Medicine Exam 1: Practice Questions & Key Equations

E.R., a 48-year-old, 59kg male patient, recieced a living-related renal transplant many years ago. He is currently receiving Sandimmune 300 mg PO as the solutionBID and, in addition, prednisone 5 mg/day and mycophenolate 1,000 mg BID.E.R.'s current serum creatinine is 2.1 mg/dL, and his steady-state cyclosporine trough concentration is 590 mcg/L. The physician has ruled out the possibility of rejection and believes that the recent rise in serum creatinine is because of cyclosporine toxicity.What questions would one ask E.R., and how would one adjust his cyclosporine regimen to achieve a new steady-state cyclosporine concentration of approximately200 mcg/L?

100

BT is a 50-year-old, 75-kg (height = 5 ft 10 in) male renal transplant patient. The patient's liver function tests are normal, and the patient is taking Sirolimus. The mean sirolimus Cl/F for adult renal transplant patients taking Sirolimus is 240 mL/h/kg and the mean V/F is 10 L/kg.What is the oral loading dose in milligrams for sirolimus designed to achieve a steady-state sirolimus trough blood concentration equal to 5ng/mL?

3.75

DT is a 48-year-old, 85-kg (height = 5 ft 10 in) male renal transplant patient. The patient's liver function tests are normal, and the patient is taking Sirolimus. The mean sirolimus Cl/F for adult renal transplant patients taking Sirolimus is 240 mL/h/kg and the mean V/F is 10 L/kg.The dosing interval is 24 hours.What is the initial oral maintenance dose in milligrams for sirolimus designed to achieve a steady-state sirolimus trough blood concentration equal to 6 ng/mL?

3

HO is a 50-year-old, 75-kg (height = 5 ft 10 in) malerenal transplant patient 2 days posttransplantsurgery. The patient's liver function tests are normal.The clearance of the patient is 6mL/min/kg. Thedosing interval is 12 hours.What is an initial oral cyclosporine dose designed toachieve a steady-state cyclosporine trough bloodconcentration equal to 250 ng/mL.?

300

HO is a 50-year-old, 75-kg (height = 5 ft 10 in) male renal transplantpatient 2 days posttransplant surgery. The patient's liver functiontests are normal. The mean tacrolimus clearance for adult patients is0.06 L/h/kg. A 12-hour dosage interval will be used for this patient.The average bioavailability is 25%.What is an initial oral tacrolimus dose in milligrams designed toachieve a steady-state tacrolimus trough blood concentration equal to 15 ng/mL?

3

C.F. continues to improve clinically 4 days after the liver transplant. He is currently taking tacrolimus 6 mg PO BID. Trough tacrolimus concentrations have been obtained serially daily in the morning (day 2: 8 mcg/L; day 3: 10mcg/L; and day 4: 12 mcg/L).The transplant physician would like the patient to have a higher therapeutic target of tacrolimus because he has increased risk of organ rejection in this immediate posttransplant period. The team would like you to adjust the tacrolimus dose to achieve a trough concentration of 18 mcg/L. What is the desired daily dose?

18

HO is a 50-year-old, 70-kg (height = 5 ft 10 in) male renal transplantpatient. The patient's liver function tests are normal, and the patient istaking Sirolimus. The mean sirolimus Cl/F for adult renal transplantpatients taking Sirolimus is 240 mL/h/kg and the mean V/F is 10 L/kg. What is the initial oral maintenance dose for sirolimus designed toachieve a steady-state sirolimus trough blood concentration equal to 5ng/mL?

4

C.G. was taking a stable regimen of cyclosporine modified 200 mgPO BID, sirolimus 2 mg PO daily, and prednisone 10 mg PO daily.Her steady-state cyclosporine concentration was 200 mcg/L (viaHPLC assay) and steady-state sirolimus concentration was 9mcg/L on this regimen. C.G. was started on fluconazole 200 mg PO daily to treat a fungal infection. Two weeks later, her plateletcount decreased from 200K to 75K, and her white blood cells decreased from 7K to 2.5K. Her latest cyclosporine blood concentration was 470 mcg/L, and sirolimus concentration was 22mcg/L. What could account for her thrombocytopenia and leukopenia and elevated cyclosporine and sirolimus concentrations? How would you manage this interaction?

The choice is to either discontinue the fluconazole and substitute for another drug or decrease the dose of sirolimus.

