PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

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1 Nm: UFI #: PHA 527 Scond Exm Fll 20 On my honor, I hv nihr givn nor rcivd unuhorizd id in doing his ssignmn. Nm Pu ll nswrs on h bubbl sh OAL /200 ps

2 Nm: UFI #: Qusion S I (ru or Fls) (5 poins) ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls Mr whhr h following smns r ru (A) or fls (B). Mr fls if hr is no sufficin informion givn o provid nswr. Incrss nd crss diffrncs should b of clinicl significnc, ohrwis s F. h lipophilic drug A (nihr n cid nor bs) is clrd only by hpic mbolism, crosss mmbrns qui sily, nd dissolvs in h GI rc. Whn givn o Pin A, i hs f u of 0.0, f u of 0.3 nd n inrinsic clrnc of 300 L/h. Pin B shows plsm proin binding of 98 %; h only diffrnc o Pin A.. F h orl biovilbiliy of his drug is highr in Pin B. 2. F h AU of plsm concnrion vs im curv in Pin B fr iv bolus injcion is highr hn whn h sm dos is givn s iv bolus o Pin A. 3. F h AU whn xprssd in fr drug concnrions in plsm will b h sm for boh pins whn h sm dos is givn. 4. F crs in issu binding will ffc h hlf-lif of h drug in boh Pin A nd B. 5. F Incrs in livr blood flow will ffc h hlf-lif of h drug in boh pins. 2

3 Nm: UFI #: Qusion S II (0 poins) 6. onsidr lipophilic unionizd drug, limind only hrough rnl liminion (no civ rnspor). How will dcrs in h frcion unbound in plsm nd chng in crinin clrnc (50% incrs) ffc h iniil concnrion ( 0 ), clrnc (L), AU, nd hlf-lif ( /2 ) whn givn s n iv bolus, biovilbiliy (F) whn givn s bl of low-xrcion drug? (Pls no h mns no cliniclly rlvn chng, nd cliniclly rlvn chngs) A) 0, L, F, AU, /2 B) 0, L, F, AU, /2 ) 0, L, F, AU, /2 ) 0, L, F, AU, /2 E) non of bov combinions. 3

4 Nm: UFI #: Qusion S III (Mching) (20 poins) For h physiologicl chngs lisd blow, slc h inducd chngs on h phrmcoinic prmrs for n minoglycosid (ssum rnl liminion only). Som nswrs my b usd mor hn onc. Howvr, only on nswr pr physiologicl chng. Assum h drug is jus givn onc. Slc h cliniclly rlvn ffc on phrmcoinic prmrs (A) l (B) l () () F (E) nohing hppns or ffc is no lisd Physiologicl chng 7. crs in plsm proin binding 8. Incrs in issu binding 9. Incrs in livr blood flow 0. Incrs in GFR 4

5 Nm: UFI #: Qusion s IV (20poin) A drug, sbl in h GI rc nd in GI mmbrns (f u =0.5, /2 =20 h, no rnspord by rnsporrs), givn orlly, is clrd only hrough rnl clrnc (l rn =0.75 ml/min ;). Afr 5 monhs of rmn, h AU is drmind. I is hlf of wh ws found h nd of monh on. Indic for his siuion, chng in which of h following prmrs xplins his rsul. F chng in GFR 2. F chng in orl biovilbiliy 3. F chng in plsm proin binding 4. F inducion of h P450 sysm 5

6 Nm: UFI #: Qusion S V (20 poins) h following drugs (-5) hv bn givn oxic doss. Wh mhods (A-E) could b usd o r h pin if: 5) rug is limind minly hrough hpic mbolism (high xrcion drug) 6) rug 2 is limind minly hrough hpic mbolism (low xrcion drug) 7) rug 3 is lipophilic (no n cid, no bs) nd limind solly hrough idny. 8) rug 4, lipophilic cid, p = 3, is limind solly hrough h idny. 9) rug 5, Lipophilic cid, p =7.4, is limind solly hrough h idny. Slc for bov drugs h bs singl choic for doxificion from h lis blow: A) Adjus urin ph. B) Incrs urin flow. ) Giv drug h inducs livr nzyms. ) Prform dilysis, s nohing ls will wor. 6

