Flunitrazepam

Done by:
Nedaa Al-Muallem

Introduction
Flunitrazepam (formerly marketed
under the trade name Rohypnol )

is a powerful hypnotic drug which is a

benzodiazepine derivative. It has
powerful hypnotic, sedative, anxiolytic
, and skeletal muscle relaxant
properties. The drug is sometimes
abused as a date rape drug.

History
Flunitrazepam was first synthesized in the
early 1970s by Roche and was used in
hospitals when deep sedation was needed.
It first entered the commercial market in
Europe in 1975, and in the 1980s it began
to be available in other countries. It first
appeared in the U.S. in the early 1990s.
It originally came in 1 mg, 2 mg, and 5 mg
doses, but due to its potency and potential
for abuse the higher doses were soon
taken off the market and it is now only
available in 1 mg.

Pharmacology
flunitrazepam's pharmacological
effects include sedation, muscle
relaxation, reduction in anxiety,
and prevention of convulsions .
However, flunitrazepam's effects
are approximately 7 to 10 times
more potent than diazepam.

Cont.
The effects of flunitrazepam
appear approximately 15 to 20
minutes after oral
administration, and last for
approximately four to six hours.
Some residual effects can
persist up to 12 hours or more
after administration.

Medical uses
In the United States, the drug has not been approved by the
Food and Drug Administration for medical use, and is
considered to be an illegal drug.
In the United Kingdom, the drug is available only by private
prescription. Though Rohypnol was discontinued in 1986,
Rohypnol use is still present in modern culture; among other
uses, it is used in some hospitals to sedate patients undergoing
colonoscopy.
In Australia, prescription is restricted. It is used primarily for
the treatment of severe insomnia that has not responded to
other treatments.
In South Africa, Rohypnol is classified as a schedule 6 drug in. It
is available by prescription only, and restricted to 1 mg doses.
Travelers from South Africa to the United States are limited to a
30-day supply. The drug must be declared to US Customs upon
arrival. If a valid prescription cannot be produced, the drug may
be subject to Customs search and seizure, and the traveler may
face criminal charges or deportation.
In Norway, Rohypnol has been withdrawn from market because
of its reputation, but the drug is still available under the brandname Flunipam.

Drug-facilitated sexual
assault
Flunitrazepam is known to induce
anterograde amnesia in sufficient
doses; individuals are unable to
remember certain events that they
experienced while under the influence
of the drug. This effect is particularly
dangerous when flunitrazepam is used
to aid in the commission of
sexual assault; victims may not be able
to clearly recall the assault, the
assailant, or the events surrounding
the assault.

 If flunitrazepam exposure is to be detected at

all, urine samples need to be collected within 72
hours and subjected to sensitive analytical tests.
The problem is compounded by the onset of
amnesia after ingestion of the drug, which
causes the victim to be uncertain about the
facts surrounding the rape. This uncertainty
may lead to critical delays or even reluctance to
report the rape and provide appropriate
biological samples for testing.
If a person suspects that he or she is the victim
of a flunitrazepam-facilitated rape, he or she
should get laboratory testing for flunitrazepam
as soon as possible.

 It must be noted that an inability to remember

events, including sexual encounters, is not
conclusive evidence of having consumed a
drugged drink: Drunkenness itself causes
blackouts, sleepiness, and a reduction in
inhibitions. Only a timely screening for
flunitrazepam can demonstrate its use.
It has been shown that alcohol alone is the
substance used in the vast majority of cases of
date-rape. A recent study conducted by doctors in
the U.K. found that none of the subjects reporting
spiked drinks had any traces of flunitrazepam or
other medications popularly believed to be
associated with rape such as GHB. The study
claims that binge drinking was to blame.

Drug-facilitated
robbery

In the United Kingdom, the use of flunitrazepam

and other "date rape" drugs has been connected
to stealing from sedated victims. One expert
quoted in a British tabloid estimated that up to
2,000 individuals are robbed each year after
being spiked with powerful sedatives, making
drug-assisted robbery a more common problem
than drug-assisted rape.
Criminals sometimes use flunitrazepam before
committing robbery as it has a calming and antiemotive effect. This allows the criminal to
perform the robbery without becoming anxious.
Flunitrazepam is also known to induce
anterograde amnesia making police
interrogations more difficult.

Recreational drug
flunitrazepam has become widely known in USA for
its use as a date-rape drug, it is used more frequently
as a recreational drug. It is used by high school and
college students, rave party attendees, and heroin
and cocaine users (who call a dose of flunitrazepam a
"roofie") for recreational purposes, including:
To produce profound intoxication (Kurt Cobain
overdosed on a mixture of flunitrazepam and
champagne several weeks before his death)
To boost the high produced by heroin, or ease the
anxiety and/or sleeplessness of withdrawal
To counteract the side effects of stimulants (e.g.
insomnia, paranoia, jitteriness)
To "soften" the so-called "crash" which follows heavy
usage of stimulants, such as cocaine or
methamphetamine
To improve sex drive and appetite.