Immunosuppressants are vital in preventing and treating allograft rejection in the transplant patient. Which of the following statements is true?

A. Immunosuppressants have a wide therapeutic window
B. Immunosuppressant drug therapy is NOT individualized
C. Subtherapeutic concentrations can lead to toxicity and adverse effects
D. Supratherapeutic concentrations can lead to toxicity and adverseeffects

D

Sandimmune® (cyclosporine), the Original formulation of cyclosporine, and Neoral® (cyclosporine modified) are bioequivalent. (Select the correct response)

True
False

False

Sirolimus is an immunosuppressant drug. Which of the following plasma proteins does Sirolimus mainly bind to?
A. Albumin
B. Alpha glycoprotein
C. Lipoprotein
D. Glycoprotein coupled receptor

A

The hepatic metabolism of Tacrolimus is mainly through(____________).
A. CYP1A1
B. CYP3A5
C. CYP3A4
D. CYP2C19

C

A patient receives an intravenous dose of 2000 mg.What is the plasma drug concentration in mg/L if thevolume of distribution is 28.6 L?

70

A patient receives an intravenous dose of 2000 mcg.What is the volume of distribution in Liters if the plasma concentration is 24 ng/mL?

24

A 4 mcg/kg dose of an investigational drug is ordered for a patient.The patient weighs 110 pounds. Following the intravenous bolus administration of the drug, plasma levels were measured. The extrapolated concentration at time zero was determined to be 0.429mcg/L. Calculate the volume of distribution ( in liters) for the investigational drug

466

A 5 mcg/kg dose of an investigational drug is ordered for a patient.The patient weighs 180 pounds. Following the intravenous bolusadministration of the drug, plasma levels were measured. Theextrapolated concentration at time zero was determined to be 10mcg/L. Calculate the volume of distribution ( in liters) for theinvestigational drug

41

A dose of 500 mg of a drug X is administered to a patient, and the following concentrations results at the indicated times below. Round the result to the nearest tenth. What is an estimate of the half-life in hours of drug X? (Rounds to the nearest tenth)

2.3

What is the Half-Life in HoursAssociated With First-Order Drug Elimination' Fora starting concentration of 60 mg/L, and if k = 0.1hr-1?

7

What is the renal clearance in liter per hour if the renal rate constant of elimination ke=0.12 hr-1 and the volume of distribution is 65L?

8

What is the renal clearance in liter per hour if the renal rate constant of elimination ke=0.2 hr-1 and the volume of distribution is 40L?

8

A drug is administered intravenously as a 500 mg dose. The AUC is 102 mgxhr/L. The oral bioavailability is 35%. What is the clearance of the drug in L/hr?

5

A drug is administered intravenously as a 400 mg dose. The AUC is 85 mgxhr/L. The oral bioavailability is 25%. What is the clearance of the drug in L/hr?

6

An drug is administered P.O. as a 500 mg dose. The AUC is 100 mgxhr/L. The oral bioavailability is 55%. What is the clearance of the drug in L/hr?

2.8

An drug is administered P.O. as a 400 mg dose. TheAUC is 85 mgxhr/L. The oral bioavailability is 25%.What is the clearance of the drug in L/hr?

1.2

What is the volume of distribution of Cyclosporine if the clearance is 27 L/h and the half-life is 12h?

468

What is the volume of distribution of Cyclosporine if theclearance is 27 L/h and the half-life is 10h?

390

A patient weighs 180 lbs. What is the volume of distribution inLiter of Cyclosporine if the population estimate of the volume of distribution is 5L/kg?

409

HO is a 50-year-old, 75-kg (height = 5 ft 10 in) male renal transplant patient 2days posttransplant surgery. The patient's liver function tests are normal. The desired steady-state cyclosporine trough blood concentration equal to 250ng/mL. The clearance of the patient is 6 mL/min/kg. The dosing interval is 12hours.What is the drug clearance in L/hr according to disease states and conditions present in the patient?

27

HO is a 50-year-old, 75-kg (height = 5 ft 10 in) male renal transplant patient 2 days posttransplant surgery. The patient's liver function testsare normal. The mean tacrolimus clearance for adult patients is 0.06L/h/kgWhat is the Estimate clearance (L/h) according to disease states and conditions present in the patient?

4.5

The mean sirolimus Cl/F for adult renal transplant patients taking Sirolimus is 240 mL/h/kg. What is the clearance in L/h if the patient weighs 70 Kg?

17