Intro to toxicology

Question 1

How is the environment attributed to human diseases?

Answer 1

Many human diseases attributed to incompatibility between our current environment and the environment for which our genome is adapted

Question 2

Define toxicology

Answer 2

The branch of science concerned with the nature, effects and detection of poisons

Question 3

Define mithridatic

Answer 3

Tolerance/immunity via progressively increasing dosing (antidote)

Question 4

What did the dude Paracelsus say about doses (grandfather of toxicology)

Answer 4

All things are poison and nothing is without poison, only the dose permits something not to be poisonous

Question 5

Describe concept of dose response

Answer 5

There is a line between therapeutic effect and toxic effect - and increasing dose leads one to the other

Question 6

Define xenobiotic (opposite to endobiotic)

Answer 6

any foreign substance to our body

Question 7

Define toxic agent

Answer 7

agent that can cause toxicity

Question 8

Define poisons

Answer 8

Agents that produce toxicity or even death, generally at low doses

Question 9

Define toxin

Answer 9

Toxic compounds produced by biological systems

Question 10

Define intoxication

Answer 10

When a compound reaches values above the safe maximum dose

Question 11

Define toxic syndrome/ toxidrome

Answer 11

Constellation of toxic effects comprising a set of clinical fingerprints of a group of toxic chemicals

Question 12

The majority of poisonings are unintentional but majority of deaths secondary to poisoning are intentional - true or false?

Answer 12

true :))

Question 13

Most poisonings are by ingestion and occur at home - true or false

Answer 13

true :))

Question 14

What is the most commonly reported poison

Answer 14

Analgesics (painkiller that effects the nervous system)

Question 15

Which poison is associated with the most deaths

Answer 15

Analgesics!

Question 16

Which poison is associated with the least deaths?

Answer 16

Hydrocarbons

Question 17

What is the most common poisonous killer

Answer 17

Carbon monoxide

Question 18

List the ways of classifying xenobiotics

Answer 18

.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)

Question 19

Give examples of classifying with target organs

Answer 19

Agents affecting hematopoietic system (anticoagulants), hepatotoxic, nephrotoxic pulmonary, cardiovascular

Question 20

List the routes of exposure

Answer 20

Oral (popular), Intranasal, inhalation, parenteral

Question 21

List the different durations of exposure

Answer 21

Acute (<24h) - one exposure or continuous low-dose exposure
Chronic (>3months) continuous or repeated intermittent exposure

Can be single or repeated dose

Question 22

List the four chemical interactions toxic agents can have

Answer 22

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

Question 23

What types of effect could toxic agents have?

Answer 23

Allergic/hypersensitivity
Local vs. symptomatic 
Idiosyncratic 
Reversible vs. irreversible 
Immediate vs delayed 
Target therapeutic effect

Question 24

Explain the difference between synergism and potentiation

Answer 24

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

Question 25

Reversible vs. irreversible reactions

Answer 25

most drugs are reversible until a critical point is reached - where vital function is compromised or carcinogenic event happens

Question 26

Local vs Systemic effects

Answer 26

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

Question 27

In what situations will you need to modify the therapeutic regime?

Answer 27

When there is compromised kidney function In response to the diseased organ When you want to mimic the toxicity of a compound

Question 28

List the harmful effects of a toxic compound (terms that are given)

Answer 28

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

Question 29

What is a graded dose response?

Answer 29

Relationship of an individual test subject or system to increasing and/ or continuous doses of a chemical

Question 30

What is the quantal dose response determined by/

Answer 30

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'

Question 31

What is LD50? (lethal dose)

Answer 31

A statistically calculated dose of a chemical that causs death in 50% of the animals tested

Question 32

What else can be derived from a quantal dose response curve?

Answer 32

Therapeutic and toxic dose, from ED50 and TD50 (effective and toxic dose)

Question 33

Define ED50 and TD50

Answer 33

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

Question 34

What are the disadvantages of using LD50

Answer 34

Large numbers of animals are required, doesn't provide information regarding mechanistic effects doesn't suggest complementary or selective pathways

Question 35

What is the relationship between lethal/toxic and the effective dose calculated and expressed by?

Answer 35

The therapeutic index (TI)

Question 36

Define Inhibitory concentration (IC50)

Answer 36

Concentration necessary to inhibit 50% of a measured response in an in-vitro system - typically calculated off typical concentration- effect curve

Question 37

What does the IC50 allow?

Answer 37

Comparisons of concentration of chemicals necessary to inhibit any measurable parameter (cell proliferation, cell synthesis, DNA synthesis

Question 38

What are the advantages of using IC50

Answer 38

Can replace animal toxicity - more cost efficient and can be more predictive of assessing human clinical toxicity than current animal protocols

Question 39

What Is the threshold dose?

Answer 39

Point at which toxicity first appears

Question 40

What does NOAEL stand for?

Answer 40

no observed adverse effect level

Question 41

What is ADME?

Answer 41

Considers at what rate does the chemical enter the body , what storage and metabolism ensues and subsequent excretion absorption, distribution, metabolism and excretion

Question 42

How does toxicokinetics different from pharmacokinetics

Answer 42

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

Question 43

Define toxicodynamics

Answer 43

Concerns the dynamic interactions of a toxicant with a biological target and its biological effects