Cont.
Flunitrazepam is usually consumed
orally, and is often combined with
alcohol. It is also occasionally
insufflated (i.e. tablets are crushed
into powder and snorted). In some
European countries, there was an
alcohol solution of flunitrazepam
(Darkene), taken by injection, with
very strong effects.

Side effects
Flunitrazepam is considered to be one of the most
addictive of the benzodiazepines, along with
clonazepam, midazolam, alprazolam, and
particularily, temazepam, nitrazepam, and
nimetazepam. Its use causes several notable side
effects, including:
Drowsiness
Loss of motor control

Dizziness
Lack of coordination

Slurred speech
Amnesia
Confusion
Gastrointestinal disturbances, lasting 12 or more
hours.
Respiratory depression in higher doses

Cont.
Long-term use of flunitrazepam can
result in psychological and physical
dependence and the appearance of
withdrawal symptoms when the drug
is discontinued.
Flunitrazepam impairs cognitive and
psychomotor functions, affecting
reaction time and driving skill. The
use of this drug in combination with
alcohol potentiates these side
effects, and can lead to toxicity.

HPLC analysis
A new analytical methodology was developed for
simultaneous high-performance liquid
chromatographic quantitation of nitrazepam,
estazolam, flunitrazepam, and triazolam in
plasma. After addition of the internal standard
nor-prazepam, biological samples and calibration
standards were extracted at basic pH into diethyl
ether-methylene chloride (2:1, v/v). The
reconstituted extract was separated on a
reversed-phase Nova Pak C18 column with acidic
buffer (6mM)-acetonitrile-methanol (64:23:13,
v/v) as mobile phase. The detection was
performed at 242 nm. Within-run and day-to-day
precision values were about 2-8%.
The method is thus sensitive and reproducible for
use in clinical and experimental toxicokinetic
studies.

Gas chromatographic
analysis
A rapid method for the determination of flunitrazepam
and desmethylflunitrazepam in human serum in the
range 10-300 ng/ml is described. Both drugs are
isolated from biological material by means of a single
extraction, part of the organic phase is evaporated to
dryness and the residue is dissolved in a small volume
of benzene. Without further purification, the substance
is determined gas chromatographically with an electroncapture detector configuration of 63Ni-type. The
method permits the quantitative determination of at
least 25-300 ng/ml with an overall recovery of
flunitrazepam of 99.7 +/- 4.9% and of
desmethylflunitrazepam of 98.6 +/- 7.8% from serum.
All calculations were carried out by a data system that
was programmed for this purpose. The limit of detection
for flunitrazepam is of the order of 1 ng/ml in serum.
The method is sufficiently sensitive and specific for
therapy control purposes. The time needed for an
analysis is less than 1 h.

Hair Analysis using GCMSNCI

The method involved decontamination of hair
samples with dichloromethane, incubation in
Sorenson buffer (pH 7.6) in the presence of
diazepam-d5 used as internal standard, direct
liquidliquid extraction with diethylether
chloroform (80:20, v/v), derivatization with
heptafluorobutyric anhydride and analysis by
gas chromatography coupled to mass
spectrometry in the negative chemical ionization
mode of detection. Flunitrazepam and its major
metabolite, 7-amino-flunitrazepam, were both
detected. The concentrations determined in the
proximal hair segment were 89.5 and 24.0
pg/mg for flunitrazepam and 7-aminoflunitrazepam, respectively.

PRECAUTIONS
1. Benzodiazepines should not be used alone to
treat depression or anxiety associated with
depression. Suicide may be precipitated in such
patients.
2. The should not be used for phobic or obsessional
states.
3. They should not be used for the treatment of
chronic psychosis.
4. In cases of loss or bereavement, psychological
adjustment may be inhibited by benzodiazepines.
5. Disinhibiting effects may be manifested in various
ways. Suicide may be precipitated in patients who
are depressed, and aggressive behaviour towards
self and others may be precipitated.
Extreme caution should therefore be used in
prescribing benzodiazepines in patients with
personality disorders.

Cont.
6. The lowest dose which can control the
symptoms should be used. It should not
be continued beyond four weeks.
7. Long-term chronic use is not
recommended.
8. Treatment should always be tapered off
gradually.
9. Patients who have taken benzodiazepines
for a long time may require a longer
period during which doses are reduced.
10. When a benzodiazepine is used as a
hypnotic, treatment should, if possible, be
intermittent.