(g) When prescribing a Schedule II or III controlled
substance for 90 (ninety) consecutive days or greater for the treatment of chronic pain arising from conditions
that are not terminal or patients in a nursing home or hospice, a physician must monitor compliance with the therapeutic regimen. This means that body fluid analysis (drug screens) must be performed at least four times a year on a random basis or done at the same frequency proportionate to the period of treatment. Exceptions to the requirement of a clinical visit once every three (3) months may be made for hardship in certain cases and such hardship must be well documented in the patient record. The exception to this monitoring is when the
morphine equivalent daily dose (MEDD) is 30 mg or less. In that case fluid monitoring shall be performed at least once per year.
Toxicology
An understanding of drugs/medications consumed by a patient/person based on
metabolites and parent drug present in bodily fluids (blood, urine, sweat, saliva), organs (liver post-autopsy), and hair or fingernails.
In pain management and other clinical
settings, the most commonly used
matrix is either Urine or Saliva. Profiles
of half lives of drugs present are similar
in both matrices.
Urine most substances taken will be
present for 1-5 days
Saliva most substances taken will be
present 1-3 days
Blood most substances present for 6-8
hours
Urine
Advantages:
-present for longer “window”
-present in higher concentrations as substances have been metabolized by the body and
prepared for elimination through the kidneys. -Some metabolites are also excreted in Feces. Disadvantages:
-requires separate area for collection -“shy bladder”
Oral
Advantages:
-easier collection
-no “shy bladder”
Phase I – modification
In phase I, a variety of enzymes act to introduce reactive and polar groups into their substrates. One of the most common modifications is
hydroxylation catalyzed by the cytochrome P-450-dependent mixed-function oxidase system. Phase I reactions (also termed non-synthetic reactions) may occur by oxidation, reduction, hydrolysis, cyclization, decyclization, and
addition of oxygen or removal of hydrogen,
carried out by mixed function oxidases, often in the liver.
If the metabolites of phase I reactions
are sufficiently polar, they may be
readily excreted at this point. Also some
medications are PRO-DRUGs
.Pro-Drugs
Medications that become active ONLY
AFTER Phase I metabolism
Hydrocodone to Hydromorphone
Oxycodone to Oxymorphone
Erroneous interpretation of Toxicology
results can lead to misidentifying abuse
or misuse
Phase II – conjugation
In subsequent phase II reactions, these
activated xenobiotic metabolites are conjugated with charged species such as glutathione (GSH), sulfate, glycine, or glucuronic acid. Sites on
drugs where conjugation reactions occur include carboxyl (-COOH), hydroxyl (-OH), amino (NH2), and sulfhydryl (-SH) groups.
This step attaches large molecules to the
metabolite such that transport must be done by an active pump on the cell membrane
Phase III – further modification and excretion
Conjugates and their metabolites can be excreted from cells in phase III of their
metabolism, with the anionic groups acting as affinity tags for a variety of membrane
transporters of the multidrug resistance protein (MRP) family. These proteins are members of the family of ATP-binding cassette transporters and can catalyze the ATP-dependent transport of a huge variety of hydrophobic anions, and thus act to remove phase II products to the extracellular medium, where they may be further metabolized or excreted.
FOCUS TODAY
Urine Drug Screening and Testing
-most commonly employed matrix in clinical setting
-principles directly translate to saliva testing with the following exceptions:
Morphine, Benzodiazepines not as easily detected
THC can be detected immediately following inspiration or mastication reliably up to 15 hours
THC-COOH is identified in the urine from hours after intake to days later
Urine Drug Screening
-based on an immunoassay reaction -can be performed in the office as POCT
-ease of administration -no formal training
-results in minutes
-decreased ability to identify the drug and possibility of mis-identifying the drug
Cups package insert makes claims of up to 99% but not in real world conditions
Formal Immunoassay Testing Advantages:
-Increased accuracy
Importance for confirmation testing because of insurer demands MCR, MCD, Private
Confirmation testing is only reimbursed to
identify the presence/absence of “Presumptive Positives” or “Unexpected Negatives”
Disadvantages: -expense
-specialized testing equipment 100k range and expensive reagents
-off sight service in most cases -requires specific training and PT
Confirmation testing is
only reimbursed to identify
the presence/absence of
“Presumptive Positives” or
“Unexpected Negatives”
Confirmation Testing
GCMS/LCMS/LCMSMS
LCMSMS is the current gold standard of
testing
Advantage:
Absolute results with 99.5% or greater accuracy when done with LCMSMS
Identification of any substance within the Machine library
-up to 100 or more Drugs and Analytes including Illicit drugs
Disadvantage:
Elaborate equipment and support staff including Masters and PhD level analytic chemists
Expense of reagents
