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Biomedical Toxicology > Biomedical Tox. > Flashcards

Biomedical Tox. Flashcards

1
Q

What is biomedical toxicology?

A

The study of the adverse effects of chemicals on living organisms.
- The interactions and effects of exogenous agents on processes at the organ, cellular, and molecular levels.

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2
Q

What is a toxicant?

A

An agent capable of producing a deleterious response in a biological system.

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3
Q

What is an organism?

A

Has target sites, storage depots, and metabolic enzymes

- Toxins are exogenous agents that interact with proteins, lipids or nucleic acids in cellular targets.

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4
Q

What is an adverse effect?

A

Any change from an organism’s normal state,

- Depends on the concentration of active compound at the target site for a sufficient time; have to be exposed.

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5
Q

What is a poison?

A

A substance that is capable of causing the illness or death of a living organism.
- Are toxic substances not directly of biological origin.

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6
Q

What is a toxin?

A

Any chemical that can injure or kill a living organism.

  • Toxins are biologically produced.
    ex. Venom, Mycotoxin, Exotoxin
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7
Q

What is the study of pharmacology?

A

The study of the entire effect of a “drug” on the function of a living system.

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8
Q

What is the study of pharmacokinetics?

A

Examines drug absorption, distribution, metabolism, and excretion within an organism.
- Related to toxicokinetics.

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9
Q

What is the study of pharmacodynamics?

A

Studies drug interactions with biological receptors (endpoint interaction).

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10
Q

What is the study of toxicology?

A

The study of the effects of xenobiotics (foreign substances) on the function of a living system.
- A subset of pharmacology.

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11
Q

What is the study of toxicokinetics?

A

Drug movement around the body: absorption, distribution, metabolism, and elimination of a xenobiotic.

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12
Q

What is the study of toxicodynamics?

A

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

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13
Q

What are examples of exogenous agents?

A

Drugs, Insecticides, Plant and Animal toxins, Industrial chemicals, Particulates, and Radioactive elements.

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14
Q

How are animals exposed to toxic elements in labs?

A

Application to the skin, inhalation, or gavage.

  • Want to mimic human exposure as much as possible.
  • By placing the test material in the water or air of the test animals’ environment.
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15
Q

What was the Bhopal Gas Tragedy?

A

Methyl isocyanate gas was released killing thousands.

  • Tear gas, extremely toxic and odourless, causes crying.
  • A lachrymal agent.
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16
Q

How is toxicity measured?

A

As clinical “endpoints” which include any disruption to an organism’s homeostasis (wellbeing).

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17
Q

What is the endpoint of an acute study?

A

LD50

Note: an LD50 with a low number indicates high toxicity.

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18
Q

What is the endpoint of a chronic study?

A

Reproduction, long-term survival, and growth.

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19
Q

The extent to which something is toxic depends on…

A

Various things such as subject variability, route of exposure, duration, frequency, amount, target within an organism (organ, tissue, cell type), bioavailability and bioaccumulation.

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20
Q

What is bioavailability?

A

The proportion of a substance that enters circulation when introduced into the body and is able to have an effect.

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21
Q

What is bioavailability dependant on?

A

Exposure, solubility, physical state, and chemical state.

22
Q

Which is more toxic: Methyl mercury or Ethyl mercury?

A

Methyl mercury.

23
Q

How is MeHg-L-cysteine transported?

A

Actively transported across the blood-brain barrier.

- May indicate why high levels of Hg are found in the brain after exposure.

24
Q

What are the attributes of a target molecule?

A

All endogenous molecules, generally those:

  • Involved in a critical pathway; susceptible to reactions
  • Are reactive
  • Are accessible to the toxicant at high enough concentrations
25
Q

What are examples of target molecules?

A

Proteins (major), nucleic acids, lipids, and cell membranes.

26
Q

What are the reaction types with target molecules?

A

Noncovalent binding: Reversible, lock and key inhibitors with membrane receptors and enzymes.
ex. DNA intercalators

Covalent binding: Irreversible, permanently alters target, reacts with nucleophilic centers in DNA and proteins.
ex. Carbon monoxide

27
Q

What are the effects on a target molecule?

A

Dysfunction: alteration of target conformation
- tertiary protein structure or DNA template

Destruction: crosslinking of proteins and nucleic acids
- fragmentation and degradation

Neoantigen formation: Formation of reactive intermediate

28
Q

What is toxicokinetics concerned with?

A

What the body does to the toxicant.

29
Q

What is bioactivation?

A

When the original form of the toxicant undergoes metabolic activation to the toxicologically active form.

30
Q

What are the processes of toxicokinetics?

