Intro to toxicology Flashcards
How is the environment attributed to human diseases?
Many human diseases attributed to incompatibility between our current environment and the environment for which our genome is adapted
Define toxicology
The branch of science concerned with the nature, effects and detection of poisons
Define mithridatic
Tolerance/immunity via progressively increasing dosing (antidote)
What did the dude Paracelsus say about doses (grandfather of toxicology)
All things are poison and nothing is without poison, only the dose permits something not to be poisonous
Describe concept of dose response
There is a line between therapeutic effect and toxic effect - and increasing dose leads one to the other
Define xenobiotic (opposite to endobiotic)
any foreign substance to our body
Define toxic agent
agent that can cause toxicity
Define poisons
Agents that produce toxicity or even death, generally at low doses
Define toxin
Toxic compounds produced by biological systems
Define intoxication
When a compound reaches values above the safe maximum dose
Define toxic syndrome/ toxidrome
Constellation of toxic effects comprising a set of clinical fingerprints of a group of toxic chemicals
The majority of poisonings are unintentional but majority of deaths secondary to poisoning are intentional - true or false?
true :))
Most poisonings are by ingestion and occur at home - true or false
true :))
What is the most commonly reported poison
Analgesics (painkiller that effects the nervous system)
Which poison is associated with the most deaths
Analgesics!
Which poison is associated with the least deaths?
Hydrocarbons
What is the most common poisonous killer
Carbon monoxide
List the ways of classifying xenobiotics
.Target organ classification
. According to use in public domain (insecticides, food additives, therapeutic drugs)
. According to source (botanical, environment)
. According to effects (pathological, mutagenic, carcinogenic)
. According to physical state (solids, liquids, gases)
. According to biochemical properties (chemical structure, mechanisms of action)
. Exposure (route/ duration and frequency)
Give examples of classifying with target organs
Agents affecting hematopoietic system (anticoagulants), hepatotoxic, nephrotoxic pulmonary, cardiovascular
List the routes of exposure
Oral (popular), Intranasal, inhalation, parenteral
List the different durations of exposure
Acute (<24h) - one exposure or continuous low-dose exposure
Chronic (>3months) continuous or repeated intermittent exposure
Can be single or repeated dose
List the four chemical interactions toxic agents can have
Agonistic
Antagonistic
Potentiation (the effect of one drug is greatly increased by the intake of another drug)/Synergistic (interaction so that the total effect is greater than the sum of the individual effects)
Additive
What types of effect could toxic agents have?
Allergic/hypersensitivity Local vs. symptomatic Idiosyncratic Reversible vs. irreversible Immediate vs delayed Target therapeutic effect
Explain the difference between synergism and potentiation
Synergism is talking about the interaction of two or more substances, while potentiation is talking about a singular substance and how it may act when in a synergy relationship
Reversible vs. irreversible reactions
most drugs are reversible until a critical point is reached - where vital function is compromised or carcinogenic event happens
Local vs Systemic effects
Depend on site of exposure - skin or lungs are frequent targets. Hypersensitivity reactions type I and IV, type II are elicited through oral or parenteral
In what situations will you need to modify the therapeutic regime?
When there is compromised kidney function
In response to the diseased organ
When you want to mimic the toxicity of a compound
List the harmful effects of a toxic compound (terms that are given)
Asphyxiant - reduce oxygen concentration in the air (simple), interference with oxygen transport or utilisation of oxygen (chemical)
Irritant
Corrosive
Narcotic - depression of central nervous system)
Sensitiser - allergic reaction in susceptible people - not easy to identify
Toxic
Carcinogen
Mutagen
Teratogen
What is a graded dose response?
Relationship of an individual test subject or system to increasing and/ or continuous doses of a chemical
What is the quantal dose response determined by/
The distribution of responses to increasing doses in a population of test subjects or systems
It is generally classified as an ‘all or none effect’ where the test system or organisms are quantified as either ‘responders’ or ‘non responders’
What is LD50? (lethal dose)
A statistically calculated dose of a chemical that causs death in 50% of the animals tested
What else can be derived from a quantal dose response curve?
Therapeutic and toxic dose, from ED50 and TD50 (effective and toxic dose)
Define ED50 and TD50
Dose that produces an effective dose in 50% of the population that takes it.
Dose at which tonxicity occurs in 50% of the population that takes it
What are the disadvantages of using LD50
Large numbers of animals are required, doesn’t provide information regarding mechanistic effects
doesn’t suggest complementary or selective pathways
What is the relationship between lethal/toxic and the effective dose calculated and expressed by?
The therapeutic index (TI)
Define Inhibitory concentration (IC50)
Concentration necessary to inhibit 50% of a measured response in an in-vitro system - typically calculated off typical concentration- effect curve
What does the IC50 allow?
Comparisons of concentration of chemicals necessary to inhibit any measurable parameter (cell proliferation, cell synthesis, DNA synthesis
What are the advantages of using IC50
Can replace animal toxicity - more cost efficient and can be more predictive of assessing human clinical toxicity than current animal protocols
What Is the threshold dose?
Point at which toxicity first appears
What does NOAEL stand for?
no observed adverse effect level
What is ADME?
Considers at what rate does the chemical enter the body , what storage and metabolism ensues and subsequent excretion
absorption, distribution, metabolism and excretion
How does toxicokinetics different from pharmacokinetics
Pharmacokinetics - study of drug distribution in physiological compartment
Toxicokinetics - includes study of exogenous compounds (xenobiotics), the adverse effects, passage through the physiological compartments and fate of chemical.
Also includes compartmental toxicokinetics
Define toxicodynamics
Concerns the dynamic interactions of a toxicant with a biological target and its biological effects
