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PHA212 - Introductory Toxicology > Toxicokinetics > Flashcards

Toxicokinetics Flashcards

1
Q

What is toxicity?

A

Toxicity is the intrinsic quality of a chemical to produce an adverse effect. It is the capacity to induce teratogenic, mutagenic and carcinogenic effects

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2
Q

What is a dose?

A

A dose is defined as the amount that ultimately reaches the site or sites of action (tissue, cell, or molecular target)

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3
Q

Xenobiotics need to be absorbed, distributed, bio-transformed, and eliminated. True or false?

A

True

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4
Q

Which xenobiotics don’t need to be absorbed, distributed, bio-transformed, and eliminated?

A

Chemicals which act directly at the point of contact

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5
Q

What is absorption?

A

The process by which toxicants cross body membranes and enter the bloodstream

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6
Q

The main sites of absorption are:

A

The GIT, lungs, and skin

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7
Q

Other possible sites of absorption are:

A

The peritoneum, or muscle, if a chemical is administered by special routes

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8
Q

What is the most common route of unintentional exposure to a toxicant (especially for children)?

A

Accidental ingestion; intentional overdose tends to happen too

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9
Q

What is the condition for poisons in the body to cause injury?

A

Poisons in the GI tract usually do not produce systemic injury to an individual until they are absorbed

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10
Q

Where exactly in the GI tract does absorption occur?

A

Absorption of toxicants can take place along the entire GI tract: from the mouth to the rectum.

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11
Q

How are organic toxicants absorbed?

A

Organic toxicant (acid or base) are usually absorbed by simple diffusion in the part of the GI tract where it exists in its non-ionized form

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12
Q

What is the point of the HH equation?

A

The Henderson–Hasselbalch equations can be used to determine the fraction of a toxicant that is in the non-ionized form and estimate the rate of absorption from the stomach or intestine

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13
Q

Where are organic toxicants more readily absorbed?

A

In the part of the GI tract where they exist in their non-ionized form

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14
Q

What does the HH equation tell us about weak organic acids?

A

According to the HH equation, weak organic acids are mainly present in the non-ionized (lipid soluble) form in the stomach and ionised form in the intestine, thereby more readily absorbed in the former

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15
Q

Factors that affect the HH equation

A

Surface area and Blood flow rate.

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16
Q

Substances which can be absorbed through the GIT’s numerous specialized transport systems (carrier-mediated)

A

Sugar, Iron, Calcium, Thallium, Pb, Co, Mn, and drugs like 5-Fluorouracil, β-lactam antibiotics

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17
Q

Most toxicants are absorbed through…

A

Simple diffusion. Only a few require carrier-mediated transport

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18
Q

Particles and particulate matter can also be absorbed. True or false?

A

Particles and particulate matter can also be absorbed

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19
Q

Relationship between particle size and absorption

A

Size is inversely related to absorption. The smaller the size, the higher the rate of absorption.

For instance, powdered arsenic is significantly more toxic than its coarse granular form - ↑ surface area

20
Q

Characteristics of toxicants affecting their GIT absorption

A
  • Must have sufficient aqueous - lipid partition
  • Be relatively non-ionized in most parts (lipid- soluble)
  • If a particle, must be of relatively low size
21
Q

Factors affecting GIT absorption

A
  1. Other xenobiotics/toxicants: Cd decreases the absorption of Zn and Cu, Ca decreases Cd absorption, and Mg decreases absorption of Fluoride
  2. pH – changes by food, Antacids
  3. GI Motility/residency time within various segments of the GI tract, e.g. the effect of Laxatives/Anti-diarrheas
  4. Age
  5. Presence or absence of digestive enzymes, bile acids, and bacterial microflora in the GI tract
  6. Hepatic first pass effect
22
Q

Example of how age affects absorption in GIT

A
  • Well water with a high nitrate content produces methemoglobinemia more frequently in infants than in adults.
  • Higher pH of the neonatal GI tract is permissive for the growth of bacteria
  • Bacteria in the GI tract convert nitrate to nitrite, increasing the risk of methemoglobinemia
23
Q

Example of how the presence of enzymes, bile acids or bacterial microflora affect absorption

A

Snake venoms are much less toxic by the oral route relative to intravenous exposure because they are broken down by digestive enzymes

Nitroaromatic compounds are reduced by intestinal microflora to potentially toxic and carcinogenic aromatic amines.

