Pharmacokinetics

Question 0

Mass spectrometry

Answer 0

Gold standard of chromatography

Question 1

Narrow therapeutic drugs

Answer 1

CD FLP ST VW

Question 2

PK info

Answer 2

Prescribing information

Clinical pharmacology of package insert

Question 3

Goal of TDM

Answer 3

Better relationship between Cp and response than dose and response

Goal: optimize patients clinical outcomes by managing their medication regimen with measured drug concentrations

Question 4

Pharmacodynamic markers

Answer 4

BP, cholesterol, coagulation time

Question 5

High performance liquid chromatography

Answer 5

Lipophilic, stationary, long retention time

Hydrophilic, mobile, short retention time

Question 6

Robustness

Answer 6

Rapid turnaround time

Question 7

Specificity

Answer 7

Lack cross reactivity

Question 8

Sensitivity

Answer 8

Detection of units nanograms

Question 9

Concentration interpretation

Answer 9

Interpret after considering

Clinical response
Demographic and clinical status
Dosage regimen
PK characteristics of the drug

Question 10

Transplant

Answer 10

Eye, blood easy

Lung difficult

Question 11

Isograft

Answer 11

Genetically identical

Question 12

Autograft

Answer 12

Same individual

Question 13

Allograft

Answer 13

Same species

Question 14

Cyclosporine ADME

Answer 14

Variable oral bioavailability
Highly bound to plasma lipoproteins
3A4 metabolism
Bile elimination

Monitor trough concentration for dose individualization

AE nephrotoxicity

No clear relationship between concentration and the risk of rejection

Question 15

Tacrolimus

Answer 15

Incomplete and variable absorption
Food decreases absorption
Highly bound
Bile elimination

3A4 and 3A5 metabolism

AE: nephrotoxicity, neurotoxicity

Increased with PPI

Question 16

3A5 metabolism

Answer 16

African American have more functional 3A5 and can metabolize tacrolimus better

Question 17

Mycophenolic acid

Answer 17

MMF prodrug, teratogen

Question 18

Sirolimus

Answer 18

mTOR inhibitor

Linear dose PK proportionality

3A4 metabolism, pgp efflux
Long half life, needs loading dose

Question 19

3A4 inhibitors increase concentration

Answer 19

Erythro macrolides
CCB diltiazem verapamil
Azole antifungal
Grapefruit juice

Question 20

3A4 inducers decrease concentration

Answer 20

Anticonvulsant pheny, pheno, carbamazepine

Glucocorticoids, rifampin, SJW

Question 21

Theophylline

Answer 21

Antiinflammatory, steroid sparing
Half life shorter in children (higher clearance) higher Vd

Activates HDAC gene repression

Absorption is variable, not influenced by food
Binds to albumin
1A2 metabolism
Smoking increases clearance

Question 22

Kidney metabolism

Answer 22

Water soluble molecules

GFR iohexol iothalamate gold standard

MDRD for staging CKD

Renal adjustment for drugs that are 30% renally eliminated

Renal dysfunction decreases 3A4

Question 23

Liver metabolism

Answer 23

Metabolize lipophilic to more water soluble forms then renally eliminated

Child Pugh liver severity ABC
Hepatic encephalopathy
Ascites, albumin
Bilirubin, INR

Question 24

Bile elimination

Answer 24

Non water soluble molecules

Question 25

LogP

Answer 25

Positive lipophilic

Negative hydrophilic

Question 26

Hemodialysis

Answer 26

Removes molecules <500D
Water soluble
Low Vd, unbound drugs

Question 27

Continuous renal replacement

Answer 27

Up to 5000D

Can’t remove large Vd drugs

Sieving coefficient closer to 1 has better passage across filter

Question 28

Immunoassay

Answer 28

Enzyme linked