing lowe plasma coneeneatins we he rugs admins the sare weghased dosage as geno ad pate Furarmare, neonates hove ar iatitebod rane tat ereazesthesereabt of mary susdarces othe CNS compare. mien (non to nereasig easton volute can ease the sk of CNS a), (hole A) The neris not fy develope neonates and as deceased expression of rp meatelcna ereynes en, etochae PEED ‘eoenyes,guzworidatonerzynas) Tecan odo deceased caarae of get ae hpatieay naaboloes ep acearnaphe,Ini exare, a nove aconestce artis anstered eat and neonatal paterts sng the same waghbased dosing regimen co ‘Smghg) However, asm cncesios of te gas ower acnates canted ae adit, eng deresea efieciveness Necates have svbstartalchamacchintcierences compared adit patents that fect rg absrpen, Sittin, and eraton CChangsin guironiesinal aramcesnntoraes eg, deceased gus pS reduced resial mi) an have arable flo the arse ct aly aomnstered us. However nhs case, te rugis Bang admnsereainravanously, so charges nabsopion ae riko be the cause fe plasma concertaton deepaey Neonates ssa hve an ncreated pcp ttl body water ih slover canter fa fat crpaedte aus The ference nosy congoston resus n waesouble rugs 9 aring)cosdes, vanconyon au lage than expecta volume of estbuon 1250212 boy mass esing to lowe plasma eaneenatins when he digs admnsted athe same woot-ased dosage as given oad paterts Furthermore, neostos have an imate Dood ran bare hat creases the pemeabity f mary susances ino the CNS conparirent, ich nation to incressing the dibuon volute) can inease the ik of CNS toc, (hole A) The erie not fy developed neonses and as decreases expression of rp metabkar eraynes ep, ctchome PASO 'seenames guewonidaton enzymes). Thiscanlead to deceased ceararce of rps tha are heptcaly meatles eg, ceamnoghe, ree eet aetna (notes 8) Rel los ow and rear fitton ae ae decreaedin neonates compared 0 as. Fer cigs that renal ceed ‘ced real eararce would cause creased scum dug concertos, eter leading to towicty. Howeve nhs ste eum (holes ¢) Neorates hae decreased (ot icrease) asa prtin concentatons compare io aus, wich can cease ts evel fi ‘ojnbnund duns (en, phon, percin). Elevate iin lores in eanates can futerincrease the carcenrtion of urbe a by ‘asa hem tom abumie tary sts, Education objective: Necstes ave ahha propaton of Sed ule compared de Thi can esa ever plasma concentra faerie eg # hey are aomnsteed ane sane wes sed dosage a5 ent atl persar) GB ‘Changasingasritesial araetersin neonates eg, deceased gos pH reouced resi mci can hav vari econ the absorption of aly admnseredcrugs. However nhs case, te drgis beng aomnsieedinravenousy,s charges inabseton re robe the enue fhe plas concerto Sarena) Neonates aso ve an nerease pcp foal boay water wih slower carter obo fat compaece ahs The ference ny conoston ress n wate soluble rugs cg arinoahcosdes,vaconycr) having larger than expected volume of estribton rave t2 ay mass ean tl plsia eanceneatons when a gs admis th same wag ase sage 25 gen alt ates Furtarmete, antes have an iste Dood tran barter hat ecieases the pemeatty of mary sbstances he CNS emt. ich ain t increasing the dtrbuon volun) ean nase he ik of CNS tn, (reiee A) The ners nt tty develope neoraes and has decreases expression of up mately eraynas ey, cco PASO ‘aoenyes,glzwtoidaton ery). Tica odo deceased cenace of gs hat ae hepatcay stabloes eg, acearnaphe, mone). However, ths would eeu mincreased (at cess) plasma cup ove, (note 8) Renal los ow and gamer Maton ae ae cecreaadin reo compared to AE. Fede at realy ec ‘redied renal Ceaance woud case ereased eeu dug concertos, potty leading tnt. However nthe uy the eum ‘encenton flower neon han ns (rete) Neorates have deceased (pat isease) plasma pcten concenatons compared oats, which can seas Ne ves ighy priennund dice (6, phnjan, pancin). Elves btn nels neonates can fnerncreae te corcanrton of ureeuns o >) ‘estan hen om abumin ra ses. Education cbective: Necats have ahghe proparion of Sey ater compared sau. This can esutin lower pasma concenttons cf water saul gs f thet are acminseed atthe save wei-ased dosage 2 given abu patents Phamacsoay GerealPrncipes Aang Co iala RC) Cr) Cn Os) 4 ‘A woup tives cae conscing 3 phase inca lf ney developed syne cpl tha ieee rages cpsty 5 emorgne.Ateralngetonct a aed cose by sever Orie, ne plasma concetatonct he dg Messed an GeerMnEs Be & funterpeune. Rectal arinaraion of nese oo he erows a psma carcenaten wal were Pepe rnge, amc a nine re leei easiest arte. Yenf e kong bes acpi ne cbse eetenesn up eencenabe low ea = OA Decreased dun den oh her a OB. Gener beos own esrevenothe resin ea OG EEE EXE ©). taper vcctor are Ca ialCu Ce aren ‘A group times suey conduct a pase cncal oa ney dewteped syne apal hatha wie te aralgese capantty fetmapne. Ate eal ngestonat 2 aed cose by Several obese plasma canceriatonef he dug measured ae deraned be ‘herape. Rectal asmineraon ofthe sare dose o he drug shows plasma concenaten wel thn fe therapeutic arg, amos Goibe Pe level measured ater oa take Wh fe feoningbestacounsfor he eserves ference in dug concenaten lng recta YA. Deceased rg dover he er 7%) reste bes ow sagen fe ese (4) A 8 ©. creases atscrpton ate of eda (18%) 1. Larger coe sce area) eked rent ond ow (0%) Anorectal venous drainage Super rectal vein (to poral stom) rer vein to caval system). a eo‘Anorectal venous drainage Super recta vein (to poral ~] tocaval year) Blcaraabity ste acon fn adrinistes drug at eaches he ster cicaton charge, Or Beavalaiy is depends onthe Inna tear properee he fg eel Fay fest pate mtaboiam athe dug undergoes ensynee preset meine a er cru ates Ng esse Meals Ae down exensie ad wi Pave alu cancenv ate the Ste AUN (oearen ‘Bloavalbity te raton tn arin drug at eats ester cation netarged, Ca caval i depend onthe ext absrpve properties oe gas wel 35 ay fest pass metabo a he dug unelgoes by erzynes preset n Resin a Iver Aor at its high esse metabolem is troken down extensively nd il Fave alow cncenraton inte estan eatin (ew ‘eavtabiy). To eficeny ne cuns high fstass meats, thr rte of minseaton ae enpioye en, vero bing eco bypass the pet rulston Rectal rg ainsatensuppostory)alons paral pas of rsteasseaboem. Venous hinge ote anerecum above the dna res ohe poral venous sytem vi he super et veins (ino inferir reserve). Howes, th resin blow the dette ne rane the tame clon athe mde aif rcv (ran oer hand tral der! vers especie) The ontrion venus od it nese syste eieuatin cet Yom teeta eon inereaes th bloat ust te teri erenily metabotzeby he oer folong rl aniston (ree 8) loos nw to aterent regen ofthe resine|s ret eta to he metabo acy fhe assed mucosa Creare tu ‘as acta absorption an aval mary drugs ough he esabshet afar concnaten gad. The sa mising has gener bod ow tan te clon de 9 te igh at of ace Yanspot required forruretdigesion an bsorion (rotees € and 0) Foc crugs antral the mort of absopton occurs ne smal rtestne due ope sua area ‘canta be sue ae fhe eum farsa han hal off anal eine. Tee, beeen teal acne rs Lupa stoner and more uorecctable (et Yattle oun of sto tan hat of ral adminsteed dus. This olen neessts more ‘hequent or reser vlume osna achew sri loos concerns inte abeenceof giant est pass metal, (rete ) Changes in nal los tow aecttne donerda fsa a, ich intun aft he elenaton of eal clewed rugs. Patios wi pared eal uncien have czas avast of substances that re predonrarty metaboedby he rey, thse patois may ‘evi lover doses te pevetanerse eects Edueatona objective: ‘Soaralbity isthe facon ofan admins dug that eaces he ssemic ren unchanged. Ons acrnstered rye he pra Ccrclston andre seco rt pss metal. Rectal arson 2 capa of pralybypsang fat or metbaier ars porate ‘frecalood flow erarsthe syst relaten dey Orgs iat undigo etenive tst-atemaabls ave crased Davaly he asters eth ialar) GB aren ‘rae ithe oye craton athe mile ad infor veins ane rma ic and iter pudendal vrs, espace). Ths operon f venus bos that neste systemic eeulation dec forte recta iereases the loavalablty rps at are erie enensielymesboized bye er ollourg oral niin (hoiee 8) Blo tow to iternt rages ofthe recast etd to the metabo acy fhe stents mucosa reser teed tow ates facifate abortion a ioavalbilty of mary cugs rough he exablshret of afavrbleconcntaen grat. The sraltesine nas generics ow man econ due eight face Vrspot Yeqed a ret deste and sapien (Ghoies Cand D) For ras minster the major of absoton occurs me smalrestne due os age sac rea. ‘nas the suoceatea the ects fr smal han that fie ralinesine Thee, atartion eal cists ras ‘ypaly stones and more urges (te vale anos foo) fan ata aly assed drugs. Ths en neesste mae ‘taut geste volune dosing ache air ood cenceratons ne ebsene of get et pass metal, {hoie ) Chanse inreralss ow afect he ger fab ie hich inten alec te enna teal ceed rugs. Patats wn pared ent tncten have sessed cavalo substances al fe resonrarty metabazed heey, hese patents