toxicology Flashcards
define toxicology
- the study of adverse effects of xenobiotics
define xenobiotics
- chemicals and drugs that are not normally found in or produced by the body
list 3 major disciples of toxicity
- mechanistic
- descriptive
- regulatory
describe mechanistic toxicology
- cellular, molecular and biochemical effects of xenobiotics w/in dose response
- assess degree of exposure
describe descriptive toxicology
- Uses the results from animal experiments to predict what level of exposure will cause harm to humans
- risk assessment
describe regulatory toxicology
- combines mechanistic and descriptive to establish levels of exposure
describe forensic toxicology
- medical and legal consequences of exposure
- validating analytic performance of tests
describe clinical toxicology
- relationship between xenobiotics and disease states
- emphasis on diagnostic testing
describe environmental toxicology
evaluation of environmental chemical pollutants and their impacts on human health
define toxins
endogenous substance biologically synthesized in living cells or in microorganisms
- toxicant and toxic = not produced in living cell
list most common route of exposure
- ingestion
- inhalation
- transdermal abs
describe ingestion exposure
- must be absorbed into circulation by GI
- most passively diffuse
define dose-response relationship
correlates a single, acute oral dose range with the probability of a lethal outcome in an average 154 pound man
define therapeutic index
ratio of TD50 or LD50 to the ED50
define quantal dose-relationship
describe the changes in health effects of a defines population based on the exposure to the xenobiotic
define acute toxicity
usually short term exposure to a substance in which the dose is sufficient to cause immediate toxic effects
define chronic toxicity
generally associated w/ repeated frequent exposure for extended period of time at doses that are insufficient to cause an immediate acute response
- affects different systems than acute
list common specimen types
bloor or urine
what tube top is used for analysis of toxic agents for trace elements
royal blue top (trace element free)
what tube top is used for lead testing
tan top
list and describe steps of toxic agent analysis
- screening: rapid, simple, qualitative intended to detect presence of substances -> sensitive but lack specificity
- confirmatory: quantitative, report concentration of a substance (high specificity and sensitivity)
common methods used in screening and confirmatory test
- immunoassays (drug screen)
- gas chromatography with mass spectrometry
- liquid chromatograph with tandem mass spec (LC-MS)
- inorganic compounds use ICP-MS and AA
alcohol metabolism pathway
alcohol -(ADH)-> aldehyde -(ALDH)-> acid
describe effects of ethanol
- accumulation of lipids in hepatocytes - 20% develop toxic hepatitis, cirrhosis is common
list common indicators of ethanol abuse
- liver markers: GGT, ALT, AST, HDL
describe ethanol metabolic pathway
ethanol -> acetaldehyde -> acetate -> acetaldehyde adducts
describe methanol
- common lab solvent
- accidental ingestion from homemade alcohol
- formic acid final metabolite causes metabolic acidosis
describe isopropanol
- rubbing alcohol
- metabolized by hepatic ADH to acetone
- CNS depressant
- can have severe acute like response over long time
describe ethylene glycol
- immediate effects similar to ethanol
- in antifreeze
- calcium oxalate crystals damage renal tubules
how is alcohol determined
- serum, whole blood, plasma
- ethanol is uniform in body water = use serum
- osmo, chromatographic, enzymatic (non human ADH to NADH)
what is the established reference method for alcohol determination
headspace GC coupled with flame ionization
describe carbon monoxide
- produced by incomplete combustion of carbon substances
- makes carboxyhemoglobin
- treatment w/ 100% O2
describe cyanide
- inhalation, ingestion, skin abs
- used in industrial processes, insecticides and rodenticides
- cleared by kidneys
- binds heme iron
describe arsenic
- natural and manmade
- 3 main groups (gas, inorganic, organic)
- rate of abs depends on form
describe cadmium
- significant environmental pollutant (taken up by crops and tobacco)
- toxic to kidneys
- concomitant parathyroid dysfunction and vitamin D def
- itai-itai disease and cadmium rice
describe lead
- found mostly in bone and soft tissue (long half life)
- renal elimination
- dose dependent toxicity
- abdominal or neurological symptoms after ACUTE exposure
what does lead inhibit
- enzymes
- specifically vitamin D metabolism and heme synthesis
describe mercury
- 3 forms
- contaminated food source (more common) or accidental ingestion
- binds w/ proteins
describe salicylates(aspirin)
- can cause excess ketone formation
- interferes w/ plt aggregation and GI function
- high dose metabolic acidosis
- chromogenic assay = trinder reaction
describe acetaminophen
- tylenol
- hepatotoxicity at low doses
- low free fraction
confirmation testing must use what levels of specificity and sensitivity
high and high but different methods
what is the most common refernce method of DOA confirmation testing
gas chromatograph - mass spec
describe amphetamines
- hypertension overdose but rar
- urinalysis
describe sedative - hypnotics
- CNS depressant
- barbiturates and benzodiazepines most common
-> barbit: higher abuse potential
-> benzo: more commonly found
describe barbiturates
- high abuse potential
- sleep inducer
- phenobarbital
describe benzodiazepines
- CNS depressant
- used for anti-anxiety meds
- metabolites found in urine
describe THC
- THC is a lipophilic substance and removed from circulation by passive diffusion
describe cocaine
- CNS stimulator
- alkaloid salt
describe opioids
- chemically related to opium poppy
- acute overdose = respiratory acidosis
describe TCA overdose
- block reabsorption of serotonin and norepinephrine
describe MDMA
- amphetamine derivative ‘ecstasy’
- GC-MS or LC-MS
describe PCP
- angel dust
- lipophilic drug into fat and brain
describe anabolic steroids
- toxic hepatitis
- can cause enlargement of heart
