{[ promptMessage ]}

Bookmark it

{[ promptMessage ]}

Pceut532_Final_2006 - Student l(4 pts Assuming a VmaxN and...

Info iconThis preview shows pages 1–7. Sign up to view the full content.

View Full Document Right Arrow Icon
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Background image of page 2
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Background image of page 4
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Background image of page 6
Background image of page 7
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Student # l. (4 pts) Assuming a VmaxN and Km of phenytoin of 500 mg/d, 50L and 4 mg/L respectively, calculate the half-life of phenytoin at a plasma concentration of 0.1 mg/L. State your assumptions ’ in arriving at your answer. or , , 5 << kin , Sm Pawn/«r; (AME/AR “lMI‘al‘uS' L p. lHEmf—me, £72,: 9.53131: 49L CL. = Virus}, K,“ Cb: SOOwS ”Eli’- TUS'LXLEILWWL/ Lila? ‘ D L‘lmm w: T. r ; a WW, 4777/: O 6% V W Qifimfigf ’"l4 (2:) was Ullijl' 5;. MW M CL g wa 2. (16 pts; 4 pts each) Check the appropriate answer A. A drug will demonstrate Michaelis—Menten pharmacokinetics when its major route of elimination (by metabolism or transport) is saturable. ’ True % False B. The higher the Km of a drug for an enzyme or a transporter, the greater its affinity for the enzyme or transporter True___ False g C. The plasma steady—state concentration of a drug demonstrating Michaelis—Menten kinetics Will increase disproportionately with an increase in infusion rate of the drug True , Z" False D. The half—life of a drug demonstrating LINEAR pharmacokinetics is independent of the dose while that of a drug demonstrating NONLINEAR pharmacokinetics is dependent on the dose True 3 1 False 3. SV is a 15-year-old 60—kg female With a history of generalized tonic—clonic seizures who presents to the emergency room with a generalized seizure. Her initial seizure is treated with lorazepam. The medical record for SV documents that she is currently taking Dilantin® (Sodium Phenytoin) 300 rug/day; however SV admits to not taking her medication regularly. Her total phenytoin plasma concentration in the ER is found to be 1 ug/ml. Her albumin is in the normal range. Phenytoin “facts”: F = 0.9, Salt form’of Na+ Phenytoin = 0.92 Therapeutic range: Total phenytoin: 10 f 20 rig/ml Unbound phenytoin: 1—2 rig/ml A. (5 pts) You are asked to calculate an intravenous loading dose for SV to achieve a target concentration of 18 rig/ml. V m; 6 Q ”C, 6;, LU; .4 H ) w; V (c as (m m (w raw/i m mm B. (5 pts) If you decide to administer the same loading dose as an oral dose, describe how you would administer it and explain why. u . ‘1 "E if?“ 'lwa 005C; wwon tame. We 33:2. \Ucmeasfio ”to 31"?) 3 $0?) W3 Ma éh MM Opt gemvsfl C)? we“ lgxoboemefiwfi? gamma": {fish “MEN WE it ‘tht‘, 005$. wnoug Maufi; “m 75%?“ Sfihfi rm 1m BKWES M' W90 W3 Em gfitmse aw §m~masmwls «tnwni‘itwb W Mmfimwln F C. (5 pts) LH is a 80-year—old 85—kg male with a history of complex partial seizures. He arrives , in your clinic with nystamus and ataxia. Admitting labs including a positive ethanol level, albumin plasma concentration of 2.5 gm/dl and a total phenytoin plasma concentration of 15 rig/ml. You are asked to rule out ethanol vs. phenytoin intoxication. I . r a.) win. H Mammal if Low. WHHAA Mam») WS «yam. 9H! CoN‘rr-“Timm - l5 ’" w' -” ‘ A? d, . N951. M15; [UbT moggsmtmwf \ZEFLCéc/T' Hts TRfiMQEmLL/l ("25:13.5 wife ”leak... g5 . gag” W 9%“) (Saga, am" cove, we, mm Caucaswg rs. ”eJaErwt/ztric pm; $1“:— ; 15$: , ‘ um ’(bd M 20 it» 0 145 E 3 $.13; (1~§am\) MM :5 PH‘ 4” (2 I’W‘W l Ab ~ ”fin“. ....... “www— -—7 {aw-M’— m3 Parry,» (3%? l5 0":ij gum/WW OUT of: Kama”, IO’ZOW.