may ‘require lover doses o pevetasverse ofc Eduestons objective: ‘lovely ne tation of en adminseed dug at eaces he systemic reuatn uncnangedOugs acne aly eh para relation and are subject rst-ss metaolim. Rectal aniston cpece of paral bypassing fst oss metboiom a popoten fecal lood flow eresthe systemic relation dec, Orgs tha undergo extensive fstzass metab fave increased Beavalbiy When arises ech Reternens + Fsipas lmnton Basic concepts and chica consemierces Pamacsoay GerealPrneipes Route f administration & beavalaity ial CaRC) aes Laue OL) | a-yerald woman cams othe pysican fo aelowp vt. Shewas dagnsed wth eunar ats 3 mares age and sae oo ‘menanerate tetany. Despte vest, te consis have several nous ning sites ly a equ avant gh uo Ine pan. Physica! eramnanon shows swing and tendemess ne ors oer hands ands. Eanecet i subeaquenty added ther ‘reamentegimen, This riesieatons best characerzed as wich fe flown? ‘A. Cetautaceeeptaribody 1. chiere manasa! antoeay (Humans monaco anttoay © 0. Smatmolece recente saber OE Satie eer don ten ial raOo ar) - wa | a-yerald woman cams othe pysican fo aelowp vt. Shewas dagnsed wth eunar ats 3 mares age and sae oo ‘menanerate tetany. Despte vest, te consis have several nous ning sites ly a equ avant gh uo Ine pan. Physica! eramnanon shows swing and tendemess ne ors oer hands ands. Eanecet i subeaquenty added ther teamentegimen, This rieietons best characerzedas wich fhe flown? ‘A. Cet astace eect antbod (1%) 1. Chimere mane! ante (0%) Humana monaco anton (10) ©. Sraitolee receptor rier (13%) YE Saute receptor decoy poten 8) ra ialSI toe = Fanos! co a ~~ ange oreign varable regions) * “Humanized (human constant & : a = oe namtaTe Boe > thine] ae |immremndisea| er | _imtobrwocti | sob : Seb aa Ve - 23 co | soe : Hl > “oor | * 2 we | a SFE 3 oom oo usages conmasesan ro ialeee “vy wo | tee yyy a0 ‘ret |uman srs re shown od renturen pai ‘he The conpleeniy esr reper tho ores ontop ofeach ereooy Vewelinpretneiie used ony when the eign suntan bein wih a ensenant ‘p= nore abe pa pra noe Etaneeapt estar nero ctr (TNEa) nor eso mehoreatto est nosey eer erat athrt in patie he have fled etorenate alone. sa fusion protin nk 2 solite THF reeror te Fe conponent huranimunogccun Gt (G1). Etanerap edict lage! actly of TNFa acing ara decoy eeepor the TNF-recepor component ce he sponge fo ‘ed TNF cand ep any on funcona TNF-a ees, wile he Fe componert saizes the colex Phamacouical eoreanies provide the riche names fortblcal agen he sixineaes whether he mesiaen is amore aru mad) a feepi meseeue (eee) a araseianbte (nd). eraser antes, wich ate Me ages goup opal agers ‘bo use tax nares he Wpect Gt 69, bata or me stm) and te era (e, human of mouse) ro ialar) GB Etmreapes2tunarnecrss tac apna (Ta) aie acedo medoveatto Yea moras Severe hewn awts pais ic have fled methotrexate ae. sa lon prtwin inking asclble TNF-a receptor oto Fe component of huran imurogcculn Gt (a'). Etanerep recurs he bologcal act of THE acing 3s. decoy receptor: the TNF receptor component cs hea sponge 1 ‘ed THE cand eapit any fom functional TNF-0 ects, while te Fecomponertsiaizes the cole ‘Phamacoutcal corpanis provide th prfixfthe names frblojcal agents he sfikindcates whether he esate is monolna amid (ma), a reese ec (cee) or akraseinhbter (i). Nerocerlantoses, wich are Meares qrcup cf opeal ages ‘aise re inthe names the pect ot en, baler or me stem) andthe erin (e,Puman of mouse) (hole A) Rema (Rt:ximab) isa china monecioralatod tageted ans C02, aca ecaptrfound onthe suas of Bea. |susesto treat CDZt+ rensegkn'smphoras and oer diseases atts excessive Bel furton (hetee B) Inia atx mab) is chimeric onesna ansbedy targeted agaist TNFa. tis wedin th ueanont ofa nuber of ‘auommune dssases (a, here aris ard Crs disease) (rete ) Cenctzunao pega (Ceno-+21ima) sa pevate (pce) humanized maradona aready hal tages TNF Macs he Fe ragon whch lps mninzesconpemant action and cokmedated ctx ht can occur wih cher an-TNF-amedicstons ha cetain (hele D) nsind (ati mst is used eal pei cane ncang Pada cvemosere poste eves myelogenous euler and poste gstonssinasroral umes. is an xample of smal-mokcule wos nase eee inhib Edueatons objective: “The affix of logcl agent nates wheter amedcaton 2 nonodonlarbody (nab) a een moc (ep) er kinase nbc (nt). torecna artes as ice nthe ranes the ye of target (eg, backer mmne system) andthe ign (a, han rouse) Phamacsbay General Pincibes Drug srucreand properties ‘inet osm we ra ialPee og a ow were construct aterappcatn of eet agents. Curve A represents he elect of bethanechl a pute henge apes Biological effect Log drug concentration Which fhe cues mest ke represen the eect fbthanecto) ater apicaton ofa reversible compete anno? Co ialLog drug concentration hin tne ere mest ike rprsent the etc ctbamanssna ate aplesbn ota reverb compete anagons? o GBCar Le Ce aren Log drug concentration hin tne ere mest ike rprsent the etc ctbamanssna ate aplesbn ota reverb compete anagons? > A Gneaon a B. Cune 8 (3%), a e consen g See eT come ene onites sos oe Toco ss E — oene i Gil ‘petagonists re agers bin to but do ntact aces. Aragon can bo ier campeveerrencoMpeTine. ComgeONe ariageiststird he eat sae receter bing ste as erdogeneus or erogenous ago, eet peveing apis ing and ativan ofa eceptor Compete artagenism can be revel (enc bond) reverie covaan Dod) Tec of evs cementve antago canbe cvereame yg concertaton fant, when cause dsrecement oe tapas om he ects Nencompetve aagonsison he cer hand, arto eceptos at ast othe ante rary aponstbndrgS, ereby cause 2 cantina ota) change inte rcp get at modes he agin nding tana pees gon bedeg, By Beng 8 ‘iteen st mente agent roneampstine antigen ar abso eran nso he eer sven un hgh coceranan of aon preserebecause he agents unatieto dciacerenconpete antagonism the rece “The question has ark how he cune er bathaneshol Curve A) woud be feed th itoducton of arevesble compesineartagaist A raverstieconetinearazestis expected requ ihe doses of the ul agonist (behanecho) tobe preset to achevethe same fe at ‘ochpaint lng he eve. Fencip ofthe orl statis ced te rearoncan leach he sare maiim eet Thos, the log dve- ‘esperce cave te atu ago combned wth a etersinecempettnearagens ui exis 2 partes Behe alog. dose response ‘re. wih an ineasein be ED anno charge nthe mur! Ena (hoiee A) uve A's the dose espense curve eho org agp gin the absence medi such satspnists (holes B adc) Btn Cures 8 anéC represent th ee of adding orcompative aiggontio th agorict Noe thatthe EDs unetanged 12 the ED fer Cunes A, Sand Cone ae eat sane ag dug cncsiaten) Ths a dstrgushag charac of rnorcomgettie anagons. The maxum eect Ene) of Cunes® and are edies because the ancompeste artagonsthas efecely ‘ede tne munber fraceptars avalible fr bndng. The decree in Ea, wl pend onthe dos of nancampatine rlagant reser andi states by he difronce between Cunes B and, where ahinherconcantatn of antagonist pesatin Cane C tan Gane. (rete B curve Dmustates argued hm ne dose esprse retonsh tute shits nt apa shi because ne shape ofthe Carve irs romthatofCave A witchangeein bth Eng ard EDip, This nat chasers fay si antago elect a ay be {heres of accra mute yps of aragons. ial> a ic # > @A S preserebecause he agents unatleto dsiacerenconpetoe artagznss om the rece “The question has ark how he cune er bathaneshol Curve A) woud be fected th itoducon of arevesble competineartagaist A reverse coretineartazenstis expected requ ihe doses of the ul agonist behanecho tobe present to chevethe same fe at ‘ochpait lng he eve. Fenaip ofthe orl statis ced te rearoncan leach he sare maim eet. Tos, elon dve- ‘esperce carve tatu ago combred wha etersinecempettne anager il exis 2 partes eh alo. dose response Care. wih an inceasein be EDs anno charge nthe mur! Ena (Chee A) uve Ais the doseesponse ceo the orga ago gin the absence feds such satapnists (hetes B and 6) oth Cures 8 anéC represent ihe eect of alding a norconpatiteanlagonl tothe agonist Noe thatthe EDs is unetangea 12 the ED ter Cunes A, Sand Come a me eat sane ng aug cncsiaten) Ths ea dstrgushag charac of rnorcomgestie anagnsm. The maxum eect Eng) of Cunes® and are edices because the ancompeste artagonsth efecely ‘ded ne number freceptars avalible fr bing. The decree in Ea, wil pend onthe dos of nancampatie antagonist reser andi states by he ference between Cures B aC, where ahigherconcantatn of antagonist pesat in Cane Ctan Gane. (rete B curve Dmstates a rgwar hm inte dose esperse restonsh tute Shits neta paral sha because ne shape ofthe Carve irs romthatofCave A itchangerin bth Eng ard EDip, This enct charac fay si artageit fect a ay be heres of aang mute yps ot aragons. ‘Eéveations Obectve: Eee eel eee emt rae Site rortin then ose resperse cane, stating anincrease rth EDsa, and 2) nochange re maxrrum fect Ena) * Gompesve=change EDseshi int roncrpeve=change Ena =shf dow Phamacsiay General Prncipes Dose espense caves ialRC) aes Laue OL) ‘novel anretoval medication, Drug, bing deeper resig pats wh HIV icon, Intl sues sow ah a of eae fale duet continued vel rotation ine ban However eat success ates erove when Gru X conte wlan auart pert. Das compang fe two mediate epmons is shown nthe cle cw. Drag Xenly —OrugX+ adjuvant ‘average cerebral spinal ls (CSF) vir lad (1 manth)T0S0copesimt eed capesit, ‘Average CSF wal ead (6 mont) ‘0copesint —unieecstie Average serum concentration f Drug ssorgm serait ‘Sesexen ne cata, me aquart agent mosh proves alcool tough which of Metoiowng mecransns? A. Beckng estpas metabo ©. Omang ad ow the chad pls © 0. matey censaremacranspones © & Reasrg gomeruartnaton tte Co ialOo ar) - wa ‘novel anretoval medication, Drug, bing deeper resig pats wh HIV icon, Intl sues sow ah a of eae fale duet continued vel rotation ine ban However eat success ates erove when Gru X conte wlan auart pert. Das compang fe two mediate epmons is shown nthe cle cw. Drag Xenly Drug X# adjuvant ‘average cerebral spinal ls (CSF) vir lad (1 manth)T0S0copesimt eed capesit, ‘Average CSF wal ead (6 mont) ‘0copesint —unieecstie Average serum concentration f Drug ssorgm serait ‘Sesexen ne cata, me aquart agent nosh proves Wacol tough which of Metoiowng mecransns? 