Exam 1: Toxicokinetics

Question 1

What physiologic factors differentiate the stomach vs. the small intestine in terms of ability to absorb toxicants?

Answer 1

Stomach: secretion and movement [increases solubility, breaks down acid labile compounds]
Small intestine: absorption (larger surface area)

Question 1

What factors effect the passage of toxicants across biological membranes?

Answer 1

Concentration gradient across the membrane
Surface area of the membrane
Toxicant permeability
Macromolecule binding

Question 2

What role does the liver play in the oral bioavailability of toxicants?

Answer 2

Compounds that are rapidly absorbed and efficiently metabolized aren’t going to enter systemic circulation
The liver is more susceptible to orally delivered toxins
Enterohepatic circulation increased intestinal exposure

Question 3

What factors play a role in the dermal absorption of toxicants?

Answer 3

Surface area
Permeability
Perfusion

Question 4

Would a water-soluble toxicant be expected to cross through the skin?

Answer 4

No, lipophilic to cross stratum corneum
Hydrophilic enough to go into the more aqueous dermal layer only

Question 5

Perfusion Limited Distribution

Answer 5

Drug distribution to tissues is equal to the amount of blood flow that each tissue receives

Question 6

Diffusion Limited Distribution

Answer 6

Occurs when the rate-limiting factor for distribution is the movement of drug from the blood to the tissue
Happens primarily with drugs crossing tightly knit membranes
Main dictating properties: lipid to water partitioning, degree of ionization

Question 7

What role can metabolism play in species differences in the toxicity of a toxicant?

Answer 7

Different species have different metabolic capabilities - differ in rate of metabolism and metabolites formed

Question 8

Does metabolism always involve the disappearance of a toxicant? What other role can metabolism play in toxicant exposure?

Answer 8

In general, metabolism is a detoxification process, but metabolic activation may be required for a compound to exert a toxic effect
Metabolites can be active, toxic, inactive, non-toxic

Question 9

How are toxicants eliminated from the body?

Answer 9

Urine
Feces
Sweat
Saliva
Milk
Exhalation

Question 10

What role does the liver play in elimination?

Answer 10

Primary role is liver biotransformation reactions and transfer of compounds into the bile via active transport
Factors: blood flow, enzymatic activity, protein binding
Compounds with high liver extraction have poor oral bioavailability

Question 11

What role does the kidney play in elimination?

Answer 11

Filtration + active secretion - reabsorption

Question 12

What are the three factors involved in renal elimination and what factors influence how dominant a role they play in renal elimination?

Answer 12

Filtration = blood flow, protein binding
Active secretion = proximal tubule
Reabsoprtion = permeability

Question 13

Be able to estimate the bioavailability of a toxicant given appropriate AUC data from various routes and doses of administration.

Answer 13

Question 14

Be able to describe how the terminal half-life of a toxicant can influence the treatment of a poisoned animal.

Answer 14