Clinical Chemistry: Toxicology Flashcards
toxicology
the study of adverse effects of xenobiotics in humans
xenobiotics
chemicals and drugs not normally found or produced in the body; exogenous agents that may have adverse effects on a living organism; environmental or drug exposures; medications
poisons
have an adverse effect on biological system; used when describing animal, plant, mineral, or gas; arsenic, lead, CO, poison ivy
toxins
substances that are biologically synthesized in living cells or microorganisms; bacteria, mycobacterium, S. aureus, snakes
mechanistic
cellular and biochemical effects of toxins; context of dose-response relationship
descriptive
uses results of animal experiments to predict what level of exposure will cause harm in humans; risk assessment
regulatory
used data from mechanistic and descriptive to establish standards regarding acceptable levels of exposure; oversees human safety issues associated with therapeutic drugs, cosmetics, and food additives
forensic
primarily medical and legal consequences of chemical or drug exposure
suicide attempts
50% of poisoning cases
accidental exposure
30% of poisoning cases
ingestion, inhalation, and transdermal absorption
three exposure routes
pH, rate of dissolution, gastric motility, resistance to degradation in GI tract
factors affecting absorption
effective dose
dosage determined to be effective in 50% of the population
toxic dose
dosage determined to be toxic to 50% of the population
lethal dose
dosage determined to be lethal to 50% of the population
interfere with enzyme actions and systems, block oxygen usage and transport, interfere with cell function, and cause hypersensitivity
four mechanisms of toxicity
screening tests
rapid, simple, qualitative procedure to detect specific substances or classes of toxicants; good analytic sensitivity, but lack specificity
confirmatory testing
immunoassays, TLC, and GC/MS
alcohol
CNS depressant (changes membrane properties) causing disorientation, confusion, and euphoria; unconsciousness, paralysis, and death at high concentrations; changes in membrane properties to exert immediate effect
alcohol -> aldehyde -> acid (ADH + ALDH)
biotransformation of alcohols
ethanol
most commonly consumed alcohol; long term health effects include alcoholic hepatitis and cirrhosis, lipid deposition in the liver
EtOH -> Acetaldehyde -> Acetate -> Acetaldehyde adducts
ethanol mechanism
acetaldehyde adducts
EtOH product that changes structure and function of proteins in the body
cirrhosis
fibrosis in liver affecting hepatic funciton
AST/ALT ratio >2.0
highly specific for ethanol-related liver disease
increased MCV
hematology impact due to EtOH consumption
high serum HDL
impact on lipid panel caused by EtOH consumption
GGT
...
AST
...
methanol MeOH
common solvent used as cleaning solution and a liquor contaminant; leads to severe acidosis and blindness; converted into formaldehyde and formic acid leading to death
isopropanol
converted into acetone which has a longer half life and longer affects than EtOH; similar effects to ethanol
ethylene glycol
ingestion leads to toxic byproducts (oxalic and glycolic acid) and crystal deposits (calcium oxalate) in tubules causing severe metabolic acidosis and renal tubular damage
alcohol testing method
uses gas chromatography; enzymatic methods using ADH and measurement of NADH-specific for EtOH
carbon monoxide
a colorless, odorless, tasteless gas rapidly absorbed into blood from inspired air; considered highly toxic due to its affinity for and binding to hemoglobin, displacing oxygen; produced by incomplete combustion of carbon-containing substances of primary environmental sources: gasoline engines, improperly vented furnaces, and wood or plastic fires; symptoms: SOB (without strenuous exercise), severe headaches, fatigue, impaired judgment
differential spectrophotometry
used to measure carboxyhemoglobin against regular hemoglobin since different forms of hemoglobin (hgb, A1c, CoHb) absorb at different wavelengths
0.5
CoHb of healthy adult
5-15
CoHb of smoker
40-50
CoHb leading to confusion and fainting
60-70
CoHb leading to unconsciousness
80
CoHb that is immediately fatal
gas chromatography
reference method for carboxyhemoglobin measurement since it is accurate and precise
pulmonary edema, shock, death
toxicology of aspiration
perforations in esophagus and GI tract
toxicology of ingestion
rapid development of metabolic acidosis or alkalosis
risk of caustic agents
cyanide
found in industrial processes, insecticides, rodenticides; produced by burning of some plastics; common suicide agent; associated with fires and smoke inhalation; binds heme, decreasing oxygen, depleting ATP; increases in cellular oxygen tension and venous pO2 occur as a result of lack of oxygen utilization causing headaches, dizziness, respiratory depression, leading to seizure, coma, and death
binding to heme iron, uncoupling oxidative phosphorylation and depleting ATP
how cyanide expresses toxicity
ISE and photometric
techniques used to measure cyanide
thiocynate
can be measured in urine for low level exposures to cyanide
arsenic
exists in both naturally occurring and manmade substances; binds to proteins affecting function; measured with AAS; short time in blood so urine is specimen of choice-90% in 6 days