2 1 aa eee rae) = 0 eee HES) = ©: eg tee eps = YD. Intutiting cetuar eux transporters (505%) Da Rear gamer aan tn 9) : a amm ial Coaie et uber hero ry ‘The stun ess show athe basal fd (CSF) walled eel mans ovate when sbjects te veted wm Og X are bt ‘becomes undetectable hen Dr Xi combined wi the aunt ager. cause average serum eee ae lal equ bees te 2 oops, isk hath avant meroves the eficacy of run Xt neasng fs abiy © peneat he blood ram baer GE) uaryaugsnavea ctcut ime cossng he 38 cue oe presence cl spacazed endo cls wih vr Nght needa neon Mt ‘fom phys bare separating te CNS fom te orci. In aden mul anspor protons, parca -yeopretln re hahy ‘exessaontelumns mentranecf an capil erdchea cele. P-pycopctens an ATP-ren efx ump that co} removes wide range of substrates fom cals, ncuing ran commen prescrbe hns(a, ariocs, munosuppessant agents HN prtease anaes). ‘ns4Vinfecor, por penevaton of ariretowral medications alws he brn acts an arto sanctuary where wa epson can ee ete ee ee ee aes ‘'copretn hbton can improve drug delivery tote CNS. Fg}ycoean anspstes ae ako fundon he apical sue esc {ndcan it dug boaalaity by purieg he rg back tothe rtesina lumen. However ahibton paca can have a varable ‘fecton serum erg level, 2 reas bcavalatiy stn coursed by noeacederg reson (go he CSF racer canaries) (holes A,B, and) Reduces rug metabsism or deceased excretion cous tery improve Gry ficacy by iceasing average Serum uate However nts exerners, serum dug ives reas byeiy 10 na -2) wth zaamnistaton fhe gant. Ts ina incease n ug cencenatcn set reprsertave ofa snfeantchangein dua metabeldearance parameters ands uni feat © nceased S35 eration (Chole ¢) The chores ste ste of CSF producton ae can uncon as an aerate entay ino the ONS. However the excreson of ee eee ee ele ele Eévetions objective: # syptin sacar ban pay eon es Gace obra rt) ate aie getsoe a 2 forma physi arr separating the CNS tom the rein, In aden rule perp gleopoti, rhhy eapesseson Melumnalmentrane ct xan capil eres ces. P-gycopaten san AT ex pump tha ce removes wide range of substrates om il, ickcing rary cone prescrbed dus (9, arias, mmunosuppessant agents, HI tase inher. ns4V tec, por penton ot artetoval medatons alles bain 1 ac an antics sancuary what val pate can roseed unenaens fainsng ne deiepmenttresstart evans. Neos of npacsng ns BS ep, dripon ofr ancnons, pe ‘copretn ihibtion can imorave drug delivery tote CNS. P-ycoeten anspres are ao fundon he apcal sae of ences ‘ncan iit di oma by parsing He rg back nthe esta uren However nhiston of p-ghcopaen ante arise ‘ecto seri rug levels, 22 eas evasion enurned by meesoad cg arent (a io he CSF race cemanent) ee ee eet ee eee ‘uglesels Homes nts experimen serum dg ves reas by ely 10 (2%) wi coacnnsaton the adja Ths ina increase n drug concenraten sat eprsertaive ofa sgnfcantchangein dug mtabelecearance parameters nds ule tea 0 nceased 886 eration, (note C) Te ceri pens ete te of CF prodicton ae can non as an atnt nya ihe CS. Howe he xcreson ta ‘uosane by he enor poe srcty depart on chosen ow dra sea fo wus rine he arson ota pancsr ‘sisiceintothe OS Education ebective: -gycopcsen ian fn pur curd on brn cailary endo cls (pa fe ood an bare ans ade rarge subs =es from extern the rin. inhsiton of ayecertn can nerve dug elven te CNS Pamacsbay General Principles une of stn Co iallet toned oe large, rtnatoral ug corporation cant ps | ical al valuta he aay pete and phamaccknt ropes aa awd ‘leaned to eat etactyeplpsy ntl sues anni stoned hat he dug unig extn reanaey by eer 2 ucroniatonbypresuts tat are pany excreta bya sneys. The cue Blow demonsats the glucan ae ofthe rg ver Wie rage of doses Drug glucuronidation rate a ey GB aa eyDrug glucuronidation rate aren ooCu ee Cn Os) Drug dose uWord Which the folowing isthe mos accurate statment atut ths ds meal? OA Acaraant proportion ote cig metbomed pas pants © Bewanstrmaton ce aug eases nea pant? ©. Metals bein swich io er-er nets ou pa 2 © Thertectang atsbolam set cepansanton aes tore pnt | 5. Sealey one ag snehes plat 1 — eyCu Ce Drug dose uWord Which the folowing isthe most accurate statment atut ths das meal? ‘8 Acanstar propeton oe rug metabozes pas pants (7%) 5B. Seavey cine dug isihes at ont 1 (5%) ©. Beuarstematon ct ne aug ceases rear po 2%) VD. Metabetam begins sich to 2ee order hinetes near port 2(47) Therate of hug metatolam snot dependent on des before pont (8) gies ro oasce ovzazmen Soro LW Sr wescorcy parca a eyBae ee aren . > Zero- and first-order drug metabolism Zoro-order kinoties a 20.mg dose —_40-mg dose First-order kinetics | 20.mg dose 40mg dose aama 7 rns 10mg 20.mgdose —_40-mg dose 20.mg dose —_40.mg dose Same amount ‘Same proportion metabolized (10 mg) metabolized (50%) Ti Unmetabotzes traction ae % 2 © 2> Fr Le ee) aren ‘Te rg under mvesgaton gucurnats ty he nero wate sable products that can then be ees by the Haney The raph above ‘rows tow he tate of erg gucurnidaton changes win essa tu coses lower nse, quent af ry conde famed “recy rperoralte he ose aemnteod (25 mor ofthe drugs asrnserd, move rug-gururonid i peeicad), Becouse a fwd ‘roporten duis converted 1 theretabote, is ety potion fhe rap reoresersrstorder ints. ‘As be ecive tes on ucronesanslerase become stride Grup uci a does et continu aris with ireuing dose ofthe ‘sibsrat dn, Atti part (Zon he gph the nts change tom -o aee-orderkneos athe rah els ot 220 spe. Wh _zso-der nets a eonstantamount tu is meatoed and elirte per uni of re egadessfis eoncetatn er ose 2a andi oder kinetics can aso be represen apical by showing the decrease in du concraton ovr ino er asl ose Zerocrder metzbotem inca by a rag ine wth ngaite Sope (ed amour mira Pe unit of ne), Wheres fst oro ns ante’ as anexconntl decay cave ed poporien elites per uit ime) (hole A) Ate pint 3, the curve remains fat inca at contre amount dug is metabeed per unt me rgares ofthe dose, ‘shes doses re acnseed, te propor hat convered the metable becomes sale (i, te propeion metabolize non= corte ter pant) (note 8) leaaistiy the facie ofan rinses rg hat each the stenc crabon unchanged, sual eceares wih _2isaion due to neat asapon ad frst acs mettolem cared io pareteralairisatn In his ase, Nhe doses fhe rg ata hae geste biaratably eke toe stron ofhepatc manos, (note ¢) Api 2,betarsematon (le, retateen) ofthe dus Beis 0 swich fom rtrd erode nes due eran ‘stuaion,Hovever drug metal gees roto. (rote) Before pint, rg tab proceed wa frst-orr kes. Ther, me uy matablzan rte cea sige” doses araannsioes Educational objective: Instore kinetics, aconsant Faction (er Erpeton of ups metabolized per nif te, <0 a arount metsboies changes based onthe serumconeenaten In zer-oer kre, constant amour ef tuys meaboed per uit of ne indepedent of eu evesZero- and first-order drug metabolism(Ou CV) (reactive sts on ucronosanserase become stride erp fucrnide ae does ot conn ois wh easing dose ofthe ‘ices og. Ath pot (2 ont gon) telaneos change om sto nae-orderknaieanathe graph vel 928 spe Wn _ze-oter nets a consantamount tuys meatotes ani elated pr unit of ire egaress fis eancenton er ose 2ar- adie oder kinetics can aso be erent apical by showing the decrease in du concnaton ovr ino er asl ose Zerocrdermetzbotem inca by 2 ag ne wth naive Sope (ed amour mrad pe unit of ne), Wheres store ns manfet as anexconntl decay cave fed poporien elites per uit ime) (hete A) Ate point 3, the uve eas fat ncn hat aconstart avout of dua is metabeied per unt ie vga cl the dose ‘As fer dees are acrnsteed, tho poperon hat conver the metal becomes sale (the peparon meted no. cast