E3-Toxicology/HeavyMetals(Powerman5000) Flashcards
Defined as the range of response per dose
An individual may require a higher/lower dose to produce the desired effect
Biological Variation
Response of the patient to the drug is QUALITATIVELY different from the usual or expected response
drug idiocycracy
Geriatrics- Give (lower/higher)? dose
lower
A rapid development of tolerance…example?
TachYphylaxis-local anethesia
Dose of a drug that kills 50% of the total numbers of mice that received it
Lethal Dose (LD)
Dose of a drug that causes an effect in 50% of the total numbers of mice that received it
Effective Dose (ED)
Margin of safety = ?/?….Acceptable margin of safety is _____ or more
LD50/ED50… 2000
Also known as chronic toxicity studies
Daily dosing to rats and dogs from 3 months
to 2 years
Observe for toxicities, evaluate blood chemistries
Sacrificed, then evaluate histopathology
Many toxic effects appear only after repeated dosing over many months or years
long term toxicology
Theraputic Index = ?/?
TD50 (toxic) /ED50 (effective)
Study of the absorption, distribution, metabolism and excretion of toxic parent compounds and metabolic products
Used to predict the concentration of toxin that reaches the site of injury and the resulting damage
Toxicokinetics
There are 3 primary sites of absorption into the body:
– Gastrointestinal tract – Respiratory tract
– Skin
Rate of distribution to a particular tissue is related to the amount of ______ to the tissue
blood flow
Concentration of the toxin in each tissue is determined by the ______ of the toxin for the tissue
affinity
Cross cell membranes
– _____ soluble cross directly
– ______ soluble = cross through channels/pores through receptor-mediated mechanisms
Lipid…… Water
Toxins that are _____-soluble molecules (polar) have difficulty crossing the blood brain barrier
water
Occurs primarily in the _____ Process is called = detoxication….Nontoxic materials may be converted into toxic metabolites after undergoing metabolism in the _____
Process is called = toxication
liver…liver
In summary, toxins can undergo 3 types of changes with metabolism (just like drugs):
(active to inactive)…(inactive to active)…(active to active)
Renal excretion of _____-soluble molecules
water
Lead = stored in _____ for decades following exposure
bones
DDE = a metabolite of the pesticide DDT stored for years in ____
FAT
Inhaled particulates = phagocytosed (engulfed) by macrophages, but may never be eliminated
– Found in _____ and _______ at autopsy
lung and lymph nodes
Reactive Species - Example __________
– Solvent used in cleaning products and in
fire extinguishers
– Not hepatotoxic in itself
– When metabolized by the liver, reacts with oxygen to form toxic organic free radicals
– These free radicals cause toxicity (renal toxicity, hepatotoxicity, liver cancer)
Carbon tetrachloride
Nerve gases and pesticides are _________________
inhibitors
acetylcholinesterase
______ binds to the heme iron in the active site of the enzyme cytochrome C oxidase; inhibition of this enzyme prevents the generation of ATP
CN-
Receptor-Mediated
– ________ binds strongly to the iron in the active site of hemoglobin, preventing oxygen binding and reducing oxygen carrying capacity
Carbon monoxide
Carcinogen = a chemical, physical or biological substance that can cause _________
transformation
Most teratogens are ________ or ________
reactive species or metabolic inhibitors
What is ________ toxicity?
Examples:
– Targeting a protein that is unique to the
pathogen’s survival
selective
Antifungal drugs are not good at ________ targeting
selective
Everyone has about ___ micrograms of arsenic in body daily, but can tolerate it well
3
“garlic breath” = able to diagnose this poisoning due to smell
arsenic
Used for semiconductor manufacturing, increases hardness of lead, batteries, soldering materials, matches…. Used for the treatment of protozoan infections
antimony
Samsung places in washing machine for
antibacterial effect on clothing…Kohler has _____ ions in new toilet seats….FDA approved endotracheal tube coated with ______ to prevent ventilator-associated pneumonia (VAP)
silver
Bluish-grayish pigmentation of skin and mucous membranes (Smurf looking dude)
Argyria (silver tox)
Pure gold is not _____
toxic
Gold ____ are toxic to liver and kidneys
salts
In 1800s, was in teething powders for infants and to treat toothaches
Merc
With continuing exposure, a fine tremor develops and may escalate to violent muscular spasms. Tremor initially involves the hands and later spreads to the eyelids, lips, and tongue.
Merc
________ mercury = corrosive to oral cavity and gut
– Used in dental amalgam – Kidney damage
INORGANIC
Enzyme inhibitor in the production of heme
– Inhibits protoporphyrin IX; accumulation of aminolevulonic acid = diagnostic
Lead
______ lines are visible in teeth in children – Dark line (gray) along gingiva
Lead
Antidotes: combination calcium EDTA and dimercaprol..Combination better than either agent alone
Lead
Historial uses: treatment of enlarged joints and glands
Known to cause cancer
Cadmium
Similar to lead poisoning; inhibits same processes as lead
Cadmium
Complexes with trivalent ions (Ferric ions) to form ferrioxamine, which is removed by the kidneys
deferoxamine
“pots and pans” senility
Concern for association with Alzheimer’s disease (little to no evidence)
Aluminum
Exposure from electronic, steel and mining industries
Symptoms: dermatitis, nasal and respiratory cancer
Nickel
Really the only slide that matters: Antidote?
– Arsenic, antimony, gold, mercury
Dimercaprol
Really the only slide that matters: Antidote? Lead, cadmium
Calcium disodium edetate (EDTA)
Really the only slide that matters: Antidote? Gold, mercury
Penicillamine
Really the only slide that matters: Antidote? Iron and aluminum
Deferoxamine
Really the only slide that matters: metal(s)? Dimercaprol (4)
Arsenic, antimony, gold, mercury
Really the only slide that matters: metal(s)? Calcium disodium edetate (EDTA) (2)
Lead, cadmium
Really the only slide that matters: metal(s)? Penicillamine (@)
Gold, mercury
Really the only slide that matters: metal(s)? (2)
Iron and aluminum
