Toxicokinetics Flashcards
what is toxicokinetics
study of absorption, distribution, biotransformation and excretion of toxic agents
importance of studying toxicokinetics
knowing the routes of exposure
knowing distribution of poison to target organs (site of action) - clinical signs
selection of proper specimens for chemical analysis
knowing sites of storage
elimination and half life - withdrawal/quarantine periods
drugs and toxicants are
xenobiotics (foreign chemicals)
what is the most common route of exposure in toxicology
oral
which cases is dermal route important
insecticides
inhalation is important with
toxic gases and insecticides
what is lethal synthesis
metabolite is more than the parent compound is important in toxicology
ex: organophosphates and ethylene glycol
drug disposition
study of movement of drugs in the body across biological memebranes from time of absorption until elimination
stages of drug disposition
absorption
distribution
biotransformation
excretion
T/F bulkflow of water can carry with it small water-soluble substances
True
factors that effect simple diffusion
concentration gradient
lipid solubilty
degree of ionization (drugs cross biological membranes in nonionized form)
rate of diffusion depends on…
the ratio of non ionized to ionized
ionization of the drug depends on
pH of drug
pKa of drug
pH of medium (environment)
what is the pKa
the pH at which a weak electrolyte is 50% ionized and 50% non ionized
most drugs are weak electrolytes (weak acids/bases)
drug absorption
transfer of the drug from site of administration to the circulation
factors related to the drug that affect absorption
molecular size
lipid solubility (increases with increased solubiltiy)
degree of ionization
dissolution of drug in water (liquid faster than solid)
concentration of drug
route of administration
is anyone else having pharm flashbacks
I mean his notes even say “drug” and not “toxicant”
factors related to the animal that effect absorption
blood flow
absorbing surface area
connective tissue
species
individual
drug metabolism (biotransformation)
chemical alteration of the drug molecule by the cells of the animal
results of biotransformation
change physiochemical properties of the drug (water soluble, polar, ionized etc)
change pharmacological activity (bioinactivation/activation, detoxification, lethal synthesis)
sites of biotransformation
liver
other tissues - nervous tissue, kidney, GI
plasma
T/F liver enzymes lacl specificity
true
T/F enzymatic reactions are saturable and drugs can compete on the same enzyme
True
microsomal enzymes cause
oxidation, reduction, hydrolysis and conjugation to glucuronic acid
types of metabolic reactions
phase 1 (oxidation, reduction, hydrolysis)
phase 2- synthetic (conjugation)
factors altering biotransformation
species
individual
route of administration
enzyme inducers
enzyme inhibitors
liver disease
enzyme inducers
drugs that stimulate the liver to produce more metabolic enzymes
only microsomal enzymes are inducible by drugs
enzyme induction is reversible/irreversible
reversible
enzyme induction may lead to
tolerance or drug-drug interactions
enzyme inhibitors
drugs that inhibit the liver to produce metabolic enzymes
may lead to drug-drug interactions
newborns are geriatric patients may have more/less biotransformation than adults
less
excretion
removal or clearance of the drug from the body
routes of drug excretion
renal
hepatic
feces
milk
semen
saliva
eggs
hair/feathers
sweat glands
expired air
methods of renal excretion
glomerular filtration
active tubular secretion
tubular reabsorption
