Lecture 3-4 Part 1 Flashcards
true or false
it is possible for chronic toxic effects to occur some time even after the exposure has stopped
true
as in the case of asbestos or cigarettes
give an example of something that as a high acute toxicity, yet is a benefit in small doses
vitamin D
oral LD50 is 10mg/kg
we each require a very small amount (10 micrograms/400IU per day) for good health
toxic effects can range from ____ to ____
mild allergic reactions to death
explain what threshold level is
the maximum dose where there are no effects
basically how much the body can tolerate without experiencing any toxic effects (when the defense system gets saturated)
how to quantify a toxic response
the dose response curve
most tolerant route of exposure
the skin
most popular route of exposure
ingestion
quickest and most direct route of exposure
inhalation
what is TD
dose that results in adverse toxic effect - OTHER THAN DEATH
if it was death it would be LD
0 + 2 = >2
what is this and give example
potentiation
isopropanol + carbon tetrachloride
2 + 2 = 4
what is this and give example
additive
ethanol + sedative-hypnotics
2 + 2 >4
what is this and give example
synergistic
ethanol + antihistamine
2+2 = 0
what is this and give example
antagonism
can be functional, chemical, dispositional, or receptor antagonism
ex of functional antagonism
stimulants + depressants
ex of chemical antagonism
metal + chelators
ex of receptor antagonism
tamoxifen + estrogen - compete for same receptor
ex of dispositional antagonism
activated charcoal + phenobarbital
absorbs the toxins
true or false
ADME is part of toxicodynamics
FALSE - toxicokinetics
toxicokinetics or dynamics:
relationship between the external exposure and the dose delivered to the target organ
toxicokinetics
explain toxicodynamics
bioochemical response at the target site
(could be a lot of things - cell death, DNA dduct formation, etc)
following absorption from any route of administration, what happens to the toxin next
it enters circulation either directly or indirectly
what is BED
biologically effective dose (target organ dose)
what is an idiosyncratic reaction
individual hypersensitivity
toxicokinetics is the study of ___ in ____
drug disposition in the physiological compartment
“biotranslocation: is another word for
distribution
toxicity is determined by ____
accumulation of the compound in physiological compartments
how is a normal dosing schedule determined
by the chemical’s half life
the accumulation of the compound is determined by what 2 things
the physiologic compartment and the chemical structure
define absorption
process by which toxicants cross the body membranes and enter the bloodstrema
4 things that can help absorption across the cell membrane
diffusion barrier
ion channels
pores
transport
2 general transport mechanisms
passive transport
specialized (active) transport
4 factors affecting membrane transport
molecular weight/shape
charge
lipid solubility
membrane composition and thickcness
3 main sites of absorption
GI tract
lungs
skin
acidic compartment traps ___ drugs and basic compartment traps ___ drugs
acidic compartment traps basic drugs and basic compartment traps acidic drugs
the absorption of most drugs is better and more predictable when administered when?
in a fasted state and with a large volume of water
however, drugs that irritate the GI tract should be given with food
what can increase the dissolution of basic drugs in the GI tract
the presence of food – because it causes HCl secretion
what can increase the absorption of lipid soluble drugs in the GI tract
stimulation of bile flow
define first pass effect
removal of orally administered chemicals before they reach systemic circulation
generally, orally administered drugs undergo absorption in the ______ and are transported where
duodenum and transported to the hepatic portal vein by mesenteric vessels before entering systemic circulation
3 ways that 1st pass effects can be avoided
giving diff route
give larger dose
give a form of the drug that absorbs more rapidly
first pass effect is important consideration for drugs that have a high ___–
extraction ratio
(the fraction of oral drug reaching systemic circulation)
true or false
the lungs cannot absorb a large amount of toxic substances
FALSE
they can - have a very large surface area and a lot of blood flow
______ soluble gasses will be readily dissolved in the upper respiratory tract
water soluble
bc the upper respiratory tract contains moisture
name 2 highly water soluble gasses that will readily dissolve in the upper respiratory tract
ammonia and formaldehyde
true or false
some toxic substances can cause harm without being absorbed
true
true or false
pulmonary absorption AVOIDS 1st pass effects
true
there is equilibrium between ___ and ____
blood and tissues
what is a chemical’s “plasma half life”
time taken for the concentration of the compound in the plasma to decrease by half from a given point
what is the most important vehicle for distribution to the body tissues
THE BLOOD
when the substance is distributed throughout the body, it can be ___, ____, or ____
stored, eliminated, or biotransformed (metabolized)
2 determining factors of toxin distribution
blood flow
affinity for a organ/tissue
name 2 things that deposit in bone
tetracyclines and heavy metals
also fluoride and lead
how does the placenta barrier protect the fetus against toxic chemicals from the mother
it has the capability to metabolize
3 routes of excretion
urinary
fecal
exhalation
1st, 2nd, and 3rd most important organs for excretion
kidney, feces, lungs
define extraction
the removal of drug from the blood by an organ
ER (extraction ratio) formula
ER = (Ca-Cv)/Ca
Ca = arterial drug concentration
Cv = venous blood concentration
aka clearance by the organ/blood flow to the organ
when the ER (extraction ratio) approaches 1, what does this mean
the clearance by the organ HIGHLY DEPENDS ON BLOOD FLOW. drug is being removed from the blood almost as rapidly as the organ is being perfused by the blood that contains the drug
FLOW DEPENDENT DRUG METABOLISM
if the ER (extraction ratio) is very low, what does this mean
clearance of the drug by the organ is INDEPENDENT of blood flow
more affected by the activity of metabolizing enzymesd
drugs with a low ER are eliminated primarily by ______
metabolism
3 specific roles of the kidneys
filter the blood
reabsorb any useful material
actively secrete things
things filtered/secreted become part of urine
bases are excreted better at higher or lower urinary pH?
higher
acids are excreted better at higher or lower urinary p
lower
enterohepatic circulation
circulation of substances absorbed from the intestine and carried to the liver
at the liver, they are again excreted into the bile and enter the intestine again
fecal excretion is through the ______
bile
the rate of PULMONARY elimination is inversely proportional to…..
the blood solubility of the compound
the higher the blood solubility, the slower the rate of pulmonary elimination
what is KOW
the octanol-water partition coefficient
