Toxicology Drug And Monitoring Flashcards
Why would you do use therapeutic drug monitoring?
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
Drugs have a narrow therapeutic range? What happens if the range is wide?
Little risk of toxicity and high doses are tolerated. Drugs are titrated until beneficial effects are established
Drugs have a narrow therapeutic window - what if this is large?
Drugs are toxic at just above their effective range meaning the need monitored
The status of drugs is normally measured by what?
Physiological markers such as people who are using anti-hypertensives will be checked by checking blood pressure.
Why is there a difference between drugs and effect?
There is inter-individual pharmacokinetics and clearance factor changes depending on peoples renal and liver function.
Drugs and effect - can other drugs induce (reduce drug concentration) or inhibit (increase drug concentration) to metabolise enzymes?
Yes
Should drug concentration give accurate information about the logical effect/toxicity or the drug?
Yes
What should drugs have?
Little pharmacological variation
What other thing needs to be measured in the drug plasma levels and clinical effect assay?
Metabolites
What are some examples of the toxic affects of the drug being similar to those seen in the disease?
ataxia versus seizures in epilepsy
Kidney transplant - renal drug toxicity versus transplant rejection from low immunosuppressant drug levels.
When would you use therapeutic drug monitoring (TDM)?
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
When should you take the drug sample?
Before you give the next dose
What type of drug should you give people?
Steady state drug
What are some commonly monitored drugs?
Anticonvulsants - Carbamazepine, phenytoin
Antibiotics - vancomycin, gentamicin
Immunosuppressants - cyclosporine, tacrolimus,
Others - lithium, digoxin
Clinical toxicology - what is common?
Poisoning
What are typical hospital cases of poisoning?
Carbon monoxide,
Alcohol,
Paracetamol,
Prescription drugs,
Salicylate
Specific poison assays - what assays are available 24/7 and what ones are specialist?
24/7 = ethanol, paracetamol.
Specialist = arsenic, lead
Why would you use a specific poison measurement?
- confirm diagnosis of poisoning
- severity of poisoning
- identify is specific treatment is needed
- monitor removal of toxin
- declare brain death
- medico-legal/ forensic reasons
Why would you use supportive investigations after a poisoning assay?
To identify any major organ damage
What tests would you do to assess major organ damage?
U and e’s
Full blood count/ prothrombin time
Glucose
Ca, albumin, mg
Liver function test
Anion gap
Arterial blood gas
CK - cell lysis
drugs of abuse - what type of classes is there?
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
when would you screen for drugs of abuse?
Clinical toxicology
Drug treatment programmes/testing orders
Workplace drug testing
Forensic including post mortem
what type of samples do you get when testing for DOA?
urine = most common
blood = forensic analysis
oral fluid = witnessed collection
sweat
hair = historical use
when do you use immunoassay?
Initial screening test prior to confirmation method.
positive results of immunoassay needs to be confirmed by something else
what do you use for screen do you use for confirmation and why?
GC-MS as it has reproducible retention times, excellent chromatographic resolving power.
what are disadvantages of using GC-MS as a confirmation screen?
- extensive sample preperation - need for derivatisation and extraction
- user expertise in method development, troubleshooting, interpretation
- long run times thus low throughput
what other screens can be used as confirmation?
tandem mass spec
what are the advantages of tandem mass spec over GC?
-Allows simultaneous detection of multiple compounds,
- Can analyse polar, non-volatile, heat labelled compounds,
- No need to derivatise
- Quicker run times
what are disadvantages of tandem mass spec over GC?
- Occasionally requires extensive sample preperation i.e. hydrolysis and extraction (really only canabis)
- Instrumentation is more expensive
how does tandem mass spec work?
analyte elutes from column
Parent ion travels along first quadropole
Fragmetned in second quadrupole by collision gas
Product ions travel aling third quadrupole
do you get false positives in tandem mass spec?
no
when doing a tandem mass spec how do you know its been done right?
retention times match internal standard
Peaks are same shape
Ratio of quantifyinf: qualifying match calibrators
all peaks must be confirmed or deleted
