PHA Final Exam Fall 2007

Transcription

1 PHA 5127 Final Exam Fall 2007 On my honor, I hav nithr givn nor rcivd unauthorizd aid in doing this assignmnt. Nam Plas transfr th answrs onto th bubbl sht. Th qustion numbr rfrs to th numbr on th bubbl sht. Plas fill in all th information ncssary to idntify yourslf. Th proctors will also collct your xams. GOOD LUCK. 1

2 Qustion 1: Slct th corrct statmnt(s) concrning a two-compartmnt body modl. (5pts) 1. For a two-compartmnt-body modl drug, th rat constant dscribing th limination of th drug from th cntral compartmnt (K10, quantifying urinary and/or mtabolic limination) is largr numbr than bta, 2. Th bi-xponntial concntration tim-profil, is du to th fact that K10 changs ovr tim. 3. Vd ss is smallr than VD c 4. Lt us assum that th toxicity of aminoglycosids is rlatd to th drug-concntration in a dp priphral compartmnt into which th drug ntrs and lavs vry slowly. Drug toxicity will b obsrvd immdiatly aftr an iv bolus of this aminoglycosid. Th corrct statmnt(s) is (ar): A: 1 B: 2 and 3 C: 1 and 4 D: 1 and 3 E: 1, 2 and 3 2

3 Qustion 2: Slct from th following statmnts th corrct statmnt(s) (5pts) 1. For a sustaind rlas formulation (drug shows flip-flop kintics), th tim to rach stady stat dpnds on th rat of rlas. 2. Th tim to rach stady stat is dtrmind by th half-lif of th drug. 3. Th tim to rach stady stat is affctd by claranc and volum of distribution. 4. Tim to rach stady stat dpnds on th dosing intrval. A: (1, 2, 3, 4) B: (1, 2, 4) C: (1, 3) D: (1, 2, 3) E: (2, 3) 3

4 Qustion 3-7: Th following applis to qustions 3-7: Nam: A 60-kg patint is to b startd on a continuous intravnous infusion. To achiv an immdiat ffct, a loading dos is administrd ovr 30 min. (givn as short trm infusion ovr 30 min). Th continuous infusion is startd immdiatly aftr th loading dos. From a prvious rgimn of th sam drug, th patint s k is 0.07 h -1 and th V d is 40 L. Assum that non of this drug has bn administrd bforhand. Qustion 3: In ordr to achiv a Cp ss of 7.5 mg/l, what would b th loading dos (mg) givn ovr 30 min? (5pts) A B C D E 300 mg 305 mg 600 mg 610 mg non of th abov In this qustion w want our concntration at th nd of a 30 min infusion to b 7.5 mg/l. It is statd that this is th first dos so w can us th Cmax quation for a singl dos. Th purpos of a loading dos is to rach th dsird concntration quickly. Cl=k *V d =0.07hr -1 *40L=2.8L/hr Cmax=Dos/Cl*T*(1- -k*t ) whr T=infusion tim Dos=Cmax*Cl*T/(1- -k*t ) Dos=7.5mg/L*2.8L/hr*0.5 hr/( *0.5 )=305.23mg ~305mg 4

5 A 60-kg patint is to b startd on a continuous intravnous infusion. To achiv an immdiat ffct, a loading dos is administrd ovr 30 min. (givn as short trm infusion ovr 30 min). Th continuous infusion is startd immdiatly aftr th loading dos. From a prvious rgimn of th sam drug, th patint s k is 0.07 h -1 and th V d is 40 L. Assum that non of this drug has bn administrd bforhand. Qustion 4: In ordr to achiv a Cp ss of 7.5 mg/l, what will b th rat of th continuous infusion? (k o for th following constant rat infusion) (5pts) A: 2.1 hr -1 B: 21 mg/ 0.5 hours C: 21 mg/hr D: 21 mg E: non of th abov Th ky to this qustion is to watch your units. From th quation sht Cp ss =k o /Cl k o = Cp ss *Cl=7.5mg/L*2.8L/hr=21 mg/hr You can s that th L cancls out. 5

