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18 Cards in this Set
- Front
- Back
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* Occur at site of first contact w/ toxicant
- Caustic substances of caustic substances - Inhalation of irritant materials |
Local Effects
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-Require absorption and distribution from entry to distant site
-most substances produce these effects |
Systemic Effects
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*Sever acid burn plus kidney damage
*Tetraethyl lead - skin plus CNS effect |
Local and Systemic effects
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What are the 7 things that determine causation
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1. Strength of association of variables
2. Specificity of association 3. Biological gradient in dose/response relationship 4. Biologic or theoretical plausibility 5. Consistency of findings in studies 6. Coherence with established knowledge 7. Temporal sequence |
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* Transfer of a chemical from site of exposure into systemic circulation
* Most toxicants cross epithelial barriers to capillaries by diffusion |
Absorption
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What determines absorption rate?
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The concentration at absorbing surface
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These are related to..?
-rate of exposure -Area of exposed site -Dissolution of chemical -Characteristics of epithelial layer -Lipid solubility |
Absorption rate
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What is the most important influence on absorption?
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Lipid solubility
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Rate of Distribution (rapidity) depend upon ...
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-blood flow
- characteristics of toxicant ( affinity for tissue, partition coefficient) |
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Where do very lipophylic compounds store in the body?
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adipose tissue
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Rapid mobilization of the fat, in which lipophylic coumpounds are stored, can rapidly do what?
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Increase blood concentration
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What chemicals store in bone?
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Lead, Strontium, U, Fluoride
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--- Can displace endogenous compounds
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Binding to plasma proteins
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What are the processes by which administered chemicals are modified by organism through enzymatic reactions?
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*1st objective is to make chemical agents more soluble in water and easier to excrete.
* Decrease lipid solubility, which decreases amount at target *Increase ionization--> Increase excretion--> decrease toxicity |
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Biotransformation can result in reactive metabolite formation
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Bioactivation.
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* Can drastically effect the rate of clearance of compounds
* Can occur at any point during the compound's journey from absorption to excretion |
Biotransformation
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What are the key organs in biotransformation?
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- Liver (large Role)
- Lung, kidney, intestine (medium) -Others (low) |
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What are the 2 biotransformation pathways?
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Phase I- make toxicant more water soluble
Phase 2 - Links with soluble endogenous agent (conjugation) |
