FTK 4: Toxicology Principles Flashcards
definitions
toxicant?
toxin?
toxicity?
dose?
dosage?
threshold dose?
TOXICANT = aka POISON, ANY substance that is capable of producing a DELETERIOUS response in a biological system
TOXIN = aka BIOTOXIN, POISON that originates from BIOLOGICAL PROCESSES
TOXICITY = AMOUNT of toxicant needed to produce TOXIC EFFECTS
DOSE = AMOUNT of TOXICANT given (like a pill)
DOSAGE = AMOUNT of TOXICANT per UNIT OF ANIMAL MASS or WEIGHT
THRESHOLD DOSE = experimentally, the HIGHEST dose of a toxicant at which TOXIC EFFECTS ARE NOT OBSERVED
more definitions
median lethal dose?
no observed (adverse) level of effect?
LOW observed (adverse) level of effect?
therapeutic index? what does it mean if it’s high?
standard safety margin? what does it mean if it’s high?
MEDIAN LETHAL DOSE = LD50
NOAEL = NOTHING HAPPENED
LOALOE? = MIGHT be getting into range where we see clinical signs
THERAPEUTIC INDEX = LD50/ED50
–> the HIGHER it is, the MORE WIGGLE ROOM WE HAVE BETWEEN EFFECTIVE & LETHAL DOSE
STANDARD SAFETY MARGIN = LD1/ED99
–> HIGHER = SAFER
3 most common routes of toxin exposure?
- INHALED
- DERMAL
- ORAL
DURATION of exposure…
Acute, subacute, subchronic, chronic
ACUTE = SINGLE or MULTIPLE doses up to 24 HOURS
SUBACUTE = MULTIPLE doses between GREATER than 24 hours and up to 30 DAYS
SUBCHRONIC = 1-3 MONTHS
CHRONIC = 3 MONTHS OR LONGER
3 ways that CHRONIC TOXIC EFFECTS can occur
- chemical ACCUMULATES
- toxic effects are IRREVERSIBLE
- INSUFFICIENT recovery time BETWEEN EXPOSURES
potentiation definition
= when a normally non- or mildly-toxic substance ENHANCES toxicity of another
ISOPROPANOL IS NOT HEPATOTOXIC, but will ENHANCE the hepatotoxicity of CARBON TETRACHLORIDE
dose-response concept
= definition
3 assumptions?
= there is SOME MEASURABLE EFFECT that is PROPORTIONAL to the AMOUNT OF CHEMICAL ADMINISTERED
3 assumptions…
1. chemical will interact with MOLECULE or RECEPTOR SITE to PRODUCE RESPONSE
- the PRODUCTION of response or DEGREE of response correlates to CONCENTRATION of chemical at receptor site
- CONCENTRATION of chemical at receptor site is proportional to AMOUNT OF CHEMICAL RECEIVED
INHALATION of toxins
what 3 regions does it most likely occur?
before reaching more internal structures, where else can drug be inhaled/absorbed?
how can inhaled drugs reach SYSTEMIC circulation?
selectivity for inhaled drugs reaching certain regions?
3 most common regions?
1. upper respiratory tract
2. lower respiratory tract
3. alveoli
before reaching internal structures, can be ABSORBED IN NASAL PASSAGES
drugs can reach SYSTEMIC circulation if they reach ALVEOLI
inhaled drugs can be SELECTIVE for UPPER or LOWER respiratory tract based on their SOLUBILITY in blood which is determined by BLOOD/GAS PARTITION COEFFICIENT
MOST to LEAST efficient routes of exposure? (8)
- IV
- Inhalation
- IP
- SQ
- IM
- ID
- Oral
- Dermal
DERMAL exposure to toxins
what’s needed for it to occur?
when does it commonly occur?
need chemical in a SOLUBLE form that can PENETRATE KERATINIZED EPIDERMIS and eventually REACH A BLOOD VESSEL
commonly occurs in COMPROMISED SKIN
ORAL exposure to toxins
relation to INHALED substances?
chemicals in the STOMACH?
chemicals in the SI?
LARGE molecules? what can be a decontamination method for large molecules?
INHALED substances?
some INHALED substances can reach GI tract via MUCOCILIARY apparatus
chemicals in stomach?
will be either DEGRADED or ABSORBED in stomach acid environment
chemicals in SI?
can undergo enterohepatic circulation via portal vein that PROLONGS effect
LARGE molecules?
often absorbed in large intestine or eliminated in feces!
ENEMA can be a decontamination method
if a particular substance has RATIO OF UNIONIZED:IONIZED MOLECULES, then…
they are MORE LIKELY TO BE ABSORBED
most substances are absorbed via…
which favors…
PASSIVE TRANSPORT SIMPLE DIFFUSION
which favors UNCHARGED, lipophilic substances
facilitated transport ____ energy but DOES ___ MOVE AGAINST ___ ____
EXPENDS, NOT, CONCENTRATION GRADIENT
passive transport is ____, while active transport is _______
NON-saturable, SATURABLE
distribution
= definition
3 things that determine its RATE?
