Toxicology
- Created by: SamDavies
- Created on: 11-01-19 23:40
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- Toxicology
- Cellular toxicity
- GSH is an anti-oxidant
- GSH also removes paracetamols reactive metabolite from the body
- Phenols are electron rich - can be oxidised to quinones (highly reactive with GSH)
- Depletion of GSH, increases reactive oxygen species
- Liver toxicity
- Depletion of GSH causes NAPQI accumulation
- Leads reactions between the excess of quinone with proteins in the liver
- The exogenous species would cause an anti-inflammatory immune response where liver attacks itself
- Drug-Drug Interactions
- CYP450 enzymes
- Phase I oxidation in the liver
- CYP450 inhibitors bind strongly to metal centre of haem group
- CYP450 inhibitors are unhindered aromatic nitrogens
- CYP450 inhibitors will make CYP450s unavailable to metabolise certain drugs, causing them to accumulate
- CYP450 enzymes
- Idiosyncratic toxicity
- Type B reactions which occur rarely and unpredictably
- Acyl glucuronides formed from phase II can be unstable, binding to random proteins in the body
- Formed from -COOH
- Increases risk of secondary pharmacology
- This could lead to serious liver injury
- Genotoxicity
- Some active metabolites can bind with DNA causing a genetic mutation
- Anilines and heteroaromatic amines
- Can become oxidised and bind to DNA
- Masked anilines
- Thresholds and margins do not exist for these compounds
- Off-target effects
- Highly lipophilic compounds
- NAIDS block COX2 for anti-inflammatory effects.
- NSAIDS also block COX1, reducting prostaglandin production
- Cellular toxicity
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