24
Q

Results of airborne poisons

A

Death by poisoning

Occupational disease

25
Q

Examples of airborne poisons

A
  • Gases (e.g., carbon monoxide, nitrogen dioxide, and sulfur dioxide)
  • Vapors of volatile or volatilizable liquids (e.g., benzene and carbon tetrachloride)
  • Aerosols
26
Q

Gas molecules do not partition between two media. True or false?

A

False

27
Q

The two media between which gas molecules partition:

A

Air and blood during the absorptive phase and blood and other tissues during the distributive phase

28
Q

Factors affecting absorption in the lungs

A

Factors such as dissociation and lipid solubility of molecules are less important

More important is the blood-to-gas partition coefficient.

29
Q

Example of blood to gas partition coefficient and lung absorption

A

Chloroform has a relatively high blood to gas partition coefficient (approximately 20), whereas ethylene has a low coefficient (0.14), so chloroform will be more easily absorbed

30
Q

How does the blood to gas partition coefficient affect lung absorption?

A

The higher the blood to gas partition coefficient, the higher the lung absorption rate.

High blood-gas partition coefficient just means higher solubility

31
Q

The site of deposition of aerosols and particulates depends largely on…

A

…the size of the particles

32
Q

Relationship between particle size and site of deposition in the respiratory tree, and why

A

The smaller (finer) the particle, the further into the respiratory tree the particle will deposit, because as particle size decreases, the number of particles in a unit of space increases along with the total surface area of the particles

33
Q

What limits exposure and absorption by the skin

A

Its relatively impermeable nature.

34
Q

What is the rate-determining step in skin absorption?

A

Passage through the stratum corneum

35
Q

How do toxicants move across the stratum corneum?

A

By passive diffusion

36
Q

Lipophilic compounds are absorbed less readily across the stratum corneum. True or false?

A

False

37
Q

Relationships affecting absorption of lipophilic compounds in the stratum corneum

A

Absorption rate is proportional to their lipid solubility and inversely related to molecular weight

38
Q

How are hydrophilic compounds likely to penetrate the skin?

A

Through appendages such as hair follicles

39
Q

Factors influencing the absorption of toxicants through the skin:

A
  • The integrity (diffusivity and thickness) of the stratum corneum: caustic agents/Diseases
  • The hydration state of the stratum corneum e.g. occlusive application
  • Temperature: occupational exposure e.g. agricultural workers
  • Solvents as carriers - dimethyl sulfoxide (DMSO)
  • Molecular size (again nanoparticles)
40
Q

Other routes of administration of toxicants:

A
  • Intravenous – 100% absorption
  • Intraperitoneal – Hepatic first pass
  • Subcutaneous – influenced by blood flow/formulation
  • Intramuscular - influenced by blood flow/formulation
41
Q

First pass effect

A

The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemic circulation. It is the fraction of drug lost during the process of absorption which is generally related to the liver and gut wall.

42
Q

The rate of distribution to organs or tissues is determined primarily by…

A
  • Blood flow

- Rate of diffusion out of the capillary bed into the cells of a particular organ or tissue.

43
Q

Some toxicants selectively accumulate in certain parts of the body as a result of…

A
  • protein binding
  • high solubility in fat
  • nature of tissue, eg
  • Lungs e.g. paraquat accumulates in the lungs
  • Bone e.g. Lead
44
Q

The target organ for toxicity may be the site of accumulation but this is not always the case. True or false?

A

True

45
Q

What is the major site of protein binding?

A

Binding to plasma proteins

46
Q

Examples of plasma proteins

A
  • Albumin
  • α1-Acid glycoprotein
  • Transferrin-a beta globulin- transports Fe
  • Ceruloplasmin, which carries copper

PHA212 - Introductory Toxicology (2 decks)

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