‘ ] at; Him!) we Sm»?! u: ms WT” 0a.. fimamb . But 2, We race-.233 Emulate ceases tom “realms? , 4. Fill in the blanks: (10 pts total; 2 pts each) A. 3a a"l ;% . is a metabolic enzyme in which females have significantly greater activity than males While US“: lift} is a metabolic enzyme in which males have significantly greater activity than females. B. Decreased renal clearance and increased bioavailability due to decreased activity of , in females compared to males maybe responsible for the increased risk of mortality 1n females compared to males receiving digoxin for treatment of congestive heart failure. C. The increased . ,Q 96% (A... for a loss of efficacy. of lithium during pregnancy could be responsible D. Chronic liver cirrhosis results in a decrease in the metabolism of drugs catalyzed by all CY P450 isozymes except for 1% 5. Fill in the blanks With either increase (1‘), decrease (l) or the same or no change (<->). (15 pts total, 1 pt each) A Compared to adult levels, albumin plasma concentrations are d/ in neonates, t“? in a 5 year old child and =3 in the elderly. r 7’ B. Compared to adult levels, the unbound clearance of a drug that is metabolized predominately by glucuronide conjugation» pathways (ml/min/kg) is i in neonates, g) in a 5 year old child and i; in the elderly. C. Compared to adult levels, the clearance of a drug eliminated predominately by renal clearance is J; in neonates, H in a 5 year old child and d/ in the elderly. ‘ D. A combination of a d/ in albumin concentrations and a i _ in CY P2C9 dependent metabolism of phenytoin during pregnancy results in a \lr total phenytoin concentrations and a \J/ in unbound phenytoin concentrations. The change in total phenytoin concentrations is ’i‘ than the change in the unbound phenytoin concentrations. 13.0 The effect of acute hepatitis on CYP3A4 dependent metabolism is 4/ compared to the effect of chronic liver cirrhosis. 6. (4 pts) Morphine is extensively metabolized by the liver to morphine 3—glucuronide and morphine 6—g1ucuronide. Explain Why doses of morphine need to adjusted in patients with renal disease. EfiWL (Ag—gl/chg Qasfiowmcci. Fore Ectmxuamd (.7 Prawn“ MEW-Afififiu’flfufr. rag”: Um r, ,mfiu 1mg” MMQWWE. fv’lfl‘lmficwflt‘as cum, peasant” ago arming; I . 9* Phonon/(mil) (9910!!) fifwficfiw 7. Given the following equation for the clearance of vancomycin, answer the following question. ”an Cl (ml/min) = (0.695 * (CrCl) + 0.05)* weight (kg) KW g @FQ. o’i’fi’l‘wg, A. (3 pts) Vancomycin is predominately eliminated unchanged by the kidneys and the clearance is correlated with a patient creatinine clearance as described above. 1) What does the 0.05 represent in the equation describing the clearance of vancomycin? Biwubfiswj garaAEANLE, (in-tawny , 2) How significant is this for a male patient with normal renal function (CrCl = 120 ml/min). 0 d3? t5 taillight “flag Con-{3 aafig ”to («fig , r110 Mb/MM- NR“ kfifv‘t mm amw‘h 3) Is it significant for a male patient with renal failure (CrCl 20 ml/min)? ‘(f . Us Ewfiw "w «am; has; it” WWVD Renew/“i (5%“! his: “metal OP 1:31!)er CL, ,2 NUT SigNtPu/AMT. B. (3 pts) If a patient arrives in the ICU in a new onset acute renal failure and you estimate his CrCl using his weight, age and serum creatinine using the Cockcroft—Gault equation. Would your CrCl estimate be correct, too high or too low. Why? r Memo fit as.) mgagthA-mm @amusva. 1r wanes. T‘iMfi, file. flaunt, (Axevflfi, “m snow-k? nu Smom Lanawtwmfi i8 Ham‘s" linux11; 1W ix We“ \1 {ZCWC («QWUGA Tums E.Qvumovj . (4 pts) A. List tw_o disease states where albumin concentrations would be expected to be decreased. Q, (041351 5 Mncuv‘tm 110'“) B. List two disease states where you would expect increased concentrations ofor “fa—Cid glycoprotein? 