6 A 60-kg patint is to b startd on a continuous intravnous infusion. To achiv an immdiat ffct, a loading dos is administrd ovr 30 min. (givn as short trm infusion ovr 30 min). Th continuous infusion is startd immdiatly aftr th loading dos. From a prvious rgimn of th sam drug, th patint s k is 0.07 h -1 and th V d is 40 L. Assum that non of this drug has bn administrd bforhand. Qustion 5: What will b th plasma concntration 12 hours aftr th continuous infusion was startd? [Rmmbr a loading dos infusion was givn, s qustion 3] (5pts) A: 4.5 mg/l B : 6.5 mg/l C: 7.5 mg/l D: 15 mg/l E: Non of th abov. Du to th fact a loading dos was administrd and w calculatd th loading dos and infusion rat to rmain at 7.5 mg/l in this patint, this will b th concntration until th infusion is stoppd dspit how long th constant infusion continus. 6

7 A 60-kg patint is to b startd on a continuous intravnous infusion. To achiv an immdiat ffct, a loading dos is administrd ovr 30 min. (givn as short trm infusion ovr 30 min). Th continuous infusion is startd immdiatly aftr th loading dos. From a prvious rgimn of th sam drug, th patint s k is 0.07 h -1 and th V d is 40 L. Assum that non of this drug has bn administrd bforhand. Qustion 6: If th continuous infusion is stoppd aftr 3 days, what will b th plasma concntration 12 hours aftr th stop of th infusion? Plas prform calculations, w will chck. (5 points) A 0.6 mg/l B: 3.25 mg/l C: 3.75 mg/l D: 6.0 mg/l E: Non of th abov Answr: B At stady-stat, C pss = 7.5 mg/l. Aftr stop of th infusion: drug follows on-compartmntal modl with first-ordr limination: C p(t ) =C pss * (-k*t ) C p(12hr) = 7.5 mg/l * (-0.07 hr-1*12 hr) = 3.24 (mg/l) 7

8 A 60-kg patint is to b startd on a continuous intravnous infusion. To achiv an immdiat ffct, a loading dos is administrd ovr 30 min. (givn as short trm infusion ovr 30 min). Th continuous infusion is startd immdiatly aftr th loading dos. From a prvious rgimn of th sam drug, th patint s k is 0.07 h -1 and th V d is 40 L. Assum that non of this drug has bn administrd bforhand. Qustion 7: Th infusion is continud for 3 days and th stady stat concntration has bn maintaind at 7.5 mg/l. This infusion is stoppd bcaus th physician wants to incras th stady stat concntration to 15 mg/l. What will b th nw infusion rat? Plas prform calculations, w might chck. (5 points) A: 21 mg/l B: 42 mg/0.5 h C: 21 mg/0.5 h D: 21 mg/h E: Non of th abov. Answr: C C pss =K0/CL K0=C pss *CL K0=15 mg/l * 0.07h -1 * 40 L = 42 mg/hr = 21 mg/0.5hr 8

9 Th following prtains to Qustions 8-9 A 60 kg patint is startd on 80 mg of Drug A, vry 6 hr givn as a on-hour infusion. Qustion 8: If this patint is assumd to hav an avrag volum of distribution (valu of th population man) of 0.25 L/kg and a normal half lif of 3 hr. What will b th C max at stady stat? Plas provid calculations. (5 points) A: 6.3 mg/l B: 8.9 mg/l C: 12.2 mg/l D: 4.8 mg/l E: Non of th abov Answr: A Vd=0.25 L/kg*60 kg= 15 L K=ln2/t 1/2 =0.693/3hr=0.231 (hr -1 ) CL=Vd*k=15L * hr -1 =3.465 (L/hr) C max = 80 mg/3.465l/hr/1hr*(1- (-0.231hr-1*1hr) )/(1- (-0.231hr-1*6hr) ) =6.35 mg/l 9

