Toxicology II Flashcards
What causes death from hyperhydration?
Hyponatremia causing cerebral edema
What is a lethal dose of Botulinum toxin?
1ng/kg
How is Botox used as a medical treatment?
10ng injected for muscle spasms, cramps & wrinkles
What is the MoA of Botox?
inhibits Ach release
What are adverse drug reactions largely due to?
Imperfect extrapolatability of animal study findings to humans & cutaneous reactions
What are most cytotox assays used for?
late-stage toxicity & cellular events associated with a lethal effect
What are 2 downfalls of cytotox assays?
Low sensitivity for detection of adverse cellular effects
provide little mechanistic understanding of toxicologic effects
What are 6 cytotoxicity tests?
Trypan blue exclusion
neutral red uptake
labelled DNA precursor uptake
LDHA leakage
Tetrazolium salt reduction
HCA 2006
What is HCA/s?
Combines microtiter plate, automation, incubation, microscopic imaging, fluorescent live-cell dye technologies
What happens if membrane permeability increases?
LDH release, ATP depletion & cell rupture
What is the dose-respone curve baseline determined by?
Values at concentrations where no drug or no effect
Which cytotoxicity test correlated the best with human hepatotoxicity?
HCA
What can HCA be used for?
Classic drugs
toxic chemicals
toxins
drug delivery carriers
peptides
nanoparticles
adverse environemental factors
What are benefits seen with using HCA?
reduced market attrition
eliminate toxic moieties
accurate (<5% false +ves)
rapid throughput & relatively inexpensive
elucidation of toxicity mechanisms
What are limitations for predicting human tox potential?
Tox may be mediated by metabolites no by cell lines
Tox may be cell specific
May need to co-culture & 3D models
Edge effects -> high variance
non-adherent cells are difficult to analyse