ate point) (holes 8) ically ste facto ofan tinistered drug hat each he sytemccriabon unchanged, usualy ceases wth ol _2omnnisation due to ncampte soon ard rs-pass metztolsm cmared te parenteral aniston. nis as, ihe ses the ru ae ey have greater arable othe stron of hepato, (notes €) Api 2,betarsematon (le, etabeen) ofthe dus Beis 0 swich fom rst rer erode nes due eran ‘stuaion. Hovever, drug metals goes roto. (hotee€) Before pint, rug metabo pocead Wa rst-orr kes. There, me rug metablzan rte inceases shige” doses arcaannisiees Educational cbective: In etorer nee, a conse acon or roperton orp metabo par nt or, one ant stones change ses onthe ‘serumconeeaten In zer-rer kes, constant anourtf uy s metaboed pe uni of re nependent of seu eves Pramacsoay General Principles Drug metabo and cerance ra ialOo ar) - wa aren ‘Acinial lis tng cones aaa he say areca a foe erapy i weareaciny Ci escase Te madcatons 2 ‘moraclea arody gan! he ony, which hs maton of Tyapteyls ino e mesial parenchyma ad produces Agu {secs annonce. Patents wna rave ste, moder eevere Cahn disse ang naealedconverton herp) ae eros Inthe su, Many ofttese pater have real oc hepa Osuncon an some take cher meio that fect cochroe PEO eres fhe faoning che moe appcpate doa urinert int patent poston odaneae rug tty? Hohe ose in patents ang cytochrome PA50 ncicars oe Lower dose pars wih oceased omens von Lower dose pater with eral tublr dsurcon A 8 ©. Lowe dose paterts wih heptocettarestuncion . ialpeer d A ee ‘Acinial lis tng cones aaa he say areca a foe erapy i weareaciny Ci escase Te madcatons 2 ‘moraclea arody gan! he ony, which hs maton of Tyapteyls ino e mesial parenchyma ad produces Agu ‘lecveaintarmatr fc. Patets who rave che, moderato cover Cob disease and nave fale convertonal heap are ero Inthe su, Many ofttese pater have real oc hepa Osuncon an some take cher meio that fect cochroe PEO eres hfe aoning the moe appcpate doa urinert int tert poston odaneae ug tact? ‘A Higher cose pstet lng cochoms PAD nda (178) 8. Lower dose patos wih decreased ore fitaton 21%) ©. Lowe ose paters wih heptocetiardystincion 21%) . Lower dose pases with ena uur dystrction 8) ZO & Nene ard cen 2) S oe oh esmone 2 nun 2 | omnes tn ese tee pours ay mara nkenetntena aos ss mn es 2 | carSimsitn nnn avenger hee ar artnge pane ne caa ‘sace and blocking deleterious eceportracionsoiagerng.aentetonc mune response aps treat els Because fh age malecUa si, mAbs ant b adnistre ly ar mustbe given Wa intravenous subcsncousirranusclar roves Urikamostcther drugs, mAbs ae not eminated by hepato renal earance, ut ete ove omtha bo 2 ery o! ialport Nd A ee Monoclonal andbodis(RADs) af edo Uesle Gorag val aha lukeralynehaT elena) ang aloe Goeases (@3, Cot disease, euro ates}, The therapeutic ee of mAbsisacheves by cing the tage agen mt lama onthe cet ‘suace ad locking deleterious receptor itractionsotaperna.a enters immune response apis treat as ‘Because of hr ge msec sa, mAbs cant be site rly ard mustbe gen Wa inraenaus er stbarencousinrawuscuar roves. Unikemestctercrgs, mAbs are not eliminated by hepato rena sree, but ae nied rernoved mth boy 2 prerary + Tat messed dug earance mos decid gant ol surface anges ideo mterazaton(ecertr meds erdecyose) upon ‘ngtother gts, renown them om th ccuatin + Nonapeiie clearance Immunelbuin are convey isken uo by retical macoshages (va bring to Feces) and ‘scien els ra neyo) ‘once maiz rimunoplcirs ae etabozd ino ano aed wath soso. ne ae eet * ‘math acitate exceton tthe gta he une oe In conrast, menunoginuins aft etablzed by ese Stns, Dut er 2 broken dowaby pretaoyc enzymes. » (roies Bando) inmunalcbuns ae 0 age undp Sbstantl Raton athe omar basement manrane and ave Nat seed 0 Dy erenalubues, Theo, ent suncen does nt Santcaty fe manoconal anit clearance cB ‘Eévetions objective: = Marasoa arboes (bs) arene ema by hepane oer Seaarce. Tete no dose ausnent nacessary wth pared 2 nepatcenaltrcion or use cycvere PASD nde AS. + Quantieaton of xG moneorl abodycleancoin ees ialpeered A ee Decase ol at age necda’ see, mAbs cael besonvisleres aly ad MuSlbe get Wa FaeTous of ScuareOuSSTASCUS! roves. Unikemestctercrgs, mAbs ae not eiinated by hepatic o renal learanee but ented reoved mth toy i 2 perry + Target mesa uy coarace: mAbs directs against col surface angen undergo mterazaton(ecptr medias erdecyse) upon ‘ngtother gets, renown them om the cain + Nonupeiie clearance Immunglbuin are convey iken uo by reicloandeal macoshages (va bndng to Feces) and \ascirerdetell ets va nes) ‘once maize rimunoplcoirs 2 etabotzed ino amino sed wath sosomes. (Ghoies Aand @) any duns undergo modfators bythe etchrome PD sytem ard subcoqent coiaion reacts win hepato ‘math acta excseton tthe gta he une Me In contast, memnoglnuis afr atablzed by ase sts Dut ee oten downy poe enzymes (hoies and) inruncoehune ae age to undege stant atonal the gamer Basement manrane andre nl eceed Dyterenalubues, Theo ena astncenéoes nt sncanty fe manera anibty clearance ‘Eévetions objective: Morescaarbodes (Abs) arene eae by hepare oer seaarce. Thefts no dose austnent pacessary wth pared nepatcenal icon or use ccycvere PASD nde AS. References + Quartcston of xG monctoral antibody lea Phamacsboy GerealPrneipes Blog agers ialf= fel oie ~ eo S eO) a aren ‘A new rts dovtoped fr he vesront ot iecons caused by estar gam peste ccc has avobme of eibuton of HL tis climate ty rstrder nes anahasahatieo 0 hous. Hlgven by 2conuousifuson aprox how much te woul ease fortne rugs achieve 965% plas seay ane concertton? ial Coes a b> 6 ar) - wa ‘A new rts dovtoped fr he vesront ot iecons caused by estar gam peste ccc has avobme of eibuton of HL tis climate ty rstrder nes anahasahatieo 0 hous. Hlgven by 2conuousifuson aprox how much te woul ease fortne rugs achieve 965% plas seay ane concertton? A torus (7) 8. 20rous (1) ©. 30s (13%) VD. hous (7%) f= fel oie ~ eo = tn = | cumasrtame nisin ai mt ton ts conn de isis he te 2 | Skeiscmoenmconeshctetnnes Ths wow the wotnsch Oar harm ehatetOhar eSain Sm | Serena ae aoe cnaan | esos Se eee tee ee Phamacsosy GereralPeacples_Serumdupievts and hat ie . ial CoS eO) a aren ‘secbonal aca oan sce vessel ater appicain of te cg. Thefolonng.unes are ttaned \Which othe ong sth best statement cancering the elects ofthese duns? ‘A Drug has lower poten tan Dg 2 2) 8. rug 2s higher afin for ana recepor than Dg 3 © 6. Orn t demensvates the hahet cacy © 0. dv 2am Ons ind eet ofahavecens Drug 2and Dug demonstatea sini pteny Co ialcece BY Ht a ee ‘stcbonal aca oan sce vessel afer appicain of te cua. Thefolonng.cunes are cttaned Dug2 bugs Log drug concentration Wich fhe alongs the st saan concen the cts these de? = OA ng rslver pone rsx? a © & Onn ashe att abrareepos than On 3 = © 6. on dene rite 3c) OD. on 2ondDug3 bt itera tabasco eee Co ialaren Log drug concentration hin ttn foluing etn st enament cancemng te eet these das? OA Og 1 astower patney an Og? © 8 og 2nasnigner anny tana eceps han Deg 3 © © One t menses ne nares encacy OB. due 2and ngs indo cteetls of aha recopts OE dng 2and ng demonstrate simiar tency — oFA Cu Lt, Le OS aren Log drug concentration hin ttn foluing etn st enament cancemng te eet these das? ‘A Org has owe potency nan Dg 76) © 8 rug 2s he attr apna vecepes han up 3 (75%) ©. ong 1 cemensuates ne ghest encay (4) . Drug 2and Di nts dirt cof apheveoapes 8) Dg Zand Dug demonstrate a simir potency (5) a 6% 5 secs ozioava020 = Wess a oaren fica and psn ar toms that are conmory uses nice contsed In phamesony, creo the isc bit of > let neck. such as recent acvaion or dian ofa vse as deserbedin the ueston stem. Isa meas ofthe masimum cling of ‘ach ned) 267g wih respecte a parr shamacodanic nd pan. Fer exanpe, locp duets such as uosomide or burton cause reer ess of rates than any haze crete, respecive ct dose. Petey, onthe fer hand esto the dose of ug thats requedo produce agen eet The poleny of aduais pmaiy afd by he iy oft us ris recep andthe amount of rg ais abo reach the tga sues Thee, rps ihat in thor receptors wih 3 hip ainy erare tere able to gan arcesst thet age sss wil have rewer potency. The pclency ferent ages canbe corpse by determing te dose fg ais equred to produce one ha (50) othe maximum boi response. This dos is known a the EDs “he ower ba Edy ac fe re potas. For example ara snd dusts, 2g of hota and Sg iehasone peice iniar ops bled pressure (sma eficay). tucson equres over dose crower ED, than HCT2 9 aire slr ec (ther glen) win respect he eso, rug 2nd ua have sila matmum ees ec). A much er dose fun 2 remit fo pode he same efect stat san win dg 3 tear, is more ptt an cup Sanches lower EDs To achieve Mis ger pany Re ‘ning of rg 2 # eestor atin) muetbe erin hatctaig 3 holes Boro? mete eter ate to reat are (@xneraten) tan dua (Chote A) Org thas ger ctr than Drug 2 baat tow ileal acy can cause the same eect wih mach lower cencetors ‘fori. Howbuer tes nt esen te same mmm eset D092 (rete ¢) 079 | cemensuates nelowesteicary c2ing of Bouya eet oh Mee gs raped. Lower encacy may De 2rsut ot paral agonsm and cer fecors. (rete B) O15 and 3 ene a partie ha te itgcal tats ening Sen eeacy bt erent peerey (The shapes ‘mer apr are erect bt at eet dose anges) Dug 3 may contain te same base phamecaigc agent as Org but wih aconpelne srtageit ted i tus, he Eq he sare blhe EDapnhgher.Acanpetive antagonist wou bro the same locaton asthe angaren learaonepecuca siniar dps bod pressure ximiar fray, butcher requres over dose eower EDs, thn HCT2 9 cause a snr fe (her peter) itn respect the question, dug 2 and dg have sil manum es effec). Auch owe dose of dug 2 segue a pode the same eter 25 at sean wn ug tee, is more potent an dup Janae aver EDse Toacieve is gh eany te ‘dng af 2 ts eect) ste niger han that cug 3 (Choice Bo cig 2 mt at eo eat age (Generaten tan dg 3 (Ghote A) org thas ngher pcre nan ug 2 because tow loge acy can ease e sume eect wih mi lowe concent feng. Hower toes et ese he same maxum eft s Dug 2 (ehcie ¢) Or | dementias telovestficacy ceing of tages! eet athe tee rug raphe Lower cacy may be ares aval agonsm and oher teas, (hole D) Drs 2 ard 3 iba pal shin hei elatie icogcal fess exibiing sia eficacy bt erent olercy The shapes of ‘mer gzers ae dental, bt eet dose anges) ug 3 may cortain the Same base phamecaige agent 35 Dr 2 but wh aconpeiNe artageist medi ts, the Ema he sare bit he EDaa shah. Aconpetve atagenst woud bdo the same ocatonas teen (roe) Org 2has aloes EDsp (eae poeny) an cg. Sam Rave equal encary ‘Educational Objective Eficacy sa measure of the masimumpharracodyaic eect achieabe wih actup. Fer refs the dese of rg thats eared to proauaeagventec. Ouse al br he eco wha Nghe ayo fe eer Sleo gan accesso he gel sss al Mave geste potency ower EDs) Phamacsiay General Prncipes Dose espense cavespal doa = oo) re CS) ‘Aveseaeners conan atovospeciv tty on bea cane ecutence Recs ot nro pas wih harmane ecto gost, earystage best cancer who ecaved gknart heapy wh anouten wee evaluated. Vatous dca demogiaphc an dug cncetaon Caavere anaes. A comparison pers wo had daaserecurence win tose Who remained carcr tee showed hat sone of he reaps paers ha lowe serum concertabons of enoefe and énycontamonfn, he acive metatotes oftaroefen. Which he folowing the most ly cause ch dss nfectveness in sabe of pater? OA Ratatat atc 2 dowrsteam sal ransice| OB ecrased hepatic Nacetranstease cht © 6 ety of tieprne metnrranstaseerayne . Oversresin of Peart inter cls OE Paymerphm ofa esha 45D eneyne ial opert Nd A ee -Avesarcher conan arazospectve ty on beat ance ecuenc, Rect umber patents winharmane receptor gov, fanpage east cancer no ected agar Merapy wn aronn wee eased. Vous ical cemgyaphe aug cnceeaton Caavere anaes. A comparison pers wo had daaserecurence win tose Who remained carcr tee showed hat sone of he reaps paers ha lowe serum concertabons of enoefe and énycontamonfn, he acive metatotes oftaroefen. Which he folowing the most ly cause ch dss nefectveness in ts sbect of paters? ‘A Acang maton acing 3 downstream sal ansauer (6%) 8. Deceased hepatic N-aeranstorse acy (168) ©. Deine of iepurne ethrransterase ene (2%) . Oversresin of Pycortein the mer als (10%) VY Paymerpham fetch ASD ancy (58) 2 tanaton = Cytochrome PAs (YP) enzymes 8 cup ot Nene-containg otis har response rhe mae ot ug metabolic a ‘cz presorntaly inthe ver Vanous CYP setpes ext wth CYP3A, CYP2D, and GYPZC ashe mest ache sone mvehied mdr rmetabolsm These ences genera uncon to deacate duns nd ciate excretion he bey by mrovng Water sbi, Home, Potymerphisms may occur no genes oss ks has crzyes ates hit eso of vi Teo Non here St PO a oens is Qt oz 2 ep ol Dane-coaning poles are espa or De Mat aug Mabel, wich ‘cms presorinataly ine er Vannue CYP stpes one sh CYP2A,CYP20 ang CYPZC ashe most ache chpes vee nr rmeabokem. These encmes goer urine deatate dus nd facia excretion fom he bey by mgrovng water sbi, Hoveve, {hey asometanole cen covpaunds a Mer ace fms Polymorphisms may occur ne genes otng fo hese enzymes, ater he expression or avy, Thee irptant heroes xs poor. interment and rapid metaboizr. erties aration n anna ass powes 2 amex een rap pein Ueamentencacy, andranmzrg odaty Troster 2 selective estogen recetr meds sein the veatnert cf estogen eep-postive breast canee sa pcg metabolized (6YP20 oe active metabolite, endosifn. Patri wth genic plymopisms reiting mpoorCYPZD ac ar enpored io decesced evel othe ace netaolte andhave ane isk sea apse (hole A) Aceon of dewnsteam sia vansdce pes, sch as KRAS, leads to achaton ef tarsipen actos aterm cel (un, Vdatone inthe KRAS gana ta aso he ewopmert fener and kngeanees. (Chole 8) Decreases actif hepa acerarsferase ress in a mised aby to metabolize dus ich as sora a _slonardes eangtaan escalate (Ghote €) Thpurne mahyvanstease i responsible fore metabolism of thopurnecempcunds such she inmunosuppresive un 6 rmerapesrne.Enemedefcenc lads ineease hu xichy (hele ) P-xycopetenisacol membrane prot ht ves etx of arumber cf substances outofte cl. Ovrepestion fp- jyecnrnin tumor cle hs been ones ae acai of mea eestance Educational cbective: ‘tehromeP450orzymesfundin the Wer ae espns forthe maorty of ug mettoism. Polmaisms occuring ne geres cot for ese eneymes est vous shenctipes ta erin thats ef metsbotsmndvcua dlrencesimphertpe ater weatent ficacy sr agtonity References + Cinealy elon one variatonsn drag metabolize enmes Co GB = aa eyprertN doat A ee Tener ehieacy, ang mina ey “Tone, a sects esogen ceptor moter un he esa of agen caper postve east canes 3 pay metablaed by (CYP20 os eve metabo, endoifn. Patri wh gens poymopisns resulting moor CYFZ0 acy er exgosed io deceased Inve othe acne rietbolta anahaveanigherrek steer apes (rete A) Aceon of downsveam sina wansauce pees, sch 3s KRAS. eas to axnaton ef wanspen actos Ra poate cl (7, Maton inthe KRAS gee re assorted wh he evelopment colorectal and ngeances. {reiee 8) Decreases atuty ef napa Nacrarsteras resus 2 dled any to metabolze ds such 25 saan ans Suboandes,eadng nan eased end etter) (hole €) Topurne mahyvansteraee is esponiblefor te esablen of hipurne compounds such ashe inmunosuppresive dun rmerapcpune Ere deioeney eats oereased dug ty (Ghoiee ) P-zycopctenis ace membzane protein hat ves efx ofarunber cf subsances outote cel Overepession of = ‘Education objective: = Crane F450 erames tandems of ug natin Poymachins orring he gees caro > tress ays eat aca pancetta wens eer ey » serge 12 References cay lar gence vara cg mesbleg eres 2 een » remecaooy Genel Puncpes — Pamecoperais ial CoSEZ oem > Eo Ee OC) ‘A grup otimesigatrs is prong an cxptmen designed assess gore varity in rugbicvarcomaton. A fued dose of sonics ‘vento group of vores, ane plasmacug concentrations measures ou housfoowng axinsaten of he dug. The eloning deisaen of sera rg concertanin hese et stared | j ‘aration of whic of te folowing processes roves the best xlanatn forte shed rea of he crie? ‘Concerta of INH in asm ial Ca= omamere SP ek ‘A Metaton (7%) 1 crontaon (10%) ©. Hyp) VD. Aeeviaton 60%) E Amine owtanon (5) Cu Ce ‘A grup otimesigatrs is prong an cxptmen designed assess gore varity in rugbicvarcomaton. A fued dose of sonics ‘vento group of vores, ane plasmacug concentrations measures ou housfoowng axinsaten of he dug. The eloning deisaen of sera rg concertanin hese et stared | } ‘Concerta of INH in asm ‘aration of whic of te folowing processes roves the best xlanatn forte shed rea of he crie?aren “The ate and exter of rug meabasmrcraly ves fom peson person. These sight ntpeseal vais inte ably metabolze rugs ae yal reecsed papal y auninadaldsbsten usaly ne shape cabal cane, when plasma evs of gare meas ‘ta tna time elon a teed deo rug Ts he reed hws Used to generae the ag gen ne uso str. Wn ast ‘ups, the major ppl fal win oa standard det end 0% f pep wihin wo stands evtons ofthe population mano asa concern. & snge pean hist raph inate tha te poplaon berg ested rossesses.a sm penet hn metboizng expat ‘A bina atscorenuus, hme cane, 3 hown nthe queston cam, esse he presence of wo apraenhy Ssinct runs win the uy popvaton and suggests ptarracoaenetipommptism incr meatier capacty. mother wos, he we peaks inate No ne of espanderstothe dg win he popdabor ne that apy conver the got meatle (cracred noma) and anther it canes he gow, ang to accurulaton che orginal uy ne asa, |soiais metabo by aceyaton oN aceon the hep ricrosoma sysem the enzyme N acetyl arsferase adi ‘teaquent enced he une, Te st and acon peaks ne above raph vpese aa sow aces expec Slow cess oiaonicd so etanolze ects) dapsone, yaa ord pccananige sty causing Secunda cf ese due 2 el. ‘Slow anja of ese drugs are at ineased nk ton Ft, whl fst actors may requ uch higher erpeue oseste achieve areapeutc eect {hete A) Metyaten an impart dg otansfomaton