7 Nm: UFI #: Qusion S VI 5 poins) 20. A nw hydrophilic drug is limind hrough rnl nd hpic procsss. Plsm proin binding is 0%. Urin flow is 2 ml. GFR is 20 ml/min. Livr blood flow is 60 L/h. E is 0.26, du o firs pss mbolism in h livr. Wh will b h orl biovilbiliy? You migh hv o round. A) 25 % B) 2.5 % ) 75 % ) 7.5% E) non of h bov Qusion S VII (5 poins) 2. Robr is vry sic nd nds rmn wih n minoglycosid. In ordr o sr him on h minoglycosid you hv o sim Robr s crinin clrnc. Robr is 5 f 0 inchs ll, 64 yrs old, ml, nd wighs 40 g. His srum crinin is.5 mg/dl. Wh is Robr s crinin clrnc? You migh hv o round. A) 70 ml/min B) 80 ml/min ) 900 ml/min ) 0 ml/min E) 20 ml/min 7

8 Nm: UFI #: Qusion S VIII (30 poins) A pin rcivs 400 mg of drug s mulipl iv bolus injcions vry 6 hours. Assum sdy s is chivd. Jus fr h nx dos is dminisrd, blood smpl is n o drmin p (4 mg/l). hn 4 hours lr scond smpl is n (2.8 mg/l). 22. lcul. A) 0.82 (/hr) B) 0.40 (/hr) ).85 (/hr) ) Non of h bov 23) lcul h rough concnrion. A) 2.5 mg/l B) Non of h bov ) 0.25 mg/l ).254 mg/l 24) Wh is h volum of disribuion of his drug. A) 60.5L B) 80.67L ) Non of h bov ) 3.42L 8

9 Nm: UFI #: Qusion S IX (ru or Fls) (5 poins) ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls Mr whhr h following smns r ru (A) or Fls (B) 25. F Assum sdy s hs bn rchd fr hving srd mulipl iv bolus injcions. A sdy s, h vrg sdy s concnrion will dpnd on h volum of disribuion of h drug. 26. F h im o rch sdy s for mulipl iv bolus injcions is ffcd by volum of disribuion of h drug. 27. F h flucuion is ffcd by h clrnc nd volum of disribuion of h drug. 28. F onsidr: u= lnf/. F snds for dgr of firs pss. 29. F onsidr: u= ln( mx / rough )/ o drmin h dosing inrvl for mulipl iv bolus injcion rgimns. Whn his quion is usd for orl forms of dminisrion nd mx is dfind s h uppr nd min is dfind s h lowr concnrion of h hrpuic window, sfy fcor is buil ino h rsuling u. 9

10 Nm: UFI #: Qusion S X (5 poins) ru (A) or Fls (B). On h bubbl sh mr A for ru or B for fls Assum mulipl i.v. bolus dosing rgimn. 30. F For lipophilic drug whos clrnc is consn undr h givn condiions, h following smn cn b md: h srongr h plsm proin binding h lss pronouncd h dgr of ccumulion. 3. F For lipophilic drug whos clrnc is consn undr h givn condiions, h following smn cn b md: h srongr h srongr h issu proin binding h mor pronouncd h flucuion bwn p nd rough concnrion. 32. F For lipophilic, low xrcion drug, clrd minly hrough livr mbolism, h following smn cn b md whn h drug is givn hrough mulipl iv bolus injcions: h srongr h plsm proin binding h highr h vrg sdy s concnrion. 0

11 Nm: UFI #: Qusion S XI (5 poins) 33. Slc h schms h gr wih linr phrmcoinics? A) 5, 9 B) 6, 7, 8 ) 3, 6, 7 ), 3, 4, 6 E), 2, 7, 8

12 Nm: UFI #: Qusion S XII (0 poins) Qusion s I (0 ps): Slc whhr h following smns r ru (A) or Fls (B) concrning n orlly dminisrd drug h is bsorbd by firs ordr procss nd limind by firs ordr procss 34. F h fsr h bsorpion r for givn dos, h rlir h highs concnrion will b obsrvd. 35. F h uni for h bsorpion r will b [/h]. 36. F mx dpnds only on 37. F All h drug hs bn bsorbd whn mx is rchd 38. F For susind rls formulion, clrnc cn b clculd from h rminl slop if V d is nown. 2

