TDM Flashcards
the activity of measuring drug concentrations in blood to determine the dose of the medication to an individual.
Therapeutic drug monitoring (TDM)
central assumption of TDM
relationship between drug concentrations and
efficacy or toxicity outcomes
the study of chemical agents and their effects on
humans.
Pharmacology
only involved therapeutic drugs that are
valuable in the prevention, diagnosis and treatment of diseases.
Pharmacology
part of pharmacology that is concerned primarily
with the application or administration of drugs to patients for the purpose of
prevention and treatment of diseases.
Pharmacotherapeutics
comprises the processes of interaction of pharmacologically
active substances with their target sites and the study of their mechanism of action
in leading to therapeutic or adverse effects.
Pharmacodynamics
processes of uptake, distribution,
biotransformation and elimination of drugs by the body.
Pharmacokinetics
biochemical or physical process that occurs at the site of action and is usually mediated through a receptor.
mechanism of action
reflects the fraction of the dose
administered that reaches the systemic circulation.
bioavailability
Bioavailability of more than ___ is the most practical for drugs to be orally useful except for those with _____
70%
high hepatic rate
acidic drugs are bound
primarily to
albumin
basic drugs
globulins
Most drug metabolism takes
places in the
microsomal fraction of the
hepatocytes
Serum concentrations of the drug rise when the rate of
absorption exceeds distribution
and elimination.
determines the effectiveness of drug
drug concentration
administered initially to achieve the desired blood
concentration quickly
loading dose
consequent drug doses are lower to maintain the desired therapeutic level
maintenance dose).
reached when the amount of drug entering the
body is equal to the amount of drug being eliminated
steady state
The rate at which a drug is cleared from the body is measured by its
half-life
Most drugs are not administered singularly but are delivered on a scheduled basis and with this type of administration, serum drug concentrations would be fluctuating between the
peak level (maximum level)
trough level (minimum drug level).
scheduled administration ensures a trough level within the
therapeutic range
About _____ doses are required before a steady state of fluctuation is acquired.
7
Considerations in analysis of xenobiotics in TDM
time and date of suspected exposure and sample collection
history from patient or witnesses
physical state of patient
most widely used and definitive confirmatory procedure
gas chromatography-mass
spectrometry
analytical factors that affect measurement of drugs
Dose of the drug given to the patient
Specimen collection and handling
Timing of sample collection
Availability of reference methods and their performance characteristics
affect drug concentrations variably through adsorption of the drug by the gel after prolonged contact.
thixotropic gel
preferred anticoagulant for most drug analysis.
Heparin
trough concentrations for most drugs are collected
right before the
next dose
Peak concentrations are drawn ______oral administration.
1 hr
Premature sampling might give
falsely elevated
ability of a given method to
detect a compound of interest among many potential substances present in a
sample.
Method selectivity
a drug-enzyme complex is used as the marker.
enzyme-mediated immunologic technique
These procedures have been applied mainly to the qualitative detection of drugs of
abuse and toxins
thin-layer chromatography (TLC)
high-performance liquid chromatography (HPLC), and gas chromatography-mass spectroscopy (GC-MS)
involves compounds that are directly heated
into the gas phase to make them labile
Gas-liquid chromatography
molecule-ions pass through __ wherein they are separated based on their molecular weight
quadrupole detector
The presence of the molecule-ion on the plate is detected by a
charge multiplier detector system
Non-volatile compounds are detected with
LC-MS
Two interface methods have been
the gold standard for LC-MS:
electrospray (ES
atmospheric pressure chemical ionization (APCI).
URINE advantages
- available in sufficient quantities
- higher concentrations than in blood
- availability of POCT
- well-researched testing techniques
URINE disadvantages
- short to intermediate window of detection
- easy to adulterate or substitute
- may require observed collection
- “shy bladder” syndrome
BLOOD ADVANTAGES
- detects recent drug use
- established laboratory test method
BLOOD DISADVANTAGES
- expensive
- limited window of detection
- poor venous access
HAIR ADVANTAGES
- longest window of detection
- detect changes in drug use over time
(from 7-10 days)
HAIR disadvantages
- cannot detect use within the previous 7-10 days
- difficult to interpret results
- costly and time consuming to
prepare specimen for testing
breath advantages
- well-established method for alcohol testing
- readily available
- used only for alcohol and other volatiles
- short window of detection
- difficult to obtain adequate sample, especially with patients who are very intoxicated or uncooperative
- uncommon in clinical setting
ORAL FLUID/SALIVA advantages
-non-invasive specimen collection
- easy to collect
- reduced risk of adulteration
- directly observed specimen collection
- parent drug rather than the metabolite can be the target of the assay
- able to detect same-day use
- availability of POCTs
- detect residual drug in the mouth
ORAL FLUID/SALIVA disadvantages
- limited specimen volume
- contamination from residual drug in the mouth cannot be correlated with blood concentrations
- short window of detection
- requires supervision for 10-30 minutes before sampling
- salivation reduced by stimulant use
- need for elution solvent to efficiently remove drugs
adsorbed to the collection device - cannabinoids in oral fluid arise from contamination of oral cavity than excretion in saliva from blood