metiodta conse when prsebing digs such a axabioptine and meses, gs use inthe vestnertf some inflarmatr sors fhe bowel a shin (rete 8) Gueondatn 2 baranstomaton parway td tre metab of umetcus rugs 35 wea endogenous substances ‘sich a bliubn. No Beads hes been deserbed wih is patnay. tu conden sch a5 ibe syndeme he dstucion the ducrony arses system tat cat ead tx acuulation of some ras. (note C) ryt acus win erayns such a eeetans and amides, aol! mtalze by th pay. nd le does rote polymere eal, (Chote €) Avie nan usualy undetlan by mancanineoilates by BENE nate deamination. Near process metabo "ears nr ets Boda.envets dag slo, adgts acundton te orginal aun ine plora soins metab by actjaton to Waconia nthe hapa microsomal sys bythe rey Nactytarsfease adi subsequerny xceledin ne une, The ist and sana peas ne above ign reeset a ad sow aces especie. Sl cca oficonad ale table acta) dapsone, yaa, ard pocanamge sy, causing accundsion fee dug a el. ‘Slow acviatr of ese drugs ae at inseated ik of ton ees, whl fs actors may requ uch cher espe soso ahve a teapeuic ee, {hele A) Metyaten an ingoant dg otansfomaton matodta conse when presen digs such a axabiopine and rmercapeprne, gs use in the vestnertf sone inflamma sors fhe bowel a shin (rete 8) Gueondatan @ aanstomaton pareay uted tare metab of umetcus rugs 35 Wella endogenous substances ‘ichas ibn. Ne Godt hasbeen deserted wh is patnay, tu conten sch 36 Gite sycome mone dystuncion the uct ansrase system ta can ead xc acuultion of some rs (oie €) Hytclsieocaus win erayns euch ae eeeracs and amidase, Ionic net mtabolae bythe etsy. and lie does rnotexhibt okmeric etabelsm, 2] ena ene toy trey rr es on ene oe | emai oo aay RT tent eee: 2 | irae ean epee ep ees rhe eoy ey % | Snap psn sti vec epost sen | 2 | Sentiinctan Sorstvemae aceon soe | Pearce xmemciln Paces ial Capeda = oo) re CS) ‘Anewaningcsie anit is eloped nats beloved be parc efeceve agaist Peeudonanss. The wume cf Sebuton ofthe Gugismeasuedna grou of voces andi etemned be 5. This newdrug is mos key shave whic ofthe flow propetes? ‘A. has ow elec weight 1 eistponmie (. Ress retin toatamn ©. ish bared OE ftashiah oat beaaiaity ial: rn —_ 6S) > = ° s Anewanitosesbie nots deere ats betel pact eecne asst Procimorss. The vom cf erton the 5 | GuammmiaemnndlwinccvedaitemeditetSL Tusnevdur meni ohne wh ote awn orcs? ; 7 arr oo a © irre 205) = : eee ch 1) a YO ish bane (5) 2 resi ol bona 9 ote a a a a ‘Biplanation | 2 “The clue of ctr (fr to het velar cf ud no wch he ante aman of ug woud read ob nop = asvnuad to procice te cservedgleana concrtaton “The oune cf sutton |sdtrinedty aanitring agen aout Oy 2 the iewavenous rue an subseverty measure he inital pasa concern the dg. The fomua i as folows 28 Vs (U) = amount of dug given ma) lasma concentration et rug rg) ‘Te average tal bay waters aprons 4 les Oftal exact lume sabe 14013 tal boy water Wa Be ‘eave fd, pasa volun is abou 9, and ire fd makes Up the et. Ialy, th dg ere the pla compartnent yedenna produce te cbsrvedlaama concentration. Te voune cf suttonisdrminedty agnntaring agen amount Oy the rsavenous rue an subsecuerty measur he tal pasa concerto the dr. Te mu a5 ous Va (Lamour ot dug given (mg) / plasma concentration of drug (gh) ‘Te average tal bay waters aproumsely 4 a Oftat ees Md lume sabe 14 013 tal bay water Wa eaceua fd, he asma youre show 3, and sina ud makes up the ret aly th rg eres he plasma compartment) Me Wrote. rug has large molecular wogh, bound ers to lasna pret, or shih charged (ysrophi) thn the rg gereray ‘omar inte Dasma compart ad the wlume of srt i usualy was mth cas sbove abet 35 ers). He cus has 2a rmoeclr wet bats copie ican dou in tential fi corpartrert ote of te ood vests a wel sine irranaecar ‘Cogan. In these cases he vane often sao vaume a abet 1-1 es (para vou pls wll vue). ‘me aug nas a smal moeeuar welt aa also wnchages yaghadeeipaphie) hen he ug can ss cal mentxenes a 2h inraceliercomparment. These dre hae ho highst eure of detiouton (4 les). Orgs tare avy bound in he Sues cent he hotest votes of sibton cen much hohe an he tal boy water ale, because ese crgs accuse ready wthn cls thereby ‘maining low sem cance (notes A) the molecular weg of he rugs ow, he he rug wil indo ss pss hreuph ental ncions othe mista ul making the value of tbo at east es. The Vimy be higherithe da slo yooh. (Chote 8) Lippi orgs nat ey eros cl brane an serte nicl ise te ples and inereti companments The tencerey to coletihn ces es hese tus atigh volume ofitbuten| (Ghote 6) A crop wit a Va 45 L, wich appre the sare ase asa ve, skh be hay Seu asa tens sich seatburn_ Bring opis tens tre oretan ug nthe lana conpatnert na evel he fin of gis he etavaeclt carmen. itis run weer beune bum, would be moe hyo fie he mrstoum and aigher Ve woul be pec (chotee€) Bosvalaity sa messi of abseen an i unelated oe aston ot dug ‘Educators Objective (Characters cdg such sigh molec weg, nih pls roan dng hgh charge, and yaopty te trap te dug inthe pious corpatrert resuiingina lon Vs SU) ialnvacelua fda lasma vou tow SL, an sina ud makes uptherest inal the dg eres he piasmacomparen’ ye "eo. Wa crghae alge molecular woah, sbownd extensive to plasma preens,hihl charged fyiphi) han the ra gerraly roma inte Dasma canpanment ad the wlume of srt i usualy waste case above abet 35 ers). Me cus has 2a rmoeclr wot bats copie ican dou in tential fi copartrert ote of te ood vests a wel sine irranaecuar ‘Cogan. In these case vane often nas aol voume a abt 1-1 es (ara vou pls ett vue). ‘me aug nas a smal moeeuar welt aa also wnchages yaghadeeipapnie) hen e ug can css cal mentxenes a 2h inraceliercomparment Tose dre hae ho highst eure of detiouton (4 le). Orgs tae avy bound in he Ssues cent he hotest votes of sibton cen much hohe an he tal boy water ale, because ese crgsacculte ready wthn cals thereby ‘maining low pasa corcenaios (helen A) the molecular weight of ho rg, hen erg wil ind oes pass heugh ental jncton ro he stl ul ‘making the ume of soon atleast les. The Vay be cherie dg also yooh (oie B) Lio crs tendo ey cos cl anand and droid ous els and ites compares. The tenserey to colect ihn cel es hese uns atigh volume of tbe, ar) GB aren (Ghote 6) A cr wit a Va 45 L, wich appre the sare ase asm ve, skh ob Hay Sou asa pete sich seatburn_ Bring opie tens tendering nthe lana conpatnert na evel he fin of gs he eravacelt Carmen. its un were beune burn, would be mee kyo ise hereto and aigher Ve woul be pec (hoiee €) Bosvalaity s amessu of absepen an ulated oe aston ota dug ‘Educational Object (Characters ot drug suchas igh molecular weg, nigh pla roan ing, ngh charge, and eopiy tan trap te dugintne ‘asma coreatrert esungina ion Ve(@5L) Phamacsibay General Prncbes Drug suchreandreperies ialpee doe = oo) re CS) ‘A 3t,yeacald man comes te oie duet pssst nasalcangesin ard ramen The pater has asin aay mats ar ect ‘noted acoss te cout sta anew ob. Hs nasa symptoms worsened ater te move ane tae sng an ere courte anal ocongstant spray hat inaly proved promot elt. However, ar ew days, he ha reas the requenc ad number of rays er nos needed for deste spa corel On exarnate, te nasal utiates are woke an pale with cer rasalcischarge. Which {he feonng mechs eres he reaponie eh pater nctearedmedeston ce? OA Aerie ra metabo OB Decreased certainty © 6 Depletion of eestor assorted Greens increased recetritematzatn ial oos og a ‘A 3t,yeacald man comes te oie duet pssst nasalcangesin ard ramen The pater has asin aay mats ar ect ‘noted acoss te cout sta anew ob. Hs nasa symptoms worsened ater te move ane tae sng an ere courte anal ocongstant spray hat inaly proved promot elt. However, ar ew days, he ha reas the requenc ad number of rays er nos needed for deste spa corel On exarnate, te nasal utiates are woke an pale with cer rasalcischarge. Which (he feonng meshes he reaponie rhs pater nctearedmedeston ce? pecelrates ru metbasm (4) A 8. Deceased recent tint (31) ©. Deteionofreeptorassocied Gprois(12%) . 