52mm, ONE/ASE” @cmfi, M3; . Fill in the Blanks or circle the correct answer. (1 pt each, 14 pts total) A. The incidence of the slow acetylator phenotype (NATZ) in the Asian population is “725’ Z. and the incidence in the Caucasians and African~American population is § 0 7- . B. The incidence of the poor metabolizer phenotype of CY P2D6 1n the Caucasian population 1s Q “0 7’ and 1n the Asian population it is 4 1 7° . C. The incidence of the poor metabolizer phenotype of CY P2C19 1n the Caucasian and African— American population is 2’ 5 7“ and 1n the Asian population it is ’7’ ”‘9 D. The average steady state concentrations after oral administration of hydralyzine in a slow acetylator of NAT2 are @, lower, the same) compared to a fast acetylator. After intravenous administration, the average steady state concentrations are (higher, lower, the same in a slow acetylator compared to a fast acetylator. E. 0 M‘El’myb’i’ is a commonly used drug metabolized by CY P2C19 with dose dependent efficacy that is significantly greater in poor metabolizers than in extensive metabolizers? F. LS had been receiving metoprolol (CYP2D6) for the treatment of his blood pressure. His clinician added fluoxetine, a CY P2136 inhibitor. If you knew that LS was a poor metabolizer of CY P2D6, what d you expect his plasma concentrations of metaprolol to do? (Increase, decrease or remain the s e) G. 0 63mm WW5; is a probe used for phenotyping CY P2D6 and Lamina. is used as a probe to phenotype NATZ. V H. Cayman: us is the ethnic group with the highest incidence of low and reduced activity alleles of CY P2C9? I. l/V We) is a commonly used substrate of CY P2C9 Whose efficacy has been shown to be dependent on gene—dosing. 10. (5 pts) Procainamide causes SLE in NATZ slow acetylators. Explain Why reducing the dose in slow acetylators can decrease the incidence of toxicity comparable to the incidence found in fast acetylators. Use equations to demonstrate. ‘ ~Sl4‘3 \3 nausea $3,»; is ”ream, Mafifimomr‘fiw Qt: Metzmmmee, MM L ~ N s cow {An/5m; swarm? B CLL n5” Dacefiama‘ 1m. , u+ Ck; F .0 MW; E“ t“ W? {Wis . gyzrvzfrz’fg d I: i6 h am e ‘ ifet‘hr * is” it “E“ mi, T ”fir” iCL'wMe ”We; DfigLE/ASE- “Q 1%, NATL Onsuwmxb cinemas D; fiaegea w - ' , . pm. . be: '7 a r; 30" 1'5" a} 1K pwmmom all“ “we; ens: beam Mi. fines M um mews mm W“ *‘i‘ . b r 9" if ’ ZEQUQNM “WE.”- GOJSNE,’ ”i“: awed-inf FOR ”ME. Oétfifié‘bfir We) _ _ 59g Mefi‘tfiw 0’3 {Lbfi spanimkfiiw 1,) we QQEWW“ Wedgie» gwtm P" G F W To a we mew a» we“; be fl/Mfw "’ , 11. (4 pts) Using the concept of gene— —dosing, complete the graph of concentration vs. time that you would expect to find in 4 people who have received a single IV dose of a drug significantly metabolized by CY P2D6 and are either 1) a homozygous poor metabolizer PM 2) a heterozygous extensive metabolizer 1 P" 3) a homozygous extensive metabolizer EM 4) an ultrametabolizer of CYP2D6. U M l/CWa Concentration o F 12. (3 pts) A lactating mother is prescribed cephalexin for a urinary tract infection. She wants to know whether or not her 2—month—old son Will have measurable levels of Cephalexin if she takes the drug while breastfeeding. Cephaiexin is 20 % bound to plasma proteins. What can you tell her? EEQAUME. Qémgags\d rs {2,0 59 lawn/r: “so gamma {Esagsgwfi (a: 0-?) \4— l5 Gamma, was" awe, fees. fimmwvx) Cb“ Cm“ ”J“ ”MW“ 1“ 1 s (MAC) 1 («Ma r15 (NJ? "to (owners/ea, we; Mafiwm Mammy“ or??? i ,v» i aa a! -. if ' a" {fig-Q? M first, fisr‘am {3s ‘3‘ r. it; 5*:- a}; as; as shad; k ‘3' “L503 are 655% «5‘4 Masha gamaaen. {WMQMCK‘V {£5 sf «:3st twigs Z ...
View Full Document

{[ snackBarMessage ]}