Drug Induced Toxicity Flashcards
- Mechanisms of Cell damage - Risk Factors : Liver - Cytotoxic Damage
Mechanisms of Cell Damage : Non - Covalent Interactions
Lipid Peroxidation
Mechanisms of Cell Damage : Generation of ROS
Induce Necrosis / Apoptosis
Mechanisms of Cell Damage : Depletion of Glutathione
Decreases ability of cell to scavenge for ROS
Mechanisms of Cell Damage : Modification of sulfhydryl groups
Reduced enzyme activity like GSH
Mechanisms of Cell Damage : Covalent Interactions w DNA
Results in Genetic Mutation
Risk Factors for Liver Injury
- Age
Elderly people have ↓ clearance, more drug - drug interactions, ↓ hepatic blood flow etc - Alcohol
Cirrhosis leads to ↓ in glutathione, alters metabolic enzyme - Genetics
Polymorphisms exist in CYP450 can result in abnormal reaction to drugs - Liver Disease
Patients w hepatitis, viral infections, cirrhosis, liver cancer at greater risk of toxicity due to drugs - Weight
Body fat can affect distribution of drugs
What is necrosis
Leakage of cytosolic enzymes like ALT
Can be detected in plasma
What’s apoptosis
Cell shrinkage
Nuclear fragmentation w no inflammation
Focal
Randomly distributed death of single hepatocytes
Zonal
Hepatocyte death in functional regions
Panacinar
Massive Death
Few cells remaining
What does hERG do
It codes for the K ion channel
What does the blockage of hERG cause ?
QT prolongation
Biomarker for ventricular tachyarrhythmia
What kind of drugs can cause this
Antipsychotics
Antiarrythmatics
Certain antibiotics like quinolone and macrolides
What does stress induced Ca2+ overload cause
An increase in likelihood of arrhythmia
