Lesson 2

Question 1

Definition of poison, toxicant and toxin

Answer 1

• Poison: substance that causes immediate death or disease after assumption of any dose.
• Toxicant: a substance that produces an adverse event of any nature.
• Toxin: specific protein produced by living organisms, generally with immediate effects

Question 2

How can we classify toxicology according to their objectives?

Answer 2

• Descriptive: to define toxicological test and to classify chemical substances based on their toxicity
• Mechanistic: to study how chemical substances or physical agents can start biochemical or physiological modifications that bring to the toxic event
• Applied: clinical, environmental, medical…

Question 3

How can be mediated a toxic response?

Answer 3

• Receptor response: high doses cause disfunction in the receptor. For example, high doses of benzodiazepines can affect GABA A receptor and provoke a progressive depression of CNS to comatose state
• No receptor response: an example are free radicals which can lead to membrane permeability and DNA modifications
• Mixed response: such as for heavy metal. They can modify membrane fluidity, DNA by intercalation and also inhibit some enzymes

Question 4

Which are the main differences in drugs and xenobiotic kinetics according to age?

Answer 4

In particular, absorption is different in adult ages: the gastric pH level reach a typical adult level only at 3 years old, therefore substances with acid or alkaline pKa are absorbed differently in babies.
Also, distribution changes: there’s a qualitative difference in albumin concentration from child (lower) to adult (higher).

Question 5

Definition of toxification

Answer 5

conversion of a chemical compound into a more toxic form in living organisms. The conversion can be caused by enzymatic metabolism in the organism, as well as by free radicals.

Question 6

Definition of detoxification

Answer 6

The physiological or medicinal removal of toxic substances from a living organism, which is mainly carried out by the liver.
Toxins enter through the lungs, the skin and the intestine, then they exit through the lungs (expiration), the colon (defecation), the skin (perspiration) and the kidneys (urination).

Question 7

Which test must be performed during pre-clinical research?

Answer 7

• Acute testing: daily examination of the animals for signs of intoxication, behavioural modification…
  It give a quantitative estimate of acute toxicity (LD5) and it’s necessary to identify target organs and species differences.
• Sub-acute testing: repeated administration (typically for 14 days)
• Sub-chronic testing: exposure last 90 days. You can determine NOAEL (no observed adverse effect levels) and LOAEL (lower observed low effect level).
  They’re conducted on 2 species.
• Chronic testing: from 6 months to 2 years. To assess both the cumulative toxicity and the carcinogenic potentials. You have to calculate the MTD (maximum tolerable dose)

Question 8

Which are the phases of clinical research?

Answer 8

Phase 1: in healty volunteer subject. To determine the metabolic and pharmacologic actions of the drug in humans
Phase 2: it include early controlled clinical studies done to obtain preliminary data of effectiveness
Phase 3: studies are expanded to more patient with the disease or condition
Phase 4: pharmacovigilance