Therapeutic Drug Monitoring Flashcards
MEC
minimum effective concentration
MTC
minimum toxic concentration
Trough
lowest drug level
draw sample prior to next dose given
peak
highest drug level, draws at peak of absorption for particular drugs
steady state
drug intake & outtake equal so drug level stays in therapeutic range
bioavailability
unchanged drug entering the bloodstream
of doses to get to therapeutic range usually
at least 5 doses
Drug distribution
administration
absorption
distribution
excretion
methods that lead to GI absorption
oral, rectal or sublingual routes of administration
GI absorption
drugs go through the liver & go through ‘first pass’
drug must go through unionized (hydrophobic), absorb passive diffusion
portion of unchanged drug entering the blood is bioavailable
injected drugs absorption
enter the blood stream via IV, intramuscular, intradermal, subcutaneous, respiratory, or percutaneous
do not have to deal with liver’s first pass effect
factors that change drug absorption in GI
GI motility
pH
inflamed
carrier proteins of drugs
albumin & alpha-1-acid glycoprotein (!!!)
free drug levels affected by:
protein binding disease state kidney function additional drugs being present hepatic disease acid-base disturbance nephrotic syndrome
lipid soluble drug distribution
travel through cell membranes & partition in lipid compartments in cells
polar drug distribution
travel to water part of cell & stay there
ionized drug distribution
diffuse slowly out of blood & into cells
get filtered in kidneys or taken out by liver
major organ for drug metabolism
liver via mixed function oxidase system or MFO
converts hydrophobic drug into water soluble substances
go out bile or into blood & out the kidney
secondary sites for drug metabolism
lungs kidneys skin brain GI
drug metabolite activity levels
bound drug & active metabolite
metabolism of lipid soluble drugs
non-polar to soluble form using renal excretion via hydroxylation, deamination, sulfoxidation, dealkylation
enzymes: Monooxygenases or mixed function enzymes (MFO) in liver
MFO phase I
produce reactive intermediates from drug
can accumulate & may not be able to go into phase iI
MFO phase II
conjugates reactive intermediate to water-soluble products
intermediates are conjugated to glutathione, glycine, phophate or sulfate
MFO system influenced
process is inducible
drug-drug interactions are competing for MFO system
changes in hepatic health will affect MFO
renal clearance
parent drug & metabolite are subject to glomerular filtration
if renal function is compromised, then longer half-life
acid urine
leads to more alkaline drug excretion & vice versa
samples
usually serum/plasma
urine samples are used when wanting to look at parent drug & metabolites
cardiac drugs
digoxin/ digitoxin
quinidine
procainamide
disopypramide/norpace
digoxin/digitoxin
used for CHF
very toxic - tissue levels are 15-30x the serum/plasma level
stays in lipid portion of tissues
stops Na/K ATPase pumps to prevent fluid build up in cells & encourage K to be excreted in the urine
quinidine
DO NOT MIX W/ DIGOXIN
cardiac drug
procainamide
active metabolite - NAPA
cardiac drug
disopypramide/norpace
used as quinidine substitute drug
cardiac drug
anti-epileptic drugs
all are GI absorbed, liver metabolized & renal excreted
older AEDs
highly bound to protein; all toxic phenobarbital phenytoin/dilantin valproic acid primidone carbamazepine
2nd gen AEDs
felbamate gabapentin lamotrigine tiagabine topiramate
aminoglycosides
anti-microbials: gentamycin, kanamycin, tobramycin, neomycin
give by IV
bind to ribosomes & inhibit protein synthesis
anti-microbial side effects
affect hearing, balance anemia, cytopenias red man syndrome nephrotoxic ototoxic
vancomycin
affects cell walls of bacteria
G +
Tricyclic antidepressants (TCAs)
takes 2-4 weeks to see effects; drug metabolized by liver
imipramine, amitriptyline, dozepin
Tricyclic antidepressants (TCAs)
takes 2-4 weeks to see effects; drug metabolized by liver
imipramine, amitriptyline, dozepin
Clozepine
used for schizophrenia
Olanzapine
used for schizophrenia
lose 40% to first pass through liver
given IV
immunosuppressive drug specimens
all collected in EDTA due to drug affiliation w/ RBCs
immunosuppressive drugs
cyclosporine tacrolimus sirolimus mycophenolic acid all are eliminated through liver