10 Th following prtains to Qustions 8-9 A 60 kg patint is startd on 80 mg of gntamycin, vry 6 hr givn as a onhour infusion. Qustion 9: Basd on th abov volum of distribution and t 1/2 stimats, is th 6 hr dosing intrval sufficint to achiv a fluctuation of at last 6? Plas provid calculations. (5 points) A: ys B: no C: Don t hav nough information to mak this conclusion. Answr: B K=ln2/t 1/2 =0.693/3hr=0.231 (hr -1 ) Fluctuation=C max /C min =1/ (-k*(tau-t) =1/ (-0.231*(6-1)) =3.17<<6 10

11 Qustions Th following qustions ar rlatd to th quation shown blow. Explain th maning of th blockd parts of th quation in th following qustions Cp min = ko CL 1 1 k k T τ k ( τ T) Qustion 10: What information dos k o /CL provid (5 points) k o Cl A: C max aftr th first dos whn givn as iv infusion ovr th infusion tim T. B: Trough concntration at stady stat whn givn as infusion. C: C max aftr th first dos whn givn as iv bolus injction. D: Dgr of accumulation. E: Concntration obsrvd at stady stat whn first infusion would nvr stop. Answr: E A: B: 11

12 Qustion 11: What dos this part of th quation tlls us (5 points) 1 1 k τ A: Quantifis to what dgr stady stat has bn achivd for th first constant rat infusion with T bing th infusion tim of a short trm infusion. B: Dgr of accumulation obsrvd at stady stat whn th drug is givn as short trm infusion with an infusion tim T and a dosing intrval tau. C: C max aftr th first dos whn givn as short-trm infusion. D: Allows th calculation of th trough concntration, without this part of th quation, on would obtain th tru C max. E: Non of th abov. Solution: B 1 1 k τ is accumulation factor 12

13 Qustion 12: What dos this part of th quation allows us to calculat (5 points) k ( τ T) A: C max aftr th first dos whn givn as an short-trm iv infusion B: Allows calculation of Trough concntration at stady stat from pak lvls aftr multipl short-trm infusions. C: C max obsrvd som tim aftr th stop of th infusion (th nurss C max, th on that will b snd to th lab) D: Dgr of accumulation E: Non of th abov Solution: B t' = τ T is th tim from pak to trough concntration C = C trough pak k ( τ T) 13

14 Qustion 13: For a lipophilic, protin bound, low xtraction drug clard by livr and kidny, slct th corrct answr(s) (5 points) 1: Incras in th livr blood flow will incras its claranc. 2: Livr nzym inducrs will incras its oral bioavailability 3: Incras in plasma protin binding will dcras its volum of distribution (assuming f ut is th sam) 4: Dcras in cratinin claranc will dcras its intrinsic claranc 5: Dcras in plasma protin binding will incras its oral bioavailability Slct th corrct statmnt(s): A: 1, 2, 3, 4 B: 1, 3 C: 3 D: 1, 2, 3, 5 E 3, 5 Solution: C for low of xtraction drug: Q f Cl = 1 is wrong H u int Cl fu Clint QH + fu Clint F 1 2 and 5 ar wrong only C rmaind also cratinin claranc will not affct hpatic intrinsic claranc 4 is wrong f 1 f =V + 3 is corrct u b Vd=V p + V p V V f T ut f T ut f T ut 14

15 Qustion 14 (15 points) A 50 yar-old mal is admittd to th hospital with a gram-ngativ abdominal infction. This patint is to b startd on gntamicin givn as a half-hour infusion. Th patint wighs 72 kg and is 5 8. Th srum cratinin for this patint is 1.1 mg/dl. Th stady stat pak concntration should b 10 mg/l with a trough of 1.5 mg/l. Dsign a dosing rgimn basd on population pharmacokintics. Claranc quals cratinin claranc Vd=0.25 BW. For Vd us ABW if th patint is obs. Do not us th k quation for aminoglycosids. A. 120 mg TID B 180 mg QD C. 180 mg TID D. 130 mg BID E. non of th abov IBW = = 68.4kg TBW = 72kg < 120% IBW, not ob (140 50) 72 Cl = CrCl = = 81.8 ml / min = 4.9 L / h Vd = = 18L K = Cl / Vd = 0.27/ h τ = ln(10 /1.5) / 0.27 = 7.04hr 8hr TID k τ (1 ) D= Cmax Cl T = 170mg k T (1 ) C is corrct (E is OK only if your calculation is right) 15

