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Barbiturates
Barbiturates were first introduced for medical use in the early
1900s. More than 2,500 barbiturates have been synthesized, and
at the height of their popularity, about 50 were marketed for
human use. Today, about a dozen are in medical use. Barbiturates
produce a wide spectrum of central nervous system depression,
from mild sedation to coma, and have been used as sedatives,
hypnotics, anesthetics, and anticonvulsants. The primary
differences among many of these products are how fast they
produce an effect and how long those effects last. Barbiturates
are classified as ultrashort, short, intermediate, and
long-acting.
The ultrashort-acting
barbiturates produce anesthesia within about one minute after
intravenous administration. Those in current medical use are the
Schedule IV drug methohexital (Brevital®), and the Schedule III
drugs thiamyl (Surital®) and thiopental (Pentothal®).
Barbiturate abusers prefer the Schedule II short-acting and
intermediate-acting barbiturates that include amobarbital
(Amyta®), pentobarbital (Nembutal®), secobarbital (Seconal®),
and Tuinal (an amobarbital/secobarbital combination product).
Other short and intermediate-acting barbiturates are in Schedule
III and include butalbital (Fiorina®), butabarbital (Butisol®),
talbutal (Lotusate®), and aprobarbital (Alurate®). After oral
administration, the onset of action is from 15 to 40 minutes,
and the effects last up to six hours. These drugs are primarily
used for insomnia and preoperative sedation. Veterinarians use
pentobarbital for anesthesia and euthanasia.
Long-acting barbiturates
include phenobarbital (Luminal®) and mephobarbital (Mebaral®),
both of which are in Schedule IV. Effects of these drugs are
realized in about one hour and last for about 12 hours, and are
used primarily for daytime sedation and the treatment of seizure
disorders.
Detection of Barbiturates
in Urine
Barbiturates have been known
since 1864 when Dr. A. von Bayer synthesized barbituric acid. In
1903, barbital was introduced as a hypnotic for routine
medicinal use. They were reclassified as Schedule 2 drugs in
1979 requiring a triplicate prescription to reduce the abuse of
barbiturates. The benzodiazepines (Valium, Librium, Xanax) are
generally safer in overdose and have largely replaced the use of
barbiturates in medicinal pharmacology. Barbiturates are
numerous, chemically derived from a common 2,4,6
trioxohexahydropyrimidine (barbituric acid) nucleus. Some of the
common names are: phenobarbital (Luminol®), secobarbital
(Seconal®), pentobarbital (Nembutal®), butalbital (Fiorinal®),
amobarbital (Amytal®), and many others.
Pharmacological Effects
Barbiturates reversibly
depress the activity of all excitable tissues. The use of
phenobarbital in epilepsy, one of the few major remaining useful
areas of barbiturate pharmacology, is due to its selective
anticonvulsant activity depressing low frequency electrical
activity in the cortex. Tolerance to barbiturates occurs with
continued use. At first, a generalized sedative effect gives way
to tolerance, especially toward effects on mood, sedation, and
hypnosis. Like other central nervous system depressant drugs,
barbiturates are abused and some individuals develop a
dependence on them. Dependence upon and tolerance to
barbiturates are closely related. The former, generating the
drug seeking behavior that leads to increased usage and
consequent higher levels of tolerance and hence the extent,
duration, and continuity of abuse prior to withdrawal.
Laboratory Methods
POISONLAB utilizes
immunoassay (EIA) for detecting barbiturates in urine. The
immunoassays provide a cost effective, sensitive method for
detection and reacts with a number of barbiturates. Gas
chromatography/mass spectrometry (GC/MS) is used to further
identify and confirm the presence of a particular barbiturate in
the sample.
Cutoff and Detection Post
Dose
The 200 ng/ml cutoff for the screening immunoassay
allows detection of barbiturate use for up to 72 hours post
dose. The cutoff level for GC/MS is 200 ng/ml for all
barbiturate metabolites (amobarbital, butabarbital, butalbital,
pentobarbital, phenobarbital, secobarbital). Various
barbiturates have differing half lives of clearance post dose.
For instance, the short acting barbiturate, secobarbital, has a
half life of 29-34 hours, whil phenobarbital, a long acting
barbiturate, has a half life of 24-140 hours. Thus, use of
phenobarbital may be detected much longer than secobarbital.
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