Lecture 2

Question 0

What is the general cellular response to toxicants?

Answer 0

Alter membrane integrity, abnormal accumulation of cellular lipids and pigments, altered energy metabolism, affect protein/macromolecular synthesis and function, alter cell growth patterns, cell death

Question 1

What are some common sources of toxicants?

Answer 1

Pesticides, drugs, home and occupational exposure,poisonous gases, toxins, products of metabolism, photolysis/radiation exposure

Question 2

What could cause there to be more than one process occurring when looking at response to toxicants?

Answer 2

Interaction between prescribed drugs, ingestion of two or more toxicants, ingestion of a toxicant while on a therapeutic drug, enhanced delivery systems (vehicle, dispersants, humectants, inert ingredients)

Question 3

What is an additive effect?

Answer 3

1+1=2; Sum of individual responses

Question 4

What is a synergistic effect?

Answer 4

1+1=5; overall response exceeds sum of individual responses

Question 5

What is a potentiation effect?

Answer 5

0+1=5; similar to synergistic, but two substances may have different effects or only one may be toxic

Question 6

What is an antagonistic effect?

Answer 6

1+1=0.5; one substance decreases the effect of other

Question 7

What chemical properties influence toxicity factors?

Answer 7

Solubility, polarity, ionization (pH, valence); lipid/water coefficient affects distribution and availability of compounds

Question 8

What physical characteristics affect toxicity factors?

Answer 8

Particle size, shape, exposed surface area

Question 9

How does composition of the toxicant preparation affect toxicity factors?

Answer 9

Homogeneity of the solution (combinations can form insoluble precipitates; mixing/settling of powders and emulsions), impurities, vehicle/inert ingredients/carriers

Question 10

What about stability/storage can affect toxicity factors?

Answer 10

Breakdown products (can be more or less toxic than parent compound), degradation after mixing of components, exposure to light, humidity, air, etc

Question 11

What are toxicity factors influenced by?

Answer 11

Health status, age; metabolic activity; energy/nutritional state, gender and hormonal differences, specific species, strain/breed variation, localization in tissues with little PI/PII activity or low or high oxidative potential, immune status, idiosyncratic reactions, status of CNS, disease or debilitation

Question 12

How does ambient air temperature and composition influence toxicity factors?

Answer 12

Increased stress and susceptibility to toxicants at extremes of temperature, change in composition, especially in enclosed environments can be detrimental

Question 13

How can light patterns influence toxicity factors?

Answer 13

Affect reproductive status/endocrine function, diurnal patterns can affect enzyme activity

Question 14

How can animal density/noise/pheromones influence toxicity factors?

Answer 14

Stress related to isolation or crowding

Question 15

How can handling affect toxicity factors?

Answer 15

Stress an precipitate toxicoses such as copper toxicosis in sheep

Question 16

What is toxicokinetics?

Answer 16

Describes the rate of ADME of xenobiotics within a biological system; used to determine the risk of toxicity associated with ADME

Question 17

How does absorption occur in the respiratory tract?

Answer 17

Ionizable compounds absorb rapidly across alveoli by passive diffusion (metals) and don’t accumulate in the lungs; gases can be corrosive, a simple asphyxiant or have systemic effects; deposition affected by host influences (anatomy, rr, etc) and particle size

Question 18

What affects absorption by the gastrointestinal tract?

Answer 18

Intestinal blood flow, GI motility, changes in stomach emptying time, gastric pH, intestinal pH, biotransformation, permeability of gut wall, bile secretion, entero-hepatic circulation, digestive enzyme/mucus secretion, alteration of normal GI flora

Question 19

What affects dermal absorption?

Answer 19

Effective barrier (stratum corneum); primarily lipid soluble compounds; affected by integrity of the keratinized epithelium and the thickness of the dermal/epidermal layer

Question 20

Chemicals leave the blood and enter tissues at varying rates depend on:

Answer 20

Tissue perfusion/blood flow, ability to traverse the capillary endothelial wall, physiochemical properties of the chemical

Question 21

What are the overall goals of biotransformation?

Answer 21

Increase water solubility of xenobiotic and decrease toxicity

Question 22

What factors affect biotransformation?

Answer 22

Old and young animals have decreased hepatic enzyme activity, organ/systemic disease, many pathways are saturable (competition for enzyme systems)

Question 23

What are the major and minor routes of excretion?

Answer 23

Major: kidney, GI tract, lungs

Minor: tears, sweat, skin exfoliation, milk

Question 24

What are first order reactions?

Answer 24

Non-saturated system, constant fraction of the total drug that is present is eliminated per unit time

Question 25

What are zero order reactions?

Answer 25

Saturated system; constant amount of drug is eliminated per unit time

Drugs may obey zero order kinetics at high concentrations and first order at low concentrations