Flunitrazepam (Drugs / Substance abuse)

flunitrazepamFlunitrazepam also known as Narcozep, Rohypnol, Rohipnol, Roipnol, or in the vernacular, simply roofies — is an intermediate acting benzodiazepine used as an hypnotic, sedative, anticonvulsant, anxiolytic and skeletal muscle relaxant drug.

In general, the prescription of flunitrazepam as a hypnotic is intended to be for short-term treatment of chronic or severe insomniacs not responsive to other hypnotics, especially in inpatients. It is considered to be one of the most effective benzodiazepine hypnotics on a dose basis. Just as with other hypnotics, flunitrazepam should be strictly used only on a short-term basis or in those with chronic insomnia on an occasional basis.

Flunitrazepam is classed as a nitro-benzodiazepine. It is the fluorinated methylamino derivative of nitrazepam. Other nitro-benzodiazepines include nitrazepam (the parent compound), nimetazepam (methylamino derivative) and clonazepam (the chlorinated derivative).

Flunitrazepam has been referred to as a date rape drug because of its high potency and ability to cause strong amnesia. However, Robertson’s study indicated that flunitrazepam was used in only around 1% of reported date rapes and 0.33% according to urine lab tests done by El Sohly.

Interactions
The use of flunitrazepam in combination with alcohol synergizes the adverse effects, and can lead to toxicity and death.

Flunitrazepam is metabolized almost completely by cytochrome P450-3A4. Atorvastatin administration along with flunitrazepam results in a reduced elimination rate of this molecule. Grapefruit juice reduces intestinal 3A4 and results in less metabolism and higher plasma concentrations of flunitrazepam, which could result in overdose.

Overdose

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Flunitrazepam is a drug that is frequently involved in drug intoxication, including overdose. Overdose of flunitrazepam may result in excessive sedation, or impairment of balance or speech. This may progress in severe overdoses to respiratory depression or coma and possibly death. The risk of overdose is increased if flunitrazepam is taken in combination with CNS depressants such as alcohol and opiates. Flunitrazepam overdose responds to the benzodiazepine receptor antagonist flumazenil, which thus can be used as a treatment.

Presence In Bodily Fluids
Flunitrazepam can be measured in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest, or assist in a medicolegal death investigation. Blood or plasma flunitrazepam concentrations are usually in a range of 5-20 μg/L in persons receiving the drug therapeutically as a nighttime hypnotic, 10-50 μg/L in those arrested for impaired driving and 100-1000 μg/L in victims of acute fatal overdosage. Urine is often the preferred specimen for routine drug abuse monitoring purposes. The presence of 7-aminoflunitrazepam, a pharmacologically-active metabolite and in vitro degradation product, is useful for confirmation of flunitrazepam ingestion. In postmortem specimens, the parent drug may have been entirely degraded over time to 7-aminoflunitrazepam.

Other Uses

Recreational Use
A 1989 journal on Clinical Pharmacology reports that benzodiazepines, including flunitrazepam, accounted for the largest volume of forged drug prescriptions in Sweden, a total of 52% of drug forgeries being for benzodiazepines, suggesting that benzodiazepines was a major prescription drug class of abuse. Nitrazepam and flunitrazepam accounted for the vast majority of forged prescriptions.

Flunitrazepam and other sedative hypnotic drugs are detected frequently in cases of people suspected of driving under the influence of drugs. Other benzodiazepines (anxiolytic or hypnotic) and zolpidem and zopiclone (as well as similar hypnotic and anxiolytic drugs from the non-benzodiazepine families cyclopyrrolones, imidazopyridines, and pyrazolopyrimidines) are also found in high numbers of suