Toxicology Drug And Monitoring

Question 1

Why would you do use therapeutic drug monitoring?

Answer 1

1) there is a narrow therapeutic range
2) there is the absence of clinical markers
3) there is a poor correlation between dose and effect
4) there is a good correlation between drug plasma level and clinical effect
5) toxic effects of drugs are similar to presentation of disease

Question 2

Drugs have a narrow therapeutic range? What happens if the range is wide?

Answer 2

Little risk of toxicity and high doses are tolerated. Drugs are titrated until beneficial effects are established

Question 3

Drugs have a narrow therapeutic window - what if this is large?

Answer 3

Drugs are toxic at just above their effective range meaning the need monitored

Question 4

The status of drugs is normally measured by what?

Answer 4

Physiological markers such as people who are using anti-hypertensives will be checked by checking blood pressure.

Question 5

Why is there a difference between drugs and effect?

Answer 5

There is inter-individual pharmacokinetics and clearance factor changes depending on peoples renal and liver function.

Question 6

Drugs and effect - can other drugs induce (reduce drug concentration) or inhibit (increase drug concentration) to metabolise enzymes?

Answer 6

Yes

Question 7

Should drug concentration give accurate information about the logical effect/toxicity or the drug?

Answer 7

Yes

Question 8

What should drugs have?

Answer 8

Little pharmacological variation

Question 9

What other thing needs to be measured in the drug plasma levels and clinical effect assay?

Answer 9

Metabolites

Question 10

What are some examples of the toxic affects of the drug being similar to those seen in the disease?

Answer 10

ataxia versus seizures in epilepsy

Kidney transplant - renal drug toxicity versus transplant rejection from low immunosuppressant drug levels.

Question 11

When would you use therapeutic drug monitoring (TDM)?

Answer 11

New/change in therapy

Compliance - are they taking the drug?

Loss of control in a previously stable patient - often due to changes in metabolism of the drug, drug-drug interactions due to enzyme induction or inhibition. A new onset kidney issue might also cause this.

Post transplant surgery - want to avoid rejection

Question 12

When should you take the drug sample?

Answer 12

Before you give the next dose

Question 13

What type of drug should you give people?

Answer 13

Steady state drug

Question 14

What are some commonly monitored drugs?

Answer 14

Anticonvulsants - Carbamazepine, phenytoin
Antibiotics - vancomycin, gentamicin
Immunosuppressants - cyclosporine, tacrolimus,
Others - lithium, digoxin

Question 15

Clinical toxicology - what is common?

Answer 15

Poisoning

Question 16

What are typical hospital cases of poisoning?

Answer 16

Carbon monoxide,
Alcohol,
Paracetamol,
Prescription drugs,
Salicylate

Question 17

Specific poison assays - what assays are available 24/7 and what ones are specialist?

Answer 17

24/7 = ethanol, paracetamol.
Specialist = arsenic, lead

Question 18

Why would you use a specific poison measurement?

Answer 18

• confirm diagnosis of poisoning
• severity of poisoning
• identify is specific treatment is needed
• monitor removal of toxin
• declare brain death
• medico-legal/ forensic reasons

Question 19

Why would you use supportive investigations after a poisoning assay?

Answer 19

To identify any major organ damage

Question 20

What tests would you do to assess major organ damage?

Answer 20

U and e’s
Full blood count/ prothrombin time
Glucose
Ca, albumin, mg
Liver function test
Anion gap
Arterial blood gas
CK - cell lysis

Question 21

drugs of abuse - what type of classes is there?

Answer 21

Class A drugs - include cocaine, ecstasy, heroin, LSD = these are addictive and cause lots of death

class B drugs- codeine, ketamine = these are slightly less adivtive and causes slightly less death

class c = steroids

Question 22

when would you screen for drugs of abuse?

Answer 22

Clinical toxicology
Drug treatment programmes/testing orders
Workplace drug testing
Forensic including post mortem

Question 23

what type of samples do you get when testing for DOA?

Answer 23

urine = most common
blood = forensic analysis
oral fluid = witnessed collection
sweat
hair = historical use

Question 24

when do you use immunoassay?

Answer 24

Initial screening test prior to confirmation method.

positive results of immunoassay needs to be confirmed by something else

Question 25

what do you use for screen do you use for confirmation and why?

Answer 25

GC-MS as it has reproducible retention times, excellent chromatographic resolving power.

Question 26

what are disadvantages of using GC-MS as a confirmation screen?

Answer 26

• extensive sample preperation - need for derivatisation and extraction
• user expertise in method development, troubleshooting, interpretation
• long run times thus low throughput

Question 27

what other screens can be used as confirmation?

Answer 27

tandem mass spec

Question 28

what are the advantages of tandem mass spec over GC?

Answer 28

-Allows simultaneous detection of multiple compounds,
- Can analyse polar, non-volatile, heat labelled compounds,
- No need to derivatise
- Quicker run times

Question 29

what are disadvantages of tandem mass spec over GC?

Answer 29

• Occasionally requires extensive sample preperation i.e. hydrolysis and extraction (really only canabis)
• Instrumentation is more expensive

Question 30

how does tandem mass spec work?

Answer 30

analyte elutes from column
Parent ion travels along first quadropole
Fragmetned in second quadrupole by collision gas
Product ions travel aling third quadrupole

Question 31

do you get false positives in tandem mass spec?

Answer 31

no

Question 32

when doing a tandem mass spec how do you know its been done right?

Answer 32

retention times match internal standard
Peaks are same shape
Ratio of quantifyinf: qualifying match calibrators
all peaks must be confirmed or deleted