00. cent ene fetce pment iy) a ote Eos oe anna a nun = Example mechanisms of ochyphvana ‘iveerge agents‘ Recetr nahn 8 rian by anes Indreclameatheninstes [Depo of atachlarnes fom rave errs Co ialaren ‘Example mechanisms of tchyphy/laxie ‘aeneac anes —_‘(Recetriachetin 8 rimalzton by arene Tnirec smatienimetes __[Depieion of aechlorres fom reve errs ies Deplon f eed ls deceases ALDH acy & NO preston Deznepessin NO) [Deplston of VAF fom eh dogs lex (CPD = cree PUB eaALAI= maid ely daogeane NO = ale i vWD vn Wacrand das; AF Zon ‘Tas pane as mts mesicamennsa ae tote use ct anasal decngestant sy contaning an alpnaadrearge agonist (23. ‘onmetaoi). rata rpcaton fala agents indies vasoconeicon ceutical Dood veo inthe natal mcoea ed.chg norhea adcongesten.Atheug thse ages roy ect for spo corto, se fe wore than few days s associa wath bound tints and osogeexcaision det tachyphylals “oeane to pha stenere scangestas cel cy eo eee itamaliaon. Sh apna and bets astenrge cere ndego a conlomatoral change on gang reg, alung hen 1 ata heteromeric Gotten mvovedin srl ranscucion,Honeve, the change nceromaton ase est n he bra of area, apr hat reverts fre G pon actin andi he rece completa dat, fettatng receptor endogoss and aeplion fom cel sutace As dphaasteregc recess becone ceasing Sacealeg the boos vessels of eras mucosa, th release endonenous Cctechlrine no engin prose adenine Yaroaneicne simanan,Thereslong crgesionthnobea canbe reieved ely ‘on nereasing doses ch exognoue alia agonsts “Tweertnvves cessation oe cet ange, someines th se fiona cacstroneta reve severe mga. (Coie A) Aecelertd ymetablam can ado tance when aubanc aioe the enzymes respon or es daadton (2 ‘tecvenes P50). This mechs esponsbe or he race seen wih earcl and artes, ialPa ar) GB “This porert as rhntsmeeaneeoss Ge the use arse decongestant sy cetaring a alphaareeree SEOMSt (3 cxymeiaoin} Inranatal appeston fala agent indies vasconeticen cf suparicalod wees inte nasal mute e809 ‘rinontea andcengsten.Atheugh ase ages are hy ect x spam cont use or ore han afew days ascstd wth bound ins 2c.cosagececaiton 3 tahyphylais “leance to ah atenergcdecanpestans develops ac) deo eet intamalizaon, So pha. ae bis arena ecetors goa conlomatonal change on gand brig, allwng hen 1 acta heteromeric G pitas movedin srl tansducion. Honeve, the change cenomaton se rest nthe bina fares, apron ht reverse G prin amon andi he recap completo clatin facta ecetrendocosis and elton Fo he cel surface ‘As aha atone receptors become nes sare along the ood vessel of eras mucosa, th elas c endogenous ‘tecolaines no ega suftcert prone adeaustevasocansce stmlaton. The suing cangesionthnorhes canbe relved ony wi Inereasing doses cfoxozeous alba gon. Tresnertinvhves sessaton of ie curt decongestant, sometimes wth ve ofinearasal ‘tenons to releve seer npn aren (Ghote A) Accelerates rp retake can ado oerance when a subse nics the enzymes responsi for ts degradation (6, cptecveres P82). Therechanem reszonabe or he oleae seen wth shal aa aire (cnoiee 8) Decrease econ stint duet intacair domain maifeion en, phosshention) can pay ale necatr desenstiton Fovever desensiznon of aden recess beter exlane by he deczuping of Spots (ich are blocks by ares) and ‘subsequent eee niemalzston (note ¢) Taerance eastern apoiss cevoos de oth bring of aeins to soulsted ateeric receptors, preventing SPs ‘romireracing wth he reepor prt themselves do ct become deed cng Bs process (hole €)Parasympsta sulin che nasal mucosa caures vaso, inoasee sa oxravasston, ad simultes one rmuceus seceton. Pater wh nts medcamentsahave ceases praspathes fne ehyscge antagonism) at coerutes the i ‘Eéueatona objective: Actin of eon cer es ae ng od ecneaenen Thi of epee rte tec een ialthe oange nceromain asa esse br of arestn agree Pal eves ute sn ahora nse ep cample'a clan fcttatng receptor endoyesis and ceplain fom he cel surface 2s ana sere receptors become ness sare eng the oad vessels fe rasa mucosa, the lease ct endogenous ‘atecholines no ena sufi prove adeutevasocnsticvestmulston. The reste cangesoathnorea canbe releved ely wor neeang doses cf xczencus abs gone. Treanertinveseesatn of he curt Socongeetar, somebres wth use ofinearasal crcoseoistoreleve severe ampions (oie A) Acclratd uy mtablam can ado Wotan when auttance nauces the enzymes recone fr ts deradton ‘tecrrenes P40). Thismecha responsi orhetleranee seen wih etharcl ne barat. (note B) Decreases eso tn co inacear domain moasean eg, phsghirytion) can pay ale hese desertion, However desensizaten of srenepe receptors is beter exlaned by he deczuping of poten (ich re backs by ars) and ‘subsequent receptor realization (tetee ¢) Teranceo ater pois doviogs due othe big of aestns to sirlsed aoa certo, preventre pots ‘rmireracing wth the recep. proton theses do ct become deed cng Bis oces. (rete ) Parasympstna stulaton c:te nasal micosa causes vison, neases plasma oxiavasaton and sts andr rmuteu sceton.Patorts wh rns medcamentosahav ineeaces parasympathetic tone phys antagonsm) at corrbutes toe congestonttnetea Education cbjective: 2 ‘Acton of trnorge recaps resuts i aesin Sining and receptor itaaizaon Ths tec s resonate forthe tolerance sean a wi aha-aienerc (6, ceeogesns, ,asopeses) ana beaacenee (eg, ronctoalts) ants 28 Pramacsbay GerealPrncipes Spr tansucten Co ialrarer a b> eee g a an ‘Acai lis copa a5sss ne atectveess of novel fmuain of spn Yeah advance ns lang cancer. tty parc aerrdeml ase 2 ret cole sed chematerapyregenens Sibjcs inte contl am are ante [conven cesnin enerctherapy, wheres those inh sgermantal ar ave gen afomulson ocean ancapeuitdin osores ees wi at-epicermal rom actor eene (EGFR) abodes, Paes the expernerta grup are euro havea stastcahysinant decease nes uration conpatedth hose ne conel yaup The nonce of are fects a ao oven the expermerta (0up. Conpare i camentona espa ceranerapy,neneu aman rest Melo have wc the flowing eels? Deceased dup etx fon tuner ces Eshanced eotonc Toe spose Inceaced penetration tough dene eemeplas| nnn of uring angopensis Sete ug uate by cance cae ial Copoet Nd A ee ‘Acai lis copa a5sss ne atectveess of novel fmuain of spn Yeah advance ns lang cancer. tty parc aerrdeml ase 2 ret cole sed chematerapyregenens Sibjcs inte contl am are ante [conven cesnin enerctherapy, wheres those inh sgermantal ar ave gen afomulson ocean ancapeuitdin osores ees wi at-epicermal rom actor eene (EGFR) abodes, Paes the expernerta grup are euro havea stastcahysinant decease nes uration conpatedth hose ne conel yaup The nonce of are fects a ao oven the expermerta (90up. Conpare i camentona espa ceranerapy, ene aman rest Ml fo have wc the flowing eects? A Deceased rug ef Fern or es 6) B. Exhanced ooowe Tcl respons (6) creas peneaton rch dence desmopac (9) 1. tte of nar intucesangiogenese 215) Setecve aug uae by cancer cls 8%) Co ialrns Targeted drug therapy Conventional chemotherapy Activ targeting recone Oh ° cremotnerapy agent “ep. pln) ° ° Seater creas ct} Phra tacedcraherasy ans (9 cpl) are vey cod aoa rt ne eae fr many sol ters incu nal callaren Planumbasedcnatheany agers cpa) are widely sod 30a rat ine westent fr any So urns, ncn ners lung cancer. These ageres det DNA repleaon and have subsoil veto gant apy rclferang cls, Desai er fica nla ‘uno cols ther weislined by severe adverse ef en nero. myeleuppesion) hat occur de cramuaon win nomalisues(¢ oftaget eect) Neha that rote targeted dlvry the tumor se can hep mnimiae toc anc optimie dru response. nis exarele.cslanis| crcapeiindin oso fang naneprce cage that opathe ug anit ewteaton viral cela. The aon ofa pea gue act ec (aMEGFR) antbodis ne pasomne suas resus an anubodydru conga aloirg he ercapsdrug concen selectively bind to tumor els excessng high evs of EGFR ich fen overexpressed in rons ce lung career One ound heared complaisitomsize and egrased releasing meee dug ito he ceplasm andeasrg tapeedcel eat (Chote A) Orerexsessin of drug ef puns (en, lyons) by cance celsis amar cause of humcthtaycesetance. Efacgune Inhbtors can decrease drug exciton fom tumor ces a ptenta the eft of chemoteraputc Snes (rete B) Many cancers create an inmunoauppessie micoentorment at peers he wemune stm rm ePecvey ig te cl ‘an exance tons Te espnes spas timo cee ers wnt Bef sine chagrin ep, PD. oe CTA easton Inher) tate prevent el extasion (hein ¢)Desmeplasia,eactve owt of fous comecive Bes) acusin response io coin tuna ep, beast paceate Carcinoma). The dense rt issue acs a a msec seve, deceatng he peneraten of cheriarapenc agents. Chereesstarcs is more ey to ecu wth age ru cree nhs case, the ew eosora rman Wil be mich ger han nia cit moc, resign decrease deamolate penton (Ghote D) nese exresson cf vascular enetetl ruth fac (VEGF) wth umes sts lod vessel grow facing turer ‘excansion ardinresna he plete metastasis Ati VEGF abodes ep bevaczurab) bind VEGF ard iit taro: inced angegeness.Aineugh EGFR simdston aso pays ae inangegenes, nhs eas, he af EFGR anodes te wet fo tgeing purposes and may rt necessary nei he EFGR recep artboces can be stimula, hoy, arhave na igang eM peri Othe ‘sscnmant ate)aren dena gue actr eco (an EGFR) snebodis a eliposne suas reuts an anebody- drug conugate along Me cnzapsui dug conn selecvel bind ote ells eesang high evs af EGFR whch 8 en overeapressd i Ponsa cal lung career One ound heared rg eomplaieitomsized and egrased releasing eee dug ito he cferlaemandasrg tapeedcel eat (Chote A) Orerersessin of drug eflucpunes (en, Palyoncsn) by cance celsis amar cause of hemtetanycesetance. Ec gune Inher can decrease drug exciton fom tue ces an pte the oft of chemoteraputc Snes (rete By Many cancers eae an inmunoauppesse micoentorment hat peers he wemune sytem rm ePecve ii te cl ‘An earced etn espnse agaist tuna cos occurs wth the use nmune chacpoitiahis