Lash - Toxicology I Flashcards
Toxicology:
Toxicology: study of harmful effects of chemicals on biological systems.
Toxicokinetics:
Absorption, distribution, metabolism and excretion (ADME) of toxins, toxic doses of therapeutic agents, and their metabolites
Toxicodynamics:
The injurious effects of these substances on vital functions
o A chemical produces toxic effects on a biological system whenever it reaches a critical concentration in the target tissue.
Route of Exposure (4)
Route of Exposure: can influence the response to a given dose
o Ingestion (GI tract) o Inhalation (lungs) o Topical (skin) o IV (generally have the greatest and most rapid effect when administered this way)
Toxicity rating chart for chemicals in general
Practically nontoxic > 15 g/kg More than 1 quart
Slightly toxic 5 - 15 g/kg Between pint and quart
Moderately toxic 0.5 - 5 g/kg Between ounce and
quart
Very toxic 50 - 500 mg/kg Between teaspoonful
and ounce
Extremely toxic 5 - 50 mg/kg Between 7 drops and
teaspoonful
Super toxic < 5 mg/kg A taste (< 7 drops)
Durations of exposure: (3)
(1) Acute exposure- a single exposure or multiple exposures over 24-hr period;
(2) Subacute exposure- multiple exposures over 24-hr to 3 month period;
(3) Chronic exposure- multiple exposures over period of 3 months or more.
Two classes of poisons:
Cumulative: accumulate in body and cause irreversible damage
TOTAL EXPOSURE important
Non-Cumulative: readily cleared by the body and do not cause permanent damage if given in low dose
INDIVIDUAL DOSE important (total dose not important as long as individual doses are small)
Examples: aspirin and acetaminophen
Normal vs. overdose kinetics
Administration of drugs under therapeutic conditions: normally eliminated via FIRST ORDER kinetics
Overdose or poisoning: drugs often eliminated by a ZERO ORDER kinetics
o Rate of elimination independent of drug concentration present
o Occurs due to saturation of some process of elimination scheme (ie. enzymatic conversion)
Zero order rate constant (k) =
Rate independent drug interaction.
Zero order rate constant (k) = (A0-A)/t
Rate of elimination per unit time is determined as the difference between initial concentration and concentration at time x, divided by the time x
Units are mg*hour-1
Plotted as a straight line on plot of concentration vs. time
Dose-dependent elimination of toxins:
First order kinetics can be seen at low doses of drugs/toxins
At higher doses, a mixture of first order and zero order may be seen
At even higher doses, complete saturation may occur and zero order kinetics will predominate
Zero-order rate constant:
k= (Ao-A)/t
Alcohol dehydrogenase metabolism
Alcohol dehydrogenase saturated at relatively low [alcohol]
After ingesting several ounces of alcohol, it is eliminated via a zero-order kinetic process
Important Concept: increasing the dose of a toxin at levels where zero-order elimination is observed can produce a DISPROPORTIONATE increase in the blood level of the toxin
Why? Because rate of toxin degradation does not increase to accommodate.
Aspirin metabolism
Rapidly hydrolyzed to salicylate by plasma esterases
Salicylate –> Salicyluric acid (conjugated to glycine)
Metabolic step changes from first order to zero order above a dose of 1g of aspirin (ie. only takes 3 tablets to saturate system)
How do heavy metals exert toxic effects?
Toxic Effects: exerted by their combination with one or more reactive groups that are essential for physiological function
o Example: amino acid groups that play a critical role in catalysis (binding of metals can lead to inhibition of catalytic activity)
3 types of lead poisoning:
Acute inorganic, chronic inorganic, organic
