Drug Toxicity Flashcards
Factors that can influence the development of drug-induced adverse effects (9)
PK of the drug Dosage Age/gender Genetics Body weight and fat Smoking/drinking Health status Other drugs Allergies
Too high of a dose on target
Could cause an unwanted amount of effect, chronic receptor activation/inhibition, or bind the right receptor in the wrong tissue
Right dose on target causing toxicity
Alteration in drug parameters from kidney/liver failure and drug interactions
Increase in receptor number/sensitivity
Extended exposure
Drug toxicity from off-target effects
High affinity for unintended receptor in tissue needing therapy
Binding to unintended target in unrelated tissue
Enantiomers cause off-target effects
Overdose of acetaminophen
Can cause hepatotoxicity: N-acetyl benzoquinoneimine is usually reduced by glutathione and excreted, but the capacity of glutathione is exceeded in overdose and the N-acetyl benzoquinoneimine is free to react with hepatocytes and cause damage.
How is acetaminophen overdose treated, and how does it work?
With N-acetyl cysteine - it increases glutathione levels
How do drug allergies originate?
Metabolites can covalently react with proteins and cause immune reactions, which causes hypersensitivity to the drug or structurally related drug
What is the greatest predictor of idiosyncratic response?
Genetic factors; most likely due to inability to clear toxic metabolites
Categories of drugs during pregnancy
A, B, C, D, X
Category A
Perfectly safe
Category B
Animal trials were safe but there’s no human data
Category C
Animal reproduction studies have shown adverse effects, but no data for humans; may be worth it still
Category D
Evidence of fetal risk, but may still be worth the risk
Category X
Linked to fetal abnormalities and the risks will not outweigh the benefits
