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17. Toxicology- Dr. Campbell- PBT4
Terms in this set (43)
Definition: the study of adverse effects of chemicals on living organisms
T/F: Side effects of therapeutic drugs may be desirable or toxic
If a drug has an effect that is NEVER desirable, it is referred to as _____ effects of the drug.
What is the toxic effect of thalidomide?
Teratogenic effects (birth defects)
EXPOSURE VS ADMINISTRATION:
-In pharmacology, the major routs by which drugs are ____ include injections, inhalation, ingestion and dermal absorption.
- In toxicology, we refer to entry of chemicals as routes of ___. These include: ingestion (GI tract), inhalation (lungs), intravenous (blood stream), topical/dermal (skin)
- Toxic agents produce the most rapid and greatest response via which route?
- intravenous (bloodstream)
Define: Amount of toxicant administered and the degree of biological response are so well correlated that this relationship is considered the most fundamental concept of toxicology.
____ is a dose-response relationship in a population, involving "all or none" effects.
Definition: In toxicology, this is used to determine the lethal dose in 50% (LD50) of the experimental test animals for new chemicals.
Definition: an abnormal response to a chemical which is genetically determined. Identified as extreme sensitivity to low doses or abnormal insensitivity to high doses of the chemical
The shape of a dose response curve depends on the response measured. For individual dose-response relationships for an essential nutrient, such as vitamins and minerals, the shape of the response curve is ____.
Definition: the concept that some non-nutritional toxic chemicals may have beneficial properties at low doses. Ex. radiation effects.
Definition: the comparison of the therapeutically effective dose with the toxic dose of a drug.
- What is the equation for therapeutic index?
- What is the equation for Margin of Safety?
- TI= LD50/ED50 (therapeutic index= Lethal Dose 50% of population/ effective dose of 50% of population)
- Margin of Safety= LD1/ED99
T/F: The smaller the ratio for therapeutic index, the safer the drug.
F. the larger the ratio
The margin of safety is LD___/ED___.
NOAEL stands for ____.
no observable adverse effect level
- Routes of exposure to toxicants include: ____, ____, ____, and ___.
inhalation, ingestion, dermal absorption, intravenous exposure
____ is the most important concept in toxicology. Paracelsus stated that the ___ differentiates a poison from a remedy.
Dose response relationships are in the form of: _____ (graded) and ____ (population response)
Chemical idiosyncrasy is due to _____.
For essential nutrients, the dose response curve is different. It is ____. Both ___ and ___ will cause adverse effect.
U-shaped; deficiency; toxicity
____ and ____ will determine degree of toxic response.
Frequency of exposure; elimination rate
_____ depends on how a toxicant enters an organism, the way by which it interacts with target molecules, and how the organism handles the toxic insult
Mechanism of toxicity
What are the 4 steps underlying the mechanism of toxicity?
1. Delivery to target
2. Reaction of ultimate toxicant to the target molecule
3. Cellular Dysfunction
4. Repair or Dysrepair
STEP 1: Delivery to Target
The toxic response depends on the ____ and ___ of the ultimate toxicant.
Example of Repair/dysrepair: Mitochondrial insult
- in a few mitochondria, result:
-in more mitochondria, result:
- in all mitochondria, result:
- necrosis (killing of most/all cells of an organ)
Definition: a toxicant produces injury to only one kind of cellular form without harming another living matter although the two may exist in close contact. Ex. Antibiotics kill bacteria but do not harm us.
Selectivity is caused by different phenomena:
- Chemical causes toxicity to both ___ forms but is only accumulated by ___ tissue. Ex. ___ is selectively accumulated in thyroid.
- Toxicant reacts with a biological feature which is only present in the ____ form. Ex. ___ component of bacteria allows for selective destruction.
-cellular; sensitive; Iodine
- sensitive life; cell wall
Individual differences are do to ___ in the population.
Mechanism of toxicity depends on what 4 things?
1. delivery of toxic agent to target molecule
2. Interaction of toxicant w/ target molecule
3. cellular injury due to interaction of toxic agent with target molecule
4. Failure of repair mechanisms.
The ultimate toxicant may be: ___ compound, ____ of the parent compound, or a(n) ___ compound.
-parent; metabolite; endogenous
___ occurs due to accumulation dynamics of unique biological characteristics. Individual differences are due to ____.
Selective toxicity; genetic polymorphisms
What are the 6 steps that are necessary for optimal care of a poisoned patient that are taken by clinical toxicologists?
1. stabilize patient
2. clinical evaluation
3. prevent further absorption
4. enhance of elimination
5. admin of antidote
6. supportive care/clinical follow up
- Thorough examination needed to assess ___ and possible ___.
mental status; trauma.
What are the 3 methods to prevent further toxicant absorption via ingestion?
induction of emesis, gastric lavage, activated charcoal.
Currently ___ is the only agent used for emesis (for induction of vomiting).
syrup of ipecac
Definition: an orogastric tube is placed in the stomach and fluid is aspirated. Less commonly used bc of risk of aspiration and limited effectiveness. Only effective in patients who have had recent oral exposure.
What are the 3 methods that allow for enhancement of elimination?
-alkalinization of the urine
- Multiple-dose activated charcoal (MDAC)
Alkalinization of the urine:
- ____ renal clearance of weak acids.
- ___ due to increase pH prevents reabsorption.
- Acidification is NOT recommended due to ____.
- Ion trapping
- adverse effects
Definition: This method of enhancement of elimination is efficient only if toxic agent has low volume of distribution, low protein binding, high water solubility, and low molecular weight.
Multiple-dose Activated charcoal: Increases systemic clearance of various drugs via ____ from blood to charcoal passing through GI tract.
Supportive care and follow-up:
-Close vigilance is necessary because patients may be effected by ____ or ___.
nosocomial infections; pneumonitis
Step-wise treatment of Poisoned patients:
- STABILIZATION OF THE PATIENT: make sure ___, ___, and ___ are intact.
-CLINICAL EVALUATION: history- type of ___ and ___ of exposure. Physical exam- evaluate ___ and ___. Laboratory evaluation- rapid assays limited.
- PREVENTION OF FURTHER GI ABSORPTION OF TOXIC AGENT: ___-induces vomiting within 30 min. ____- less commonly used due to risk of aspiration. ____- has high binding capacity for organic molecules. Not as effective for ___ substance or ____ salts.
- ENHANCEMENT OF ELIMINATION: ____- increases renal clearance by "ion trapping". ___- effective if toxicant has low volume of distribution, low protein binding, high water solubility, low molecular weight. ____- increases systemic clearance via transluminal efflux.
- USE OF ANTIDOTES: limited number are available. These may be ____, drugs which antagonize activity of toxin, or drugs which antagonize interaction of toxin with target site.
- SUPPORTIVE CARE AND FOLLOW UP: ___ is recommended for unstable patients. ____ consults are necessary for attempted suicides.
- vital signs, respiration, and circulation.
- toxicant; time; mental status; gag reflex
- syrup of ipecac; gastric lavage; activated charcoal; low molecular weight; small inorganic
- Urinary alkalinization; Dialysis; MDAC
- Chelating agents
- ICU; psychiatric.
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