cadmium
electroplating and galvanizing; mining and processing of many other metals; environmental pollutant found in tobacco shellfish and vegetables; binds to proteins with major effects on the renal system; AAS in whole blood or urine
lead
common constituent of household paints before 1972; byproduct of many industrial processes; plumbing materials; slow elimination so it builds up in the body over time; children very sensitive; measurement chromogenic-AAS
abdominal and neurological impact, cerebral edema and ischemia
acute exposure to lead impacts
behavioral changes, hyperactivity, ADD, IQ
subclinical exposure to lead impacts
vitamin D metabolism and heme synthetic pathway
key impacts of lead exposure on enzymatic activity
increased zinc protoporphyrin and basophilic stippling
testing strategies to find lead toxicity
mercury
inhalation and accidental ingestion of inorganic and organic forms in industrial settings; consumption of contaminated foods is major source of exposure; causes toxicity due to protein binding leading to GI issues, renal impact, behavioral changes, loss of balance, hypotension, bradycardia, and others; analysis by AAS using whole blood
pesticides
substances intentionally added to environment to kill or harm insects or plants impacting something else; contamination of food is major route of exposure; inhalation, transdermal and ingestion are exposure routes; lead to wide range of toxicity, both chronic and acute, and death
measurement of pseudocholinesterase (SChE) activity
more common measurement for pesticide toxicity
erythrocytic acetylcholinesterase activity
used for the detection of organophosphate exposure to pesticides-less common
salicylates-aspirin
used as an analgesic, antipyretic, and anti-inflammatory drug; decreases thromboxane and prostaglandin formation through inhibition of cyclooxygenase interfering with platelet aggregation and GI function in high amounts; toxic effects include metabolic acidosis (can lead to death), hyperventilation, respiratory alkalosis, acid-base disturbance, inhibition of Krebs cycle, resulting in excess conversion of pyruvate to lactate, and excess ketone body formation; measured by GC, LC, immunoassays, some chromogenic assays
acetaminophen
analgesic drug; overdose associated with severe hepatotoxicity, accumulation of reactive intermediates and free radical leading to toxic cell effect and necrosis of liver-onset usually 3-5 days after ingestion; initial symptoms are vague, nonspecific, and not predictive of hepatic necrosis; tested by immunoassay and high-performance liquid chromatography
amphetamines
therapeutic drugs used for narcolepsy and attention deficit disorder; stimulants with a high abuse potential; produce initial sense of increased mental and physical capacity and perception of well-being; initial effects followed by restlessness, irritability, and possible psychosis; OD: hypertension, cardiac arrhythmias, convulsions, and death; testing through urine, immunoassay screening, confirmed by LC or GC
methylenedioxymethamphetamine (MDMA)
an illicit amphetamine derivative commonly referred to as ecstasy
anabolic steroids
group of compounds related chemically to male sex hormone testosterone; increase muscle mass and can improve athletic performance; toxic hepatitis, accelerated atherosclerosis, abnormal platelet aggregation leading to stroke or MI; enlargement of heart leads to ischemia, cardiac arrhythmias, and possible sudden death; testicular atrophy, sterility, and impotence in males, masculine traits, breast reduction, and sterility in females
cannabinoids
group of psychoactive compounds found in marijuana; smoked or ingested, produces sense of well-being and euphoria; associated with impairment of short-term memory and intellectual function; OD not specific to physiologic toxic outcomes; immunoassay to screen, GC/MS to confirm
tetrahydrocannabinol (THC)
most potent and abundant cannabinoid
cocaine
effective as local anesthetic with few adverse effects at therapeutic concentrations; high concentrations is potent CNS stimulator that elicits sense of excitement and euphoria; high abuse potential; injected or inhaled (crack); half life is brief-30-60 minutes; toxic effects are hypertension, arrhythmia, seizure, and MI; detected by immunoassay to screen GC with MS to confirm
benzoylecgonine
analyte measured to detect cocaine in urine
half life
time it takes for a drug to decrease by 50%
opiates
a class of substances capable of analgesia, sedation, and anesthesia; high abuse potential; derived from opium poppy; leads to respiratory acidosis, myoglobinuria, cardiac damage, and death by cardiopulmonary failure
heroin
chemically modified opiate
phencyclidine
illicit drug (never therapeutic) with stimulant, depressant, anesthetic, hallucinogenic properties; high abuse potential; leads to agitation, hostility, and paranoia; toxic effects are stupor and coma; IA screening, mass GC spec confirmatory
sedative-hypnotics
CNS depressants including tranquilizers; wide range of therapeutic roles; barbs and benzos commonly abused; toxic effects include lethargy, slurred speech, coma, respiratory depression, and hypotension; includes lithium, adovan, valium; GC mass spec or LC