ep, P-to CTLA receptor Inher at ep prevent Fal exhausion (rete ¢) Desmoplasia (, eacve gown offexauscrmecive ss) acusia resporseta Catan tras ep beast, panceate carcinoma. The donee fre tse acs as a ecu Seve, ceasing he peneraten of cheriemarapeuse agers. Cheroestarcsis more eyo ecu wth ager ru cree inthis case, he ew eosora rman Wil be mich ger han nial cit ces, eter tie (Ghote D) nreasedexresson cf vascular enetetl roth factor (VEGF) wth umes sts lod vessel grow facia ter ‘rcansion ardinresna he plete metastasis Ati VEGF abodes (9 teva) bind VEGF ard iit uno: inced angegeress. Atreugh EGFR stmusten aso play araeinangegeress nhs eas, he a EFGR anes ae wea getng upeses an may rt necessary nes he EFGR recep artboces can be stmt, hoy, arhave na igang eM peri Othe ‘tachment te). Eduestons objective: eto conates improve cg eTecy sme toxcy by alowng conventional chemonerepeute ents ep cat) 2 ‘lec tret andl carer ete whl parr heathy cols, tageted dave) Phamscobgy General Principles Drug structure and properiosmy em 2 Tumernniba Toa & veces see Teal stays acvetod 8 dstoys estueton thermo se Q zoamin Q zona rest aa Turok U@ Oo‘neapssid dig compen selectively bind to tamer ells xeressng hgh ees of EGFR, which sen overspressed in ron-smal cl Jura carer One ound he aetos-t compiextsiteaize and degacedeleasg eee dug he cherlasm anda (agetdal eat (Ghote A) Overexpression of drug efx pues (en, Pavecpoa) by cance celis amar cave of chertherayrstance. EA pump Inhibitors can decrease drug extn fm tuna cels an pte te efets of chemotherapeutic ars. (hele B) Many cancers reste an immunosuppessiemicenvonment hat preors the mune stm rom eFecbe king te cls ‘An enanced cone oe espnse apn tire ces orcrs win the se of mine chelgsir isos ep, PDs! oe CTA cet Inhibitors) ate prevent Fal ekausion ar) GB aren (helen €) Desmeplasa (,eacive gown offerauscnnecive Bec) ocusin responses crn tums ep, bees panceate Carcinoma. The dense rt se acts 3 mcecda seve, deceasrg he peneaten of cercherapenc agers. Chereessance is mare ey occur wth ger ru ecmplees inh cae the new posora fermion wil be mich ger han nial clan moles, resunng n decease desmaplastepeeaion (Ghote D) Increased exreson of vcr enetelal rth facr (VEGF within umes stubs lod ese grow fciting turer ‘expansion andincesng he plat or mata At VEGF anodes op Reva) bed VEGF aura langjoneness.Alreugh EGFR sindeicn aso pays ade inangegeres ns case, he al-EFOR anodes te sed tgeing pupeses and may ret necessary rhbitthe EFGR recep anbedos canbe smut, inion, orhav no signaling eet epercing othe stacent sie) Education ebective: Arto dg cones improve dog eiesy ands toxic by slowing convenora chemoherapete ages ep cpa) 0 ‘sec target and learcer ces whe para heathy cols (fe tated dene) Phamacsibay General Prncbes Drug suchreandreperiesRC) aes Laue OL) A S-yea-old man comes one offer at annual pravertve vet. Hea aay tessa alps, ane ect saad lng 3 mecaten a as proved is uy rose, steezng, natty ees edly remaratie or decom ype 2 dabetes mets Snseczana.Hevenaton any omer maceabone. He does reuse tnacea, scone oriletonie.Expmiston anowsa ws arpesing man wi usted cheeks and lated pois. Ths patents sal exarraion dings are best exlanedby which ote flowng means? Ca ial5. Arageism ot H receptors) ‘A. detaganem of Ht eee (18%) \Y ©. Arvsgenem et mss esse (67%) 1. Aragenism orice eee) . Simaton fala ackenorecentos (178) Oo ar) - wa A S-yea-old man comes one offer at annual pravertve vet. Hea aay tessa alps, ane ect saad lng 3 mecaten a as proved is uy rose, steezng, natty ees edly remaratie or decom ype 2 dabetes mets Snseczana.Hevenaton any omer maceabone. He does reuse tnacea, scone oriletonie.Expmiston anowsa ws arpesing man wi fushed cheeks and lated pois. Ths patents sal exarraton sings are best exlanedby which ofthe flowng means? care ome LW rasa, Toate fet ‘planation “Antcholiergie oxy ‘ymotor Mecranim [Wotan ahare™ veouto nau Boy tempore Se Ca ialaren Wechaniom Hot ara hare ‘Sweating lado | eat daseton Boa tempeie nana denieaata [bey asa bonet reese cous maneranes, seat gana |! COM SCN 8 smooth made cnracten ad spent ton et |-Band ae a bat Paralysis of cary muscle & ns sphincter [Crcloniega, mydriasis " a a Fags anor a Pormeses loos ranbarir & aft ONS pahaays arena ‘ainda | conten Frastar naa ce | ieee atest node ‘Tas pass aly rg 2 et. ganeaton antihistamine 9 slpenttanin) wich ae coment eda beat anwormeta (Sabon sd etn of het ope. legs and set cel ead acres Fest gentatin arthitanines ae naspecte ond act a ntagniats ome eens charg ‘homusearnieaceylholnereeapor Thsicaés anicholinegecReci(9 fver unary rete, deessos snes, aered mera ‘Sas nbsp. the fushng's ily a coreensaiy response dsspae excess boy eat eo decreases seaing andthe puioy ‘Athauah commonly desrbed = Ht receptor antanonists,aitarines ae actly ere apes hat sb the receporin he naive . ial Capee dd “This posers ity hing rst-aeneration anthisamine cn, deena), wich ae conmeniy use er teat enone llages and mat cel ned doors. Fret generation artitamines we nanpecic and act ntngnits ome ecpers eck ‘memuseareic acwyleolne capa Thsieas aneholnarge Pee} feve una fetrien, deneasea Shean aered meal lau) nti patent the fusing nly a corpenstry respons o dss acess boy heal due deceased veaing andthe pupilay Glason ce fe rhtiin often sche tough coment desbed oH rcepto antagonists stains ae aculy ere apes at ate te recep ne nace ‘tae, H1 veces ae ound inte vasa enetelum and borehasnot mus, here hey medals vascular pemeabay and ‘oncheconcion, 2 el asin coral neous Sst where thy ae ricedinaerress.Arhisarinic eect rove nasal congestion, ficontea, reesng.andicing Fst genet arthsarnes cess the odin arr andcaie sofaton Ey carts. second (erator arznstamnes elias) are maf pene oe hstamne Heer and nave les pameably Eau eos an ame, ey ae genet es efecve Ran is-geerabon arth but have gaat ever ae ees (hciee A) Fshing and mydriasis ar ust aiagentn fhe cena recepor nl he Ht recep (notes B) H2receters reson pata as inte gastic mucosa HZataponiss lock gst acd ecretonby pata cals (rete D) cn chine receptors ae aun in sympathetic ard parssympsetc gangla and on shall misle ces ate neuromuscular junc. Nest receptor rapes, ecu) are ued induce payin reparation fr urge cr endorachea nuttin. Adverse ec incu hemanamcinsibhty (ea, pees) and resprater ssicercy. (noice ) Aga acrnorecepis ae aden scan ce nd neuons. Activate of ase recep eases anode tne ot their eater (causing myeras) and les ess (casing vascensrtin; pat acenerge aon (0g, ponlepine, oxmetazin) Cane usesn patents wh lege rns because ther asecnsrcive acon reces rasa congesien, However. eseconscton nhs ‘Education objective: Fis-geneaonahetomies ae nenspec andrea wih mule ecepes. curate msc recent. This leads article crac (0 eve, Tush yas, unary fetertn, eye, aed metal Sats) ial‘las ave ntiton ones chet Augh commonly desibed 2 Ht recep aniagois, stains ae aculy inverse apc se the rcepoin the mcve ‘Sot Hi costo we ound te vasa eam and beets msc, heey mace vascular peat and ronehoconticn, 2 alas a coral nevus Systm whet thay ae ivvedinaloess. Ahir eects reove nasal congestion, rorhea, reeang, ar icing, Fest generan rhsarines cross the od ra barr and cause sofa, By conta second ‘ere arthisimnes on tae] re more pecs the tari recep ad hve less een taugh he Hood in ame, ey ae genera es efecve Ran geeranonarahtamnes bt have gear eve a2 eens (Ghote A) Fshing and mys re ue tartan fhe chong cere, nthe Here 2 | moyen er tnsepa atin omc Hatt ge nyt S| (Geno nn eg mire gach mete graf ee rere ee SENG] tn hn secs can ty pane rorya 2 ea ane nee ‘hes eee (easing myc) and ied essai (casing vasccarsctn) plat aang ago (2a, penepane, xyetzaine) ‘ante vsasn panei wn alerge mnt eaves the aeeconsnsve acho esse nasal congestion, However \aeecansienon ns Astira Educational ebective: Fst generation athntaminos ae nenspc and react wih mtse recaps, nung he scan receptor. Th ads athoinerpie fects fev Fusng. msi, vary reterten, acca, aered etl Sats) Pamacsbay General Principles Ale ints ial Caeves over back an wth sess and as tte on rapoxe and cjcoterzapne. Pas medal sty shale fr modes portent astra, hepattsC and HIV He ast CO count was Sdn. Tho paenhs remote histr of ravenous rg use ut cure) Soest use anil rugs. He ns an aera openin hat causes ash ar ps. Upper gasortesiral ndescopy revels astc miceel ners andersione, ich of hefalaning best lane th pater rer ype? cone BY Met i SOR ae ial aa eyOo ar) - wa aren ‘2.yeavald man comes tne enrpeny depatert aie te ae ote coe pounder and pneaseness. Tae whe 2g0 Ne eves over back an wth sess and as tte on rapoxe and cjcoterzapne. Pas medal sty shale fr modes portent astra, hepattsC and HIV He ast CO count was Sdn. Tho paenhs remote histr of ravenous rg use ut cure) Soest use anil rugs. He ns an aera openin hat causes ash ar ps. 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