13 Symbols Usful Phrmcoinic Equions = dos = dosing inrvl L = clrnc Vd = volum of disribuion = liminion r consn = bsorpion r consn F = frcion bsorbd (biovilbiliy) K 0 = infusion r = durion of infusion = plsm concnrion Gnrl Eliminion r consn ln L Vd 2 ln ln Hlf-lif Vd ln( 2) / L Inrvnous bolus rough (mulipl dos) 0 min Avrg concnrion (sdy s) pss L Orl dminisrion Plsm concnrion (singl dos) F Vd im of mximum concnrion (singl dos) ln mx Plsm concnrion (mulipl dos) F Vd Iniil concnrion 0 Vd Plsm concnrion (singl dos) 0 Plsm concnrion (mulipl dos) 0 P (mulipl dos) 0 mx im of mximum concnrion (mulipl dos) ln mx Avrg concnrion (sdy s) F L lrnc os F l AU l V d Equions/Usful_phrmcoinic_qu_527

14 onsn r infusion Plsm concnrion (during infusion) 0 L Plsm concnrion (sdy s) 0 L lculd clrnc (hiou quion) 2 2 Vd 0 2 L Shor-rm infusion P (singl dos) mx( ) L rough (singl dos) min( ) mx( ) P (mulipl dos) mx L rough (mulipl dos) lculd p mx mx wih mx * = msurd p, msurd im * fr h nd of h infusion lculd rough min min wih min * = msurd rough, msurd im * bfor h sr of h nx infusion lculd volum of disribuion Vd [ mx ( min )] lculd rcommndd dosing inrvl ln mx( dsird ) min( dsird ) lculd rcommndd dos V mx( dsird ) wo-omprmn-body Modl min mx lculd liminion r consn mx ln min wih * mx = msurd p nd * min = msurd rough, msurd ovr h im inrvl b Equions/Usful_phrmcoinic_qu_527 2 AU / b / Vd Vd Vc r rinin lrnc L L cr cr ss ( 40 g) wigh ( ml) 72 p cr ( 40 g) wigh ( fml) 85 p cr Wih wigh in g, g in yrs, crinin plsm conc. in mg/dl nd L cr in ml/min

15 K for minoglycosids K = (rL) Mbolic nd Rnl lrnc E H = lin fub Q l fu H in b l H = E Q = H H QH lin fub Q l fu H in b F H = Q H Q H l in fu b l rn = RBFE = GFR in in ou l rn = l rn = l rn = r of xcrion plsm concnrion R of scrion - R of rbsorpion fu GFR Plsm concnrion Urin flow urin concnrion Plsm concnrion Idl Body Wigh Ml IBW = 50 g g for ch inch ovr 5f in high Fml IBW = 45.5 g g for ch inch ovr 5f in high Obs ABW = IBW + 0.4*(BW-IBW) Volum of isribuion V V P V V P lrnc l os AU l V d V V K P fu fu Equions/Usful_phrmcoinic_qu_527 3

16 For On omprmn Body Modl If h dosing involvs h us of I.V. bolus dminisrion: For singl I.V. bolus dminisrion: 0 V 0 For mulipl I.V. bolus dminisrion: n n( ) V p: = 0; sdy s n rough: = mx ss V ( ) min ss mx ss If h dosing involvs h us of I.V. infusion: For singl shor-rm I.V. infusion: Sinc = for mx mx min V mx ( ) For mulipl shor-rm I.V. infusion sdy s: mx V min mx ( ) Ls modifid 200 :\urrn \ph527_os_op_i\quions\ quions.doc

17 Ls modifid 200 :\urrn \ph527_os_op_i\quions\ quions.doc If h dosing involvs I.V. infusion (mor quions): V (mos gnrl q.) during infusion = so, V (during infusion) sdy s, -, 0 so, L V V pss 0 0 (sdy s) rmmbring 0 nd V L If h dosing involvs orl dminisrion: For singl orl dos: V F ln mx For mulipl orl doss: V F ln mx

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

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