Principles of toxicology SDL Flashcards
What are the possible effects of toxicity?
cell replacement, such as fibrosis
Damage to an enzyme system
Disruption of protein synthesis
Production of reactive chemicals in cells
DNA damage
When does a chemical become toxic?
Xenobiotic (foreign) compound enters the body and absorption exceeds elimination
What is LD50?
the lethal dose required of a substance that kills 50% of the test population
Lower LD50 = more toxic
What are the routes of absorption of toxins into the body?
Describe the distribution of toxins in the body
May have local effect
Can travel via blood stream
Deposition in tissue depends on receptor sites
Ease of distribution is affected by toxin solubility
How does the body get rid of toxins?
Metabolised to a less or more (lethal synthesis) toxic metabolite
excretion via kidneys
What is lethal synthesis?
When a toxin becomes more toxic following metabolism
Describe the metabolic pathway for elimination of fat soluble toxicants
Lipophilic toxin binds to lipoproteins in the blood
Undergoes metabolism in liver
Phase I metabolism:
- oxidation
- reduction
- hydrolysis
Phase II metabolism:
- synthetic conjugation
Increased water solubility
Excreted in bile or urine
what factors affect toxicity?
Dose
Duration + frequency of exposure
Age and health of patient
route of exposure
Environmental factors
Inability to vomit
Seasonal or climatic changes
Isomer of toxin
what is chronicity factor?
The ratio of the acute to chronic LD50 dose of a toxin
CF>2 suggests the drug is cumulative
e.g., a compound may have low acute toxicity by can lead to chronic toxicity if it accumulates in the tissue
What is the difference between acute and chronic toxicosis
What is tolerance in toxicity?
ability to show less response to a specific dose with repeat exposure
(acquired response, not innate)
How can tolerance to a toxin develop?
repeated binding between receptor and substance desensitises receptor
Increase in degradation enzymes reduces amount of substance reaching target tissue
What is resistance in toxicity?
development of the ability to withstand the previously destructive effect of a drug by microorganisms or tumor cells
