Toxicology

Question 1

When should lithium level be checked for monitoring?

Answer 1

At trough - at least 8-12 hours after last dose

Question 2

For TDM of cyclosporin, when is the best time to measure level in relation to dose?

Answer 2

2 hours post dose

Best predictor of AUC if only a single time point is used

Question 3

For TDM of tacrolimus, when is the best time to measure?

Answer 3

At trough – 12 hours after dose

Want to know the steady state concentration

Question 4

CYP enzyme that metabolises Codeine -> Morphine

Answer 4

CYP2D6

Question 5

Major CYP enzyme involved in the metabolism of warfarin

Answer 5

CYP2C9

Question 6

Target enzyme of warfarin

Answer 6

VKORC1

Question 7

Population distribution of TMPT activity

Based on Caucasian population

Answer 7

90%”normal” activity
10% “intermediate”/reduced activity (heterozygote)
<1% have low or undetectable activity (homozygous for inactive TMPT)

Question 8

Azathoprine (pro drug) is converted to..

Answer 8

6-Mercaptopurine (6-MP)

Followerd by anabolism to 6-TGNs

Question 9

Metabolite of thiopurine medications that is therapeutically active but also potentially myelotoxic

Answer 9

6-TGN

6-thioguanine nucleotides

Question 10

What are thiopurine drugs used for?

Answer 10

• Cytotoxics used in treatment of lymphoid malignancies and myeloid leukaemias
• immunosuppressants in autoimmune conditions including IBD, RA, AIH

Question 11

Exogenous factors that can influence TMPT activity (phenotype assessment)

Answer 11

• Recent blood transfusion
• RBC age
• Medications: AZA or 6-MP may induce TMPT activity, such that baseline activity may not predict activity during treatment.
• Salicyclates may inhibit TMPT activity

Question 12

Significance of a low TMPT activity

Answer 12

Increased risk of toxic effects (such as myelosuppression’ hepatotoxicity) from thiopurine medications

Question 13

How do polymorphisms of CYP2D6 affect response to codeine?

Answer 13

Poor metabolisers will mean Codeine not converted to Morphine. Therefore not effective analgesic.

Question 14

How do polymorphisms of CYP2D6 affect response to Metoprolol?

Answer 14

Poor metabolisers will accumulate Metoprolol and there is potential for toxicity

Question 15

Patients who carry which allele should not be prescribed Abacavir

Answer 15

HLA-B*57:01

Increased risk of - DRESS, SJS and toxic epidermal necrolysis (TEN)

Question 16

The presence of the HLA-B15:02 allele is relevant when prescribing what medications?

Answer 16

• Phenytoin
• Carbamazepine

Question 17

What is a chain of custody

Answer 17

a series of procedures to account for the integrity of each sample by tracking its handling and storage from point of collection to disposal

Question 18

Which standard outlines ‘Procedures for specimen collection and the detection and quantitation of drugs of abuse in urine’

Answer 18

AS/NZS 4308

2008 version being updated to 2023

Question 19

Chemical name for cocaine

Answer 19

Methylbenzoylecgonine

Question 20

NUDT15 variants are more common in which population group compared to Caucasians?

Answer 20

East Asian

Question 21

Causes of an increased digoxin level?

Answer 21

• Acute ingestion
• Chronic ingestion
• Renal impairment
• Interference with assay e.g. Digibind/Digibind; Enzalutamide (prostate cancer Rx)

Question 22

How long after digoxin dose should measurement be taken

Answer 22

8 hours post dose (time for blood level to correlate with tissue concentration)