Study Set Content:
The likelihood of a toxic response to be reversed largely depends on the ability of an injured tissue to adapt, repair, and regenerate. However, there are limits to this repair capacity, and very high doses may () this adaptive response to permanent loss of function and potentially fatal liver failure.
overwhelm
occur at the site of first contact.
Local Toxicity
is the general site of action and it requires absorption and distribution.
Systemic Toxicity
Target organs in order of frequency are the
CNS; the circulatory system; the blood and hematopoietic system; visceral organs such as the liver, kidney, and lung; and the skin.
are seldom target tissues
Muscle and bone
Occurs when the combined responses of two chemicals is equal to the sum of the responses to each chemical given alone.
Additive
Observed when the combined responses of two chemicals are much greater than the sum of the response to each chemical when given alone.
Synergistic
Occurs when one substance does not produce any toxicity on a particular tissue or system but when added to another chemical makes that chemical much more toxic.
Potentiation
Occurs when two chemicals administered together interfere with each other’s actions or one interferes with the action of the other.
Antagonism:
occurs when two chemicals that bind to the same receptor produce less of an effect when given together relative to the addition of their separate effects (e.g., 4 + 6 = 8) or when one chemical antagonizes the effect of the second chemical (e.g., 0 + 4 = 1). Receptor antagonists are often termed blockers.
Receptor antagonism
a direct chemical reaction between two compounds that produces a less toxic product. For example, chelators of metal ions decrease metal toxicity and antitoxins antagonize the action of various animal toxins.
Chemical antagonism or Inactivation
occurs when the absorption, distribution, biotransformation, or excretion of a chemical is altered such that the concentration and/or duration of the chemical at the target organ is reduced.
Dispositional antagonism
occurs when two chemicals counterbalance each other by producing opposing effects on the same physiological function
Functional antagonism
Receptor
Chemical
Dispositional
Functional
a state of decreased responsiveness to a toxic effect of a chemical resulting from prior exposure to that chemical or to a structurally related chemical.
Cross-Tolerance
there is a decreased amount of toxicant reaching the target site.
Dispositional tolerance
may result from a lower availability of receptors and/or mediators (e.g., neurotransmitters). Characterist
Chemical or cellular tolerance
