Toxicology 2 Flashcards
If you wanted to try to prevent absorption of an orally ingested poison, which is the best choice of treatment? A. Emesis B. Gastric lavage C. Activated charcoal D. Catharsis
C. Activated charcoal (usually hydrophobic compounds and should be given within 3 hours of ingestion)
What is the risky part about using emesis, gatric lavage, or activated charcoal?
aspiration
What is the risk for catharsis?
ruptured of GI tract
What is gastric lavage?
They put a slurry in your stomach and suck it out with a big boar tube.
Methanol poisoning is treated:
A. By inhibiting alcohol dehydrogenase
B. With the administration of ethylene glycol
C. By inhibiting aldehyde dehydrogenase
D. With the administration of oxalic acid
A. By inhibiting alcohol dehydrogenase
with ethanol
Stopping bioactivation is pharmacokinetics or pharmacodynamics?
pharmacokinetics (stopping or inhibiting metabolism)
What type of treatments are pharmacodynamics?
bypassing inhibited pathway
receptor antagonist
receptor agonist
pulling a poison from an active sites
What are the three basic approaches to treating a poisoned patient?
Toxicokinetic based
Inactivation of poison
Pharmacologically based
What are the different toxic endpoints?
On and off target effects Non-organ specific toxicity Organ specific toxicity Idiosyncratic responses Allergic Reaction
What organs are highly susceptible to toxicity?
Liver, kidney, nervous system, and lungs
A compound with a half life that allows it to be cleared from the body before the next exposure can result in chronic adverse effects. How can that happen?
A multiple exposure where tissue damage can not be repaired before the next exposure.
Which of the following is considered an area of specialty practice in the field of toxicology?
Clinical Toxicologist
What is the spectrum of undesired effects?
Immediate vs Delayed Reversible vs Irreversible Local vs Systemic Interactions Tolerance Variations in Response
What is an immediate response?
Those that occur rapidly after a single administration of a substance.
What is a delayed effect?
Those that occur after the lapse of some time after administration of a substance.
What are extreme examples of delayed effects?
Diethylstilbestrol (DES) and vaginal cancer - Generational delayed effect. Prescribed hormone used in the 50s for woman to hold on to pregnancy. Causes baby girls to develop cancer later in life and for boys to have problems with urinary tract.
Triorthocresylphosphate (TOCP) and neurotoxicity - organophosphate that binds to another enzyme Neuropathy Target Esterase (NTE) and inhibits it. You get tingly get lots of sensation a few days later. Expect SLUDE but this happens later.
Some toxic effects are reversible and others are irreversible. T/F
True
What determines if a toxic effect is reversible or irreversible?
The ability of a tissue to regenerate or not.
Most injuries in the liver are irreversible or reversible?
Reversible due to the livers high ability to regenerate.
Most injuries in the differentiated cells in the CNS are irreversible or reversible?
Irreversible due to the fact that the cells of the CNS cannot dived and be replaced.
Cancer and birth defects are considered irreversible or reversible toxic effects?
Irreversible
Where do local effects occur?
At site of first contact.
What are some examples of local effects?
Chlorine Gas - damages peoples lungs, eyes, skin.
Poison Oak - damages skin
Reactive Acids - because they are reactive
Where do systemic effects occur?
Require absorption at site of entry and distribution to site of action.
What are examples of systemic effects?
Most toxins unless they are highly reactive.
What poisons may have both local and systemic effects?
Tetraethyl lead - burns skin and can cause CNS damage
What poisons can cause indirect systemic effects?
Acid burns, Chlorine burns - you damage the skin so much that you cause problems in renal function due to fluid loss. Kidney failure
Interactions of different compounds that we are exposed to can do what?
Change the kinetics of it: absorption, protein binding, biotransformation and excretion of one or both interacting compounds.
What responses can you have when you have multiple chemical reactions?
Additive - add the effects
Synergistic - Sum of the effects is greater than each compound alone.
Potentiation - One chemical not toxic in itself will enhance the effects of another toxin.
Antagonism - Sum of the effects is less than what was expected
What is tolerance?
A decreased responsiveness to a toxic effect resulting from prior exposure to a chemical or a structurally related compound.
What are two major mechanisms for tolerance?
Dispositional tolerance: decreased amount of toxicant reaching site where toxic effect is produced.
Reduced responsiveness of tissue to a compound.
What is an example of dispositional tolerance?
Carbon tetrachloride - induces some of the enzymes metabolize it and help you clear it.
Cadmium 3 - induces expression of a carrier protein, metalathionine, will grab on to the metal and help increase the clearance for it.
What is an example of reduced responsiveness?
pharmacodynamics. Opioid down regulation.
What is selective toxicity?
lethal to one species but not to another
What is an example of selective toxicity?
chocolate and dogs
Insecticides on the crops - kills off bugs but not plants
Why are there variations in toxic responses?
Selective Toxicity
Species differences
Individual Differences in Response
What is species differences?
One species is not affected to the same quantity or quality as another species. This raises questions of extrapolation of results between species like mice. Have to use the right animal
Why do individuals differ in their response?
Genetic differences, and possibly what we eat and our lifestyle
If different organs are being effected than the ______ is likely different.
Mechanism of Action
Toxic exposures may cause specific organ and non-specific physiological endpoints. T/F
True
Toxic exposures may see multiple specific organs and/or non-specific physiological responses for any given exposure. T/F
True
Why are there adverse effects when a drug hits an intended tissue on-target?
The dose is too high
Chronic activation of inhibition effects
Why are there adverse effects when a drug hits an intended tissue off-target?
Incorrect receptor is activated or inhibited
Why are there adverse effects when a drug hits an unintended tissue on-target?
Correct receptor, but incorrect tissue
Dose too high
Chronic activation or inhibition effects
Why are there adverse effects when a drug hits an unintended tissue off-target?
Incorrect receptor is activated or inhibited
What can cause a dose at the receptor to be too high?
Deliberate or accidental dosing errors.
Changes in pharmacokinetics of drug.
Change in receptor number
Changes in pKA