L19: Intro to Toxicity Flashcards
3 important principles in toxicology
1) Toxic effects are dose-dependent
2) Sensitivity varies between species & individuals
3) Acute & chronic effects may involve different mechanisms
Define LD50
Amount of substance estimated to kill 50% of the test population in a single dose
Factors affecting LD50
Route of administration
Species variation
How is LD50 determined ?
Dose-response curve
- lethality in x-axis
Define therpeutic index
ratio of LD50 to ED50
OR
ratio of TD50 to ED50
What is the relationship between the value of therapeutic index and the margin of safety between pharmacological dose & toxic dose?
Large the value, greater the margin of safety
Define TD50
Dose at which 50% experiences toxic effects
Define LD50
Dose at which 50% of subjects die
Explain the comparision of toxicity
2 substances can have the same LD50, but 1 may be more hazardous if dose-response curve is steeper
4 categories of drug disposition (ADME)
Absorption
Distriubtion
Metabolism
Excretion
What does alterations in any phase of drug disposition affect?
Efficacy & toxicity
Define toxin
Natural poison from plants/animals
Examples of types of toxic substance
1) Drugs
2) Industrial chemicals
3) Food additives & contaminants
4) Pesticides
5) Natural products
6) Household products
7) Environmental pollution
Define toxicant
Man-man poison
Acute effects of alcohol toxicity
CNS depression, impaired coordination, vomiting, hangover, unconsciousness
Chronic effects of alcohol toxicity
Chronic: long-lasting
Brain damage cancer
What is Botulinum Toxin (Botox) produced by?
Clostridium Botulinum (found in low-oxygen, low-acid foods)
Effects of Botulinum Toxin (Botox)
1) Poisoning (botulism): muscle paralysis, blurred vision, can’t speak
Mechanism of Botulinum Toxin (Botox)
Blocks neuromuscular transmission through decreased release of acetylcholine
Medical uses of Botulinum Toxin (Botox)
1) Treats spasms
2) Excessive blinking, sweating
3) Paralysis of facial muscles
Metabolism of paracetamol toxicity
Conjugated with sulfate & glucuronic acid, minor metabolism of oxidation, then conjugated with glutathione
What happens if there is an overdose of paracetamol?
Saturation of conjugation pathway, resulting in more oxidative metabolism & depletion of glutathione
How can glutathione be regenerated (antidote)?
N-acetylcysteine acts as an antidote
What is aspirin metabolised by?
esterases to salicylic acid, then conjugated with glucuronic acid/glycine