A

Xenobiotic > Absorption > Distribution > Metabolism > Exretion

31
Q

What are the routes of absorption?

A

Inhalation via the lungs.
Direct contact via the skin or eyes.
Ingestion via the GIT.
Injection via direct puncture of the skin.

32
Q

How do chemicals enter the body?

A

Must cross a biological membrane by passive diffusion or active transport.

33
Q

Characteristics favouring absorption: inhalation

A

Large surface area, large blood supply, migration.

34
Q

What does toxicity through the pulmonary route depend on?

A
  • Particulate size and volatility (ability to vapourize)
  • Ability to diffuse
  • Affinity for transporters
35
Q

Characteristics of dermal route

A

Protect against external environment: No pores, tight intercellular junction, no transport systems (diffusion mediated), low blood flow (low in epidermis, higher in dermis).

36
Q

How can dermal absorption be increased?

A

Hydration, solvent effects, temperature.

37
Q

Characteristics favouring absorption: ingestion

A

Single-cell lipoidal membrane, large surface area, high blood and lymph flow, variable pH, many specialized transport proteins (not diffusion dependent)

38
Q

What is uptake by passive diffusion?

A

Does not require energy, most common way xenobiotics cross cell membranes.

Rate is determined by differences in concentration and ability to move through pores in the membrane (small water-soluble molecules and water, ex. ethanol) or across the lipophilic interior (high lipid solubility readily diffuse, like dissolves like, ex. DDT, steroids).

39
Q

What is uptake by facilitated transport?

A

Carrier-mediated; does not require energy.

  • Faster than passive transport and can move larger molecules
  • Follows a concentration gradient
40
Q

What is uptake by active transport?

A

Involves a specific “carrier” protein which transfers the xenobiotic across the plasma membrane.

  • Requires energy (ATP)
  • Can move against concentration gradient
  • Rate is limited by the number of carriers
  • Important in the elimination of substance via the kidney and liver
41
Q

The rate of distribution (translocation) to organs or tissues is determined by:

A

Note: Distribution normally occurs very rapidly
1. Properties of the chemical
2. Blood flow
3. Rate of diffusion
4. Affinity of xenobiotic for various tissues
5. Protein binding
6. Penetration by diffusion or active transport
Also, the size of a toxicant dictates where it can go in the body

42
Q

What are some protein binding sites?

A

Albumin, transfer protein, erythrocytes, lipoproteins, globulins.

43
Q

What is binding site competition?

A

Displacing bound toxin > Free toxicant > Toxicity

44
Q

What is the effect of binding?

A

Increased binding > Decrease free toxicant concentration (lower toxicity) > lower elimination

45
Q

What barriers prevent distribution?

A

Blood brain barrier (BBB)
Blood placenta
Blood testis
- Highly protected location in the body possess barriers to control their environment
- Have no pores, tight intracellular junctions, degrading enzymes and thick lipoidal barriers
Importance: Slow rate of distribution to these copartments > allows for increased time for elimination

_

46
Q

What is methyl mercuric cysteine?

A

Can travel across the BBB and cause neurotoxicity.

Methymercury + cysteine = structure similar to methionine

47
Q

Blood brain barrier

A
  • ATP dependent MRP to transport xenobiotics back into blood
  • Low protein content > limits transport of bound toxins
  • Secrete chemical factors > control permeability and restrict access
  • Cells are tightly joined leaving few or no holes
48
Q

What does toxin storage do?

A

Accumulates toxins in specific tissues (liver, fatty tissues, bones):

  1. Reduce toxicity by taking toxic substances out of the sites of action
  2. Increases toxicity if a) toxicity at the storage site, b) displacement of one substance by another and loss of storage site
  3. Produces chronic toxicity from prolonged exposure
49
Q

What organs aid in the removal of toxins?

A

Kidney (urine) - Filtration and active secretion
Liver/Bile (waste) - active secretion
Lungs (air)
Mammary (gland milk)
Sweat glands (sweat) Diffusion into glandular secretions
Salivary glands (saliva)

50
Q

What are characteristics favouring exretion?

A
  1. Low lipid solubility
  2. Ionized = water soluble
  3. Non protein bound > Free toxin
  4. Low molecular weight > Kidney
  5. High molecular weight > Liver > Bile
51
Q

How can exertion fail?

A
  1. Lipid soluble - Storage = Bioaccumulation
  2. Reabsorbed - Kidney (Hg-metalothionine)
    Reabsorbed - GIT = (bile salts) active transport
  3. Binding - storage = Bioaccumulate (lead)

Biomedical Toxicology (1 decks)

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