principles of toxicology SDL Flashcards
define toxicology
The study of harmful properties, actions and effects of chemicals on biological systems.
define toxin
a substance produced by a living organism (as a bacterium) that is very poisonous to other organisms and that usually causes antibody formation
define toxicant
Any toxic substance, usually man made or a product of man made activities
define poison
a substance that is capable of causing the illness or death of a living organism when introduced or absorbed.
define venom
A poisonous substance/secretion containing one or more toxins secreted by an animal, usually injected into prey or aggressor by biting or stinging
define toxicity
The extent to which something is poisonous or harmful.
define xenobiotic
A chemical substance within an organism that is not naturally expected or foreign
define toxicosis
a pathological condition caused by the action of a poison or toxin.
define developmental toxicity
Adverse toxic effects to the developing embryo or foetus. Toxicant exposure to either parent before conception or to the mother and the developing embryo-foetus.
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 questions are important to ask in a case of suspected poisoning
- WHAT? What is the animal doing? (Clinical signs)
- WHAT? What is the suspected poison?
- WHEN? When did the poisoning happen? How many hours have passed
- WHO? Did anyone see what happened?
- WHO ELSE? Are there any other animals or humans who have/could access the poison and are in danger?
- HOW? How did it get the poison? E.g swallowed, injected, bitten, touched.
- HOW? How did it come into contact with the poison in the first place?
- HOW? How much poison has the animal received?
list ways in which toxicants are absorbed
- GI tract (ingestion)
- skin (absorption/contact)
- inhaled
- mucous membranes
- uterus
- injection
describe how toxicants get distributed around the body
- may have effect locally OR
- travel via the blood
- toxin deposited in tissue depends on receptor types
- ease of distribution affected by toxin solubility (fat vs water)
where do toxicants go once they have been distributed around the body
- lipid soluble chemicals tend to accumulate in fatty tissue
- where the toxin is stored is not necessarily the site of toxcitity
outline how the body gets rid of toxins
- metabolised to a less or more (lethal synthesis) toxic metabolite
- most toxins excreted via kidneys but can also be excreted via milk or sweat
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 effect 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?
ratio of the acute to chronic LD50 dose
example: a compound may have a low acute toxicity, but if it accumulates in the tissue, it can lead to chronic toxicity = cumulative poisons
A CF of >2 suggests a drug is relatively cumulative
- gives an indication of cumulative danger
what is acute toxicosis
refers to effects during the first 24-hour period.
what is chronic toxicosis
Effects produced by prolonged exposure (≥3 months) are referred to as chronic toxicosis.
what is tolerance in terms of toxicity
ability to show less response to a specific dose with repeat exposure - an acquired response, not innate response
how does tolerance to toxin develop
- repeated binding between receptor and substance desensitises receptor
- increase in degradation enzymes reduces amount of substance reaching target tissue
what is resistance
is development of the ability to withstand the previously destructive effect of a drug by microorganisms
how can resistance develop
- Antibiotic inactivation or modification
- Alteration of target or binding site
- Bypassing metabolic inhibition
- Preventing antibiotic accumulation
What are the possible methods of reducing further absorption of toxin?
- wash off if possible
- induce emesis if possible (unless would damage esophagus)
- lavage stomach?
- gastro-protectants or absorbant meds (charcoal)
what supportive treatment is needed in toxicosis
Supportive therapy is often necessary until the toxic agent can be metabolized and eliminated. The type of support required depends on the animal’s clinical condition. Supportive efforts may include:
- control of convulsive seizures
- maintenance of respiration
- treatment for shock
- correction of electrolyte imbalance and fluid loss
- control of cardiac dysfunction
- alleviation of pain.
