Posted by hawkeye on October 20, 2005, at 15:40:22
In reply to dexadrine, posted by jetskiier on October 20, 2005, at 14:07:53
"Medical Review Officer Manual
for Federal Agency Workplace Drug Testing ProgramsFor use with the new Federal Drug Testing Custody and Control Form
(OMB Number 0930-0158, Exp Date: June 30, 2003)
This manual applies to Federal agency drug testing programs that come under Executive Order 12564 and the Department of Health and Human Services (HHS) Mandatory Guidelines.............
Chapter 4. Specific Drug Class Issues
A. Amphetamines
1. Background
Amphetamine and methamphetamine are substances regulated under the Controlled Substances Act (CSA, 21 U.S.C. § 801 et seq.), and implementing regulations as Schedule II stimulants (see 21 CFR § 1308.12(d)). Schedule II substances have legitimate medical uses, but also have a high potential for abuse. Both drugs have been used for treating attention deficit disorder in children, obesity, and narcolepsy.
Amphetamine and methamphetamine are central nervous system stimulants. A single therapeutic dose often enhances attention and performance, but exhaustion eventually occurs and performance deteriorates as the effects wear off. Frequently, repeated high-dose use produces lethargy, exhaustion, mental confusion, and paranoid thoughts.
Tolerance can develop to the effects of amphetamine and methamphetamine. A typical therapeutic dose is five milligrams. Individuals who abuse these drugs are reported to inject up to one gram in a single intravenous dose. Physical dependence is modest. Lethargy, drowsiness, hyperphagia, vivid dreams, and some mental depression may persist for a few days to several weeks after abrupt termination of repeated high doses.
Amphetamine and methamphetamine are usually taken orally as tablets or capsules. Abusers inject the drugs intravenously, sometimes take them by intranasal "snorting," and by smoking. Absorption from the gastrointestinal tract is good and they are distributed throughout the body.
2. Metabolism and Excretion
Nearly half of a methamphetamine dose is recovered from urine unchanged. A small percentage is demethylated to amphetamine and its metabolites. The excretion rate of methamphetamine is also increased when urine is acidic.
Amphetamine is excreted as both unchanged amphetamine and as hydroxylated metabolites. Typically, about one-quarter of an administered dose is excreted as unchanged amphetamine, but this varies widely with urinary pH; the drug stays in the body longer when urine is alkaline, allowing reabsorption and thus allowing more of it to be metabolized. In 24 hours, about 80 percent of a dose will be excreted if urine is acidic, while less than half is excreted if urine is alkaline.
A single therapeutic dose of amphetamine or methamphetamine can produce a positive urine for about 24 hours depending upon urine pH and individual metabolic differences. High dose abusers may continue to generate positive urine specimens for 2 to 4 days after last use.Methamphetamine and amphetamine exist in two isomeric structural forms known as enantiomers. Enantiomers are non-superimposable mirror images. The two isomers of each substance are designated as d- (dextro) and l- (levo), indicating the direction in which they rotate a beam of polarized light. As do many pharmacological enantiomers, the d- and l- isomers have distinct pharmacological properties. In this case, the d- isomer of each substance has a strong central nervous system stimulant effect while the l- isomer of each substance has primarily a peripheral action.
Generally, the methamphetamine/amphetamine result reported by the laboratory does not indicate which enantiomer is present because the laboratory procedure is set up to only identify and quantify the methamphetamine/amphetamine that is present. In order to determine which enantiomer is present, an additional analysis must be performed.
The enantiomer identification may be useful in determining if a donor has been using a Vicks Inhaler®, a prescription medication, or abusing an illegal drug. The presence of the l- isomer of either amphetamine or methamphetamine does not by itself rule out illegal use.
Illegally manufactured amphetamine and methamphetamine often contain significant amounts of the l- isomer of each substance. This depends on the starting materials used by the clandestine laboratories.
