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Chapter 1 Flashcards

1
Q

What is potentiation in toxicology?

A

Occurs when a chemical that does not have a specific toxic effect makes another chemical more toxic

Example: Hepatotoxicity of carbon tetrachloride is enhanced by isopropanol

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2
Q

What is additivity in drug interactions?

A

A combination of two or more chemicals is the sum of the expected individual responses

Example: Two CNS depressants taken simultaneously

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3
Q

What is antagonism in toxicology?

A

Exposure to one chemical results in a reduction in the effect of the other chemical

This is often the basis for most antidotes

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4
Q

What is synergism?

A

Exposure to one chemical causes a dramatic increase in the effect of another chemical

Example: Asbestos and cigarette smoke increase lung cancer risk more than each alone

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5
Q

What are the four types of interactions in toxicology?

A
  • Additivity
  • Antagonism
  • Potentiation
  • Synergism
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6
Q

What is the role of cytochrome P450 in metabolism?

A

Cytochrome P450 enzymes are involved in Phase I reactions of biotransformation

They are heme-containing proteins found in the hepatic ER

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7
Q

What is the main goal of Phase II metabolism?

A

To make substances more polar to facilitate excretion

This often involves conjugation reactions

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8
Q

What is the significance of plasma protein binding?

A

Some toxicants bind to plasma proteins like albumin, affecting distribution and half-life

Free toxicant is in equilibrium with bound toxin

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9
Q

What factors affect the distribution of toxicants?

A
  • Physical or chemical properties of the toxicant
  • Concentration gradient
  • Volume of distribution
  • Cardiac output to specific tissues
  • Detoxification reactions
  • Tissue sensitivity
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10
Q

What are the potential results of biotransformation?

A
  • Increase toxicity via a toxic metabolite (toxification)
  • Decrease toxicity via metabolism of a toxic parent compound (detoxification)
  • Production of intermediate metabolites
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11
Q

What is the definition of LD50?

A

The dose that kills 50% of the exposed animals

LD50 can vary among chemicals and animal species

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12
Q

What does the dose-response curve illustrate?

A

As the dose of the toxicant increases, so does the response

Population representation of variability is often shown as a normal distribution

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13
Q

What is the therapeutic index (TI)?

A

TI = LD50 / ED50; the larger the ratio, the greater the relative safety

TI is used to assess the safety of a drug

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14
Q

What is the margin of safety (MOS)?

A

MOS = LD(01) / ED(99); it takes the slopes and extremes of the curves into account

It is a measure of the safety margin of a drug

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15
Q

What are the types of toxic responses?

A
  • Local
  • Systemic
  • Immediate
  • Delayed
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16
Q

What distinguishes reversible from irreversible toxic responses?

A

Reversible responses occur in rapidly regenerating tissue, while irreversible responses often involve permanent damage

Example: CNS damage is typically irreversible

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17
Q

What is the significance of the route of administration in toxicology?

A

Where a toxicant enters the bloodstream affects its toxicity

Different routes include digestive, respiratory, and percutaneous

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18
Q

What is the process of biotransformation?

A

It changes substances from hydrophobic to hydrophilic to aid in elimination

Major elimination route is urine

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19
Q

What types of toxicity studies are conducted?

A
  • Acute toxicity
  • Genotoxicity
  • Sub-chronic and chronic toxicity
  • Carcinogenicity
  • Reproductive toxicity
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20
Q

What is the role of detoxification reactions?

A

They modify toxins to less toxic or more toxic compounds, affecting their overall toxicity

Detoxification is crucial for reducing harmful effects

21
Q

What is the main purpose of toxicity studies?

A

To determine what adverse effects a chemical produces and the dose required to produce each effect

22
Q

What is the significance of the blood-brain barrier in toxicology?

A

It inhibits the migration of toxicants, affecting their distribution and potential toxicity

This barrier is crucial for protecting the brain

23
Q

What are the types of specialty areas in toxicology?

A
  • Neurotoxicology
  • Genetic Toxicology
  • Reproductive Toxicology
  • Immunotoxicology
  • Environmental Toxicology
24
Q

What defines a poison?

A

Any agent capable of producing an adverse response in a biological system

25
What are the two types of toxic responses?
Reversible and Irreversible ## Footnote Reversible toxicity is often associated with rapidly regenerating tissues, while irreversible toxicity can lead to CNS damage, carcinogenesis, mutagenesis, and teratagenesis.
26
What factors influence toxicity?
* Form and innate chemical activity * Dosage * Route of exposure * Species * Age * Sex * Ability to be absorbed * Metabolism (biotransformation) * Distribution within the body * Excretion * Presence of other chemicals
27
What natural carcinogens are found in coffee?
* Acetaldehyde * Acrylamide * Benzaldehyde * Benzene * Benzofuran * Benzo[a]pyrene * Caffeic acid * Catechol * Ethanol * 1,2,5,6-Dibenz-anthracene * Ethylbenzene * Formaldehyde * Furan * Furfural * Hydrogen peroxide * Hydroquinone * Limonene * Styrene * Toluene * Xylene
28
What is the definition of toxicology?
The science that deals with the adverse effects of chemicals on living systems
29
What are the three phases of toxicology?
* Exposure phase * Toxicokinetic phase * Toxicodynamic phase
30
What does the term 'bioavailability' refer to?
The fraction of a dose available for absorption
31
What is the role of the gastrointestinal tract in toxicant absorption?
Absorption of toxicants can take place anywhere, but much of the tissue structure in the digestive system is specially designed for absorption
32
Fill in the blank: The _____ phase refers to the actions and interactions of the toxicant within the organism.
Toxicodynamics
33
Fill in the blank: The _____ phase refers to the process of absorption, distribution, elimination, and metabolism of a toxicant.
Toxicokinetics
34
What are the typical routes of exposure for toxicants?
* Ingestion (GI tract) * Inhalation (Lungs) * Dermal/Topical (Skin) * Injection (i.m., i.p., i.v., s.c.)
35
True or False: Chronic toxicity takes many months or years to become a recognizable clinical disease.
True
36
What is an example of acute toxicity?
Exposure to methyl isocyanate from an industrial accident in India (1989) that resulted in 5,000 deaths
37
What is the Delaney Clause?
A provision stating that any chemical found to be carcinogenic in lab animals or humans cannot be added to the food supply
38
What is the significance of Paracelsus in toxicology?
He formulated views that remain a major part of modern toxicology, pharmacology, and therapeutics
39
What does the term 'acute' refer to in toxicology?
Usually a single dose within 24 hours
40
What is the typical effectiveness of different routes of administration?
i.v. > inhal. > i.p. > i.m. > s.c. > oral > topical
41
What are the effects of particle size on alveolar absorption?
* Particles 5 µm and up are deposited in the nasopharyngeal region * Particles 2-5 µm are deposited in the tracheobronchiolar region * Particles 1 µm and smaller penetrate to the alveolar sacs
42
What is the role of the skin in toxicant absorption?
The skin is the largest organ in the body and provides protection against toxicants
43
What is the effect of ionization on absorption?
At low pH, a weak organic acid is largely nonionized, while a weak organic base is ionized
44
What are the major types of exposure in toxicology?
* Acute * Subchronic * Chronic
45
What is the significance of the Octanol-Water Partition Coefficient, Kow?
It is used to assess transmembrane movement potential of chemicals
46
What does the term 'subacute' refer to?
Repeated exposure to a chemical for one month or less
47
What is the primary focus of mechanistic toxicology?
Understanding why a toxic effect occurs
48
What historical figure ingested a mixture of 36 poisons out of fear of assassination?
Mithridates of Pontus

Tox (3 decks)

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