16 Qustion 15: (5 points). Drug-K follows a linar on-compartmntal modl. Which profil will rprsnt Drug-K with 1-hr IV infusion in th following graph? Slct th corrct graph. A. B. C. D. E. Solution: A 1-hr IV infusion C =C pak 1h linar on-compartmntal modl a straight lin aftr on hr in th smi-log plot 16

17 Qustion16: (5 pts) Th sam dos of Alprazolam was givn ithr alon or with carbamazpin. Explain what is going on by slcting th corrct answr from th following list. 1: Th claranc of alprazalam is incrasd in th prsnc of carbamazpin. 2: Alprazalam is likly to b a low xtraction drug. 3: Carbamazpin is an nzym inhibitor. 4: Carbamazpin dcrass livr blood flow. Th corrct answr(s) is(ar): A: 1 B: 1, 2 C: 3, 4 D: 2, 3 E: 1, 2, 4 17

18 Answr: 1) Th claranc of alprazalam is incrasd in th prsnc of carbamazpin. Tru. Th alprazolam concntration dcrass fastr in th prsnc of carbamazpin fastr claranc 2) Alprazalam is likly to b a low xtraction drug. Tru. Th hpatic claranc of a low-xtraction drug is dpndnt on th fraction unbound in plasma and intrinsic claranc. If an incras in th intrinsic claranc has a significant ffct on th ovrall claranc, th drug is likly to b a low xtraction drug. 3) Carbamazpin is an nzym inhibitor. Fals. Th alprazolam concntration dcrass fastr compard to th control nzym induction. 4) Carbamazpin dcrass livr blood flow. Fals. Thr is no indication that it would do that. Qustions Mark whthr th following statmnts ar tru (A) or fals (B). Qustion 17 (5 points) T (A) F (B) Loading doss ar mainly givn for drugs with high k valus Answr: In gnral, loading doss ar givn to achiv stady-stat conditions right away. This bcoms spcially important for drugs with long half-livs (sinc it would tak othrwis vry long to rach stady-stat) and consquntly small k valus. 18

19 Qustion 18 (5 points) T (A) F (B) A larg volum of distribution during th limination phas of a two-compartmnt body modl might b du to th high mtabolic claranc of this drug. Answr: amout of drug in th body V d = plasma concntration Th volum of distribution rlats th amount of drug in th body to th rspctiv plasma concntration. If a drug is clard vry fast from th cntral compartmnt, it might tak som tim for th drug to com out of th tissu. Th actual amount of drug in th body is still high whras th plasma concntration is low high volum of distribution. Qustion 19 (5 points) T (A) F (B) Linar pharmacokintics mans that th plasma drug concntration vrsus tim plots will rsult in a straight lin. Answr: Linar pharmacokintics is dfind by a linar rlationship btwn dos and AUC. Dpnding on th administration rout, numbr of compartmnts and limination kintics, th concntration-tim profil can show a linar rlationship. 19

20 Qustion 20 (5 points) T (A) F (B) Th dosing intrval for multipl short trm infusions is Answr: dtrmind by th dsird fluctuation, th half-lif of th drug and th tim ovr which th infusion is givn. τ = C ln C max(dsird) min(dsird) k + T τ : T : C F = C t = 1/2 Dosing intrval Infusion tim max min ln2 k ( SS) ( SS) 20

21 Qustion 21 (2 points) (Bonus Qustion) I likd th nw half-smstr format. Plas slct th statmnt that bst dscribs your opinion. All answrs will b awardd 2 points. A: I strongly agr B: I agr C: I don t car, ithr way is fin D: I disagr. I somwhat prfr th old format. E: I strongly disagr, I did not lik it at all 21