= the RATE at which drug LEAVES BLOOD & enters ORGANS/TISSUES
3 things that determine its RATE
1. rate of BLOOD FLOW to TISSUE/ORGAN, can change with patient’s health status
- chemical’s ability to PASS THROUGH CAPILLARY ENDOTHELIUM/be filtered by kidneys –> CANNOT DO THIS IF BOUND TO PLASMA PROTEIN
- physiochemical properties like LIPOPHILICITY
blood-brain barrier
3 reasons that TOXICANTS generally DO NOT ENTER?
what toxicants DO enter? what enhances their CNS penetration?
3 reasons?
1. CNS capillary endothelial cells are TIGHTLY JOINED so FEW TO NO PORES
- GLIAL CELL PROCESSES (astrocytes) are SURROUND CNS CAPILLARIES
- Brain capillary endothelial cells release MULTIDRUG-RESISTANT PROTEIN into blood
UNBOUND, FREE TOXICANTS will EQUILIBRATE in brain
INCREASED LIPOPHILICITY will ENHANCE CNS penetration
4 regions where TOXICANTS can be stored?
include where MOST are stored, which one is a particularly good storage site for a certain toxicant, and an example
- plasma protein (globulin, transferrin, albumin)
- liver/kidney –> where MOST toxicants are stored!
- fat –> good for LIPOPHILIC toxicant storage
- bone –> LEAD IS NOT TOXIC TO BONE, but if lead is stored in bone & mom mobilizes Ca during lactation, can cause ACUTE LEAD TOXICITY
metabolism
which organ possesses MOST metabolic activity?
3 characteristics of IDEAL metabolic system?
LIVER possesses MOST metabolic activity
3 characteristics?
1. produce METABOLITES that are WATER-SOLUBLE to be efficiently ELIMINATED in URINE & BILE
- metabolites themselves should be NON-TOXIC
- ENZYMES responsible for PRODUCING metabolites should have BROAD SUBSTRATE SPECIFICITY to be able to properly handle ANY NEW SUBSTANCE
Phase I metabolism
= definition
3 processes?
Phase II metabolism
= definition
2 processes?
PHASE I = conversion of APOLAR, LIPOPHILIC substances into POLAR, HYDROPHILIC METABOLITES via introduction/liberation of functional groups
- hydrolysis
- oxidation
- reduction
PHASE II = CONJUGATES either CHEMICAL ITSELF or METABOLITE formed in phase I to FUNCTIONAL GROUP that causes MULTIFOLD INCREASE in HYDROPHILICITY
- glucuronidation –> IN ALL EXCEPT CATS
- sulfation –> PIGS DON’T DO THIS WELL
basics of why acetaminophen is TOXIC in cats?
cats CANNOT GLUCURONIDATE, so that means CYTOCHROME P450 will CONVERT ACETOMINOPHEN into a compound that binds to HEPATIC PROTEINS and causes CENTRILOBULAR NECROSIS –> LIVER FAILURE
excretion
most COMMON route of excretion? why is this important?
2 fates for chemicals/metabolites formed in liver?
5 other routes of excretion?
how are toxicants on the SKIN removed?
most COMMON route of excretion = RENAL via URINE
–> important because this is why we give IV FLUIDS in hospital
2 fates?
1. chemicals/metabolites excreted DIRECTLY into BILE –> FECES
- chemicals/metabolites absorbed in SI and ENTEROHEPATIC RECIRCULATION (activated charcoal can help)
5 other routes of excretion?
1. CSF
2. Sweat
3. milk
4. exhalation
5. saliva
toxicants on SKIN removed via NORMAL SLOUGHING
most chemicals are eliminated via WHAT order of kinetics? what does it mean?
SATURABLE or NON-SATURABLE pathways?
FIRST-ORDER
rate of ELIMINATION of a chemical is PROPORTIONAL to the AMOUNT of chemical in the BODY AT THAT TIME
NON-SATURABLE pathways
after ___ half-lives, 99.2% of drug is eliminated
SEVEN
1 ppm is equal to… (5)
= 1 mg/kg
= 0.91 g/ton
= 1 microgram/mL
= 1000 ppb
= 1 million ppt
% to…
ppm?
mL?
% to ppm? –> move decimal 4 PLACES TO RIGHT
% to mL –> move decimal 1 PLACE TO RIGHT
1 oz –> g? mL?
1 cup –> oz?
1 pint –> oz? cups? real-world item?
1 teaspoon? mL? real-world item?
1 tablespoon? mL? real-world item?
1 oz = ~30 g and 30 mL
1 cup = 8 oz
1 pint = 16 oz, 2 cups, ZIPLOC BAGGIE
1 teaspoon = 5 mL, 2 mini marshmallows
1 tablespoon = 15 mL, one large marshmallow
