Lecture 11 Flashcards
what are biomarkers ? give examples
Measurable substance or alteration which is used to detect a disease or change of the normal physiological condition.
enzymes, metabolites, MRI parameters, change in endogenous substances concentrations, altered ratios, newly formed substances
why biomarkers in forensic toxicology ?
if short detection window, gives proof of intake, display consumption behaviour, easier detection in special matrices
differences between direct and indirect biomarkers
direct :
- formation through metabolism
- phase II metabolites
- basic framework of target compound can be found in structure of biomarker
indirect :
- changes in the body due to substance intake
- concentrations of enzymes / endogenous substances
- pathological change after permanent consumption
2 of the most used alcohol biomarkers, characteristics
EtG :
- small
- blood, urine, hair
- detection window depends on matrix (short in blood, long in hair)
PEth :
- group of molecules
- in blood (in erythrocytes) -> dried blood spots
- detectable up to 4 weeks (depending on the consumption)
DBS technique : sampling, principle, procedure of analysis
- venipuncture or capillary blood (finger prick)
- distribute blood on sample paper -> punching out -> extraction with suitable solvent
- chromatographic separation and then MS
some advantages of DBS technique
- easy, home sampling
- less invasive, less infection
- storage at room temp
- economically friendly
- redefinement / reduction / replacement
what is one problem with DBS technique ? what is the effect of drop size ?
hematocrit (concentration of RDB) has an impact on drop size : the higher %, the smaller the drop.
The accuracy increases with the %.
The concentration is not the same everywhere in the drop -> position of punch has an influence.
3 types of NPS (new psychoactive substances)
1) slight alteration of known substance
2) semi-synthetic
3) new structure but same target in the body
main problems of NPSs
- unknown effects -> not predictable
- positive tests without proof
- forensics is always one step behind of illegal market -> new patterns in metabolimics ?
how could biomarkers help in traumatic brain injury for example ?
If there is a lack of macroscopic signs, or lack of conditions concerning death -> release of biomarkers as reaction to traumatic effect.
There is a great variability in the biomarkers we could use.
3 aspects of an ideal biomarker
- expression increased in related disease condition
- quantifiable in matrix
- not expensive, consistent
3 types of biomarkers (0, 1, 2)
0 : natural history of a disease (ex insulin levels)
1 : effects of intervention with drug
2 : surrogate endpoints as a change in that marker that predicts medical benefit
what is an efficacy biomarker and the 4 groups
demonstrate a change in a good proportion of treated subjects. The more positive the marker, the higher the efficacy.
- surrogate endpoints
- predictive
- pharmacodynamic
- prognostic
what is a surrogate endpoint ?
lab or physical measurement used in clinical trials to indicate a drug’s response and can be used in place of a clinical endpoint.
Assess benefit or harm of therapeutic agent.
what are pharmacodynamic markers ? (example)
indicators of a drug’s pharmacological effect on its target(s).
ex : target is a receptor that initiates a signaling cascade. Changes in the levels of proteins along the signaling cascade is a PD marker.