The following prescription medications contain d-amphetamine or racemic d,l-amphetamine (i.e., equal amounts of d- and l-amphetamine):
Adderall®
Benzedrine®
Biphetamine®
Dexedrine®
Durophet®
Obetrol®The following prescription medication contains d-methamphetamine:
Desoxyn® (Gradumet®)The following substances are known to metabolize to methamphetamine (and amphetamine):
Benzphetamine (Didrex®)
Dimethylamphetamine
Famprofazone
Fencamine
Furfenorex
Selegiline (Deprenyl, Eldepryl®)The following substances are known to metabolize to amphetamine:
Amphetaminil
Clobenzorex (Dinintel®, Finedal®)
Ethylamphetamine
Fenethylline (Captagon®)
Fenproporex (Tegisec®)
Mefenorex (Pondinil®)
Mesocarb
PrenylamineNote: These lists are not all inclusive.
3. Interpreting Laboratory ResultThe donor provides the following response:
(a) Claims to have been taking a prescription medication.
(1) The MRO requests the donor to provide a copy of the prescription or the sample bottle with the appropriately labeled prescription.
Note: The prescription must be for a drug that contains either amphetamine, methamphetamine, or a substance that can metabolize to amphetamine or methamphetamine. If the prescription does not satisfy this requirement, the drug in the prescription provided by the donor is not a valid medical explanation for the positive amphetamine result and the "Positive" laboratory result is verified as a "POSITIVE."
Note: If the donor had completed taking the prescribed medication by the time he or she is contacted, the donor may no longer have the prescription bottle. When this occurs, the donor must provide a copy of the medical record that documents the valid medical use of the drug during the time of the drug test. There may be a need to contact the prescribing physician or the pharmacist who filled the prescription to verify the information provided by the donor.
Note: If a donor has been taking a prescription medication that contains methamphetamine or amphetamine for a long time, there must be appropriate justification for their long term use because of the high potential for abuse. The MRO must contact the prescribing physician to express concern that the continued use of the medication may present a significant safety problem for the donor while on the medication.
Note: Selegiline is a brain monoamine oxidase inhibitor used in the adjunctive treatment of Parkinson’s disease and for depression. Selegiline is metabolized to l-methamphetamine and l-amphetamine. A d- and l- isomer differentiation will reveal the presence of only l-methamphetamine and l-amphetamine after the ingestion of Selegiline.
(2) If this alternative medical explanation is substantiated for a specimen containing only l-methamphetamine/l-amphetamine, the MRO must verify and report the result as a "Negative."
(b) Claims to have used a Vicks Inhaler®.
(1) Since the Vicks Inhaler® contains l-methamphetamine, there is a possibility that a laboratory positive result could be reported for l-methamphetamine and/or l-amphetamine.
(2) The MRO may request the laboratory to perform a d-, l- isomer differentiation.
Note: Although one would expect to see 100% l-methamphetamine following Vicks Inhaler® use, there may be a trace amount of d- isomer present because a very slight amount of d-methamphetamine may be present as a contaminant in the Vicks Inhaler® and a contaminant of the analytical procedure.
(3) After the laboratory conducts the isomer differentiation, if there is greater than 80% l-methamphetamine, the results are considered to be consistent with Vicks Inhaler® use and the result is verified as a "Negative."
Note: This is a very conservative interpretation.
(4) If there is more than 20% d-methamphetamine present, the results indicate the use of some source other than the inhaler and the result is verified as a "Positive."
(c) Claims to have used other over-the-counter medications.
(1) The MRO would verify the laboratory result as a "Positive."
Note: There are no over-the-counter medications, other than the Vicks Inhaler®, that contain either d- or l- methamphetamine or amphetamine. Although we know that some sympathomimetic amines can test positive on an immunoassay test, they will not be reported positive by the laboratory after conducting the confirmatory test; the confirmatory GC/MS test is specific for methamphetamine and amphetamine.
The NLCP requires that a specimen reported as a "Positive" for methamphetamine only (i.e., above the confirmatory test level of 500 ng/mL), it must also contain amphetamine (which is a metabolite of methamphetamine) at a concentration equal to or greater than 200 ng/mL. The amphetamine will not be reported as "Positive" by the laboratory unless its concentration exceeds the 500 ng/mL confirmatory test level. In the case of a report stating only a methamphetamine positive, the MRO may contact the laboratory to verbally confirm that amphetamine was present between 200 and 500 ng/mL.(d) Admits or denies using any substance illegally. The MRO verifies the result as a "Positive" for amphetamine and/or methamphetamine."
poster:hawkeye
thread:569325
URL: http://www.dr-bob.org/babble/20051017/msgs/569370.html