Flunitrazepam

General supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. Flumazenil (Anexate) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose. In particular, flumazenil is very effective at reversing the CNS depression associated with benzodiazepines but is less effective at reversing respiratory depression. Its use, however, is controversial as it has numerous contraindications. It is contraindicated in patients who are on long-term benzodiazepines, those who have ingested a substance that lowers the seizure threshold, or in patients who have tachycardia or a history of seizures. As a general rule, medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects often outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended.

... The study was conducted/ to determine if the reported clinical adverse interaction of flunitrazepam and buprenorphine was caused by inhibition of drug metabolism. ...: Inhibition of flunitrazepam metabolism by buprenorphine and norbuprenorphine were determined in three human liver microsome preparations carrying the CYP2C19*1/*1 allele. Omeprazole metabolism mediated by CYP2C19 and CYP3A4 was used as a control reaction. Apparent K(i) values were determined. ... Norbuprenorphine did not inhibit the metabolism of flunitrazepam or omeprazole. Buprenorphine inhibited the formation of CYP3A4-mediated pathways of 3-hydroxyflunitrazepam and omeprazole sulfone formation (K(i) 118 and 16 microM) in human liver microsomes. Corresponding values were 38 and 90 microM in cDNA-expressed CYP3A4 microsomes. Projected in vivo inhibition of CYP3A4-mediated metabolism of flunitrazepam by buprenorphine is 0. 1%-2.5%. Estimated inhibition of buprenorphine N-dealkylation by flunitrazepam in vivo is 0.08%. ... The clinical interaction of flunitrazepam and buprenorphine is likely based on a pharmacodynamic mechanism.

High doses of Rohypnol particularly when combined with CNS depressant drugs (e.g., alcohol and heroin) can cause severe sedation, unconsciousness, slow heart rate, and suppression of respiration which may be sufficient to result in death.

Single iv doses of aminophylline 1-2 mg/kg may reverse the sedation induced by ... flunitrazepam ... .

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 170(SRC), determined from a log Kow of 2.06(2) and a regression-derived equation(3), indicates that flunitrazepam is expected to have moderate mobility in soil(SRC). Volatilization of flunitrazepam from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.3X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(6). Flunitrazepam is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.0X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation data in soil were not available(SRC, 2013).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 170(SRC), determined from a log Kow of 2.06(2) and a regression-derived equation(3), indicates that flunitrazepam is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 2.3X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(5), an estimated BCF of 11(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2013).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), flunitrazepam, which has an estimated vapor pressure of 6.0X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase flunitrazepam may be removed from the air by wet and dry deposition(SRC). Flunitrazepam contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

The Koc of flunitrazepam is estimated as 170(SRC), using a log Kow of 2.06(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that flunitrazepam is expected to have moderate mobility in soil.

/HUMAN EXPOSURE STUDIES/ Low, medium, and high doses of flunitrazepam were tested in three independent randomized, double-blind, balanced cross-over, placebo-controlled trials to study the influence of rate of onset of effects and dose administered on its acute effects. Three groups of 12 healthy male volunteers received six oral doses of placebo or flunitrazepam in slow and fast onset conditions as follows: six capsules of 0.16 mg (slow) and a single capsule of 0.8 mg (fast) in the low dose trial; six 0.25 mg (slow) and a single 1.25 mg (fast) capsules for medium dose; and six 0.4 mg (slow) and a single 2 mg (fast) capsule for high dose. At each dose level, slow or fast increasing flunitrazepam plasma concentrations lead to similar peak levels, but induced differential subjective and behavioral effects. In addition to objective and subjective sedation, flunitrazepam induced some pleasurable feelings, which were more intense in the fast than in the slow conditions. At the highest dose, unpleasant sedative effects surmounted positive effects, while at the lowest dose pleasurable effects were of low intensity. At the medium dose, the balance between pleasurable and unpleasant feelings resulted in euphorigenic effects, which were evident in the fast condition but were blunted in the slow condition.

/HUMAN EXPOSURE STUDIES/ This study was designed to explore whether differences in the psychomotor, subjective and memory effects of different benzodiazepines (BDZ) relate to differences in their potencies. Two BDZs with similar kinetics but different potencies were compared. Flunitrazepam (0.5 and 1.0mg, nitrazepam (5 and 10mg) or placebo were administered to 50 healthy volunteers in a double-blind, parallel group design. Subjects completed a test battery before and 1.5 hr post-treatment. The higher dose of the more potent BDZ, flunitrazepam, impaired episodic memory in relation to placebo. In contrast, differences in psychomotor and subjective effects between BDZ were less clear. We conclude that a main caveat to the conclusion that potency plays a role in determining BDZ amnestic effects is the possible contribution of sedation and differential task sensitivities to apparent differential effects of BDZ compounds.

/SIGNS AND SYMPTOMS/ High doses of Rohypnol particularly when combined with CNS depressant drugs (e.g., alcohol and heroin) can cause severe sedation, unconsciousness, slow heart rate, and suppression of respiration which may be sufficient to result in death.

/SIGNS AND SYMPTOMS/ Rohypnol causes muscle relaxation. Adverse physical effects include slurred speech, loss of motor coordination, weakness, headache, and respiratory depression. Rohypnol also can produce physical dependence when taken regularly over a period of time.

For more Human Toxicity Excerpts (Complete) data for FLUNITRAZEPAM (10 total), please visit the HSDB record page.

Schedule IV shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. Depressants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: Flunitrazepam (DEA Code Number: 2763) is included on this list.

MEDICATION

Flunitrazepam is a Schedule IV controlled substance.

Schedule IV Controlled Substance: (A) The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III. (B) The drug or other substance has a currently accepted medical use in treatment in the United States. (C) Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III.

Anti-Anxiety Agents; GABA Modulators

Use (kg; approx.) in Germany (2009): >10

For short-term treatment of severe insomnias, that are not responsive to other hypnotics. Not approved by the FDA in the U.S. In the U.K. it is used (and available only by private prescription) in some hospitals to sedate patients undergoing colonoscopy. In Norway, flunitrazepam is available as a prescription drug to treat insomnia under the brand name Flunipam 1 mg. [Wikipedia]

Street names: Circles, Forget Pill, Forget-Me-Pill, La Rocha, Lunch Money Drug, Mexican Valium, Pingus, R2, Reynolds, Roach, Roach 2, Roaches, Roachies, Roapies, Robutal, Rochas Dos, Rohypnol, Roofies, Rophies, Ropies, Roples, Row-Shay, Ruffies, Wolfies

Trade Names: Flunipam (A. L., Norway), Hypnodorm (Teva, Israel; Alphapharm, Australia), Hipnosedon, Narcozep, Rohpinol, Rohypnol, Roipnol (Hoffmann-La Roche, Switzerland).

Pharmaceuticals -> Nervous System -> Sedatives

Pharmaceuticals