1 - Intro Flashcards
What is a toxicant?
Any agent that is capable of producing deleterious effects in the body (or organism)
What is a toxin?
A natural product (from plant or animal)
Outline 5 key factors that determine toxicity:
- Dose
- Route of Exposure
- Duration
- Toxicokinetics (esp. metabolism)
- Population
Phosgene (historical and current uses)
Poisonous gas at room temp
* Current: industrial chem for making plastics and pesticices
* Historical: WWI choking agent
Paracelsus take on poisons
The right dose differentiates a poison from a remedy
What are antidotes?
A drug that counteracts the effects of a poison or of overdosage by another drug
Ex. of an antidote to organophosphate poisoning
Pralidoxime + Atropine + Diazepam
* Pral > binds OP and pulls it off of inactivated AChE
* Atropine + Dia > counteract ACh effects
Determining toxic dose
LD50
* Animal: Rat
* Route: Oral
Dose-response curves
Y-axis = response (often % mortality)
X-axis = dose
What is LD50 Vs LC50
LD50 refers to the dose estimated to be lethal to 50% of exposed population. LC50 referes to the concentration.
How can you determine the LD50 from a cumulative mortalty % graph?
Look at the inflection point (x axis)
List the routes of exposure from most effective to least effective for toxicity:
- Inhalation
- Intraperitoneal
- Subcutaneous
- Intramuscular
- Intradermal
- Oral
- Dermal
Exposure duration classification
- Acute (<24h)
- Sub acute (<1 month)
- Sub chronic (1-3 months)
- Chronic (> 3 months)
Describe some toxicokinetic mechanisms that would increase toxicity
- Absorption
- Distribution to target
- Reabsorption
- Toxication - products of metabolism are toxic
Describe some toxicokinetic mechanisms that would decrease toxicity
- Presystemic elimination
- Distribution (efflux)
- Excretion
- Detoxification
Identify some factors in populations that would effect toxicity
- Age
- Sex
- Pregnancy
- Ethnicity
- Species
Toxicological consequences: Dysregulation of gene expression
- Abnormal cell division
- Apoptosis
- Innapropriate protein synthesis
Toxicological consequences: Dysregulation of ongoing cell function
E.g. innapropriate neuromuscular activity
* Tremor
* Paralysis
Toxicological consequences: impaired INTERNAL maintenance
Impaired:
* ATP + protein synthesis
* Ca2+ reg
* Microtubular and membrane function
All lead to cell death/injury
Toxicological consequences: impaired EXTERNAL maintenance
Impaired function of integrated systems
* Hemostasis > bleeding
