Lecture 2 Flashcards
What is the general cellular response to toxicants?
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
What are some common sources of toxicants?
Pesticides, drugs, home and occupational exposure,poisonous gases, toxins, products of metabolism, photolysis/radiation exposure
What could cause there to be more than one process occurring when looking at response to toxicants?
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)
What is an additive effect?
1+1=2; Sum of individual responses
What is a synergistic effect?
1+1=5; overall response exceeds sum of individual responses
What is a potentiation effect?
0+1=5; similar to synergistic, but two substances may have different effects or only one may be toxic
What is an antagonistic effect?
1+1=0.5; one substance decreases the effect of other
What chemical properties influence toxicity factors?
Solubility, polarity, ionization (pH, valence); lipid/water coefficient affects distribution and availability of compounds
What physical characteristics affect toxicity factors?
Particle size, shape, exposed surface area
How does composition of the toxicant preparation affect toxicity factors?
Homogeneity of the solution (combinations can form insoluble precipitates; mixing/settling of powders and emulsions), impurities, vehicle/inert ingredients/carriers
What about stability/storage can affect toxicity factors?
Breakdown products (can be more or less toxic than parent compound), degradation after mixing of components, exposure to light, humidity, air, etc
What are toxicity factors influenced by?
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
How does ambient air temperature and composition influence toxicity factors?
Increased stress and susceptibility to toxicants at extremes of temperature, change in composition, especially in enclosed environments can be detrimental
How can light patterns influence toxicity factors?
Affect reproductive status/endocrine function, diurnal patterns can affect enzyme activity
How can animal density/noise/pheromones influence toxicity factors?
Stress related to isolation or crowding
How can handling affect toxicity factors?
Stress an precipitate toxicoses such as copper toxicosis in sheep
What is toxicokinetics?
Describes the rate of ADME of xenobiotics within a biological system; used to determine the risk of toxicity associated with ADME
How does absorption occur in the respiratory tract?
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
What affects absorption by the gastrointestinal tract?
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
What affects dermal absorption?
Effective barrier (stratum corneum); primarily lipid soluble compounds; affected by integrity of the keratinized epithelium and the thickness of the dermal/epidermal layer
Chemicals leave the blood and enter tissues at varying rates depend on:
Tissue perfusion/blood flow, ability to traverse the capillary endothelial wall, physiochemical properties of the chemical
What are the overall goals of biotransformation?
Increase water solubility of xenobiotic and decrease toxicity
What factors affect biotransformation?
Old and young animals have decreased hepatic enzyme activity, organ/systemic disease, many pathways are saturable (competition for enzyme systems)
What are the major and minor routes of excretion?
Major: kidney, GI tract, lungs
Minor: tears, sweat, skin exfoliation, milk
What are first order reactions?
Non-saturated system, constant fraction of the total drug that is present is eliminated per unit time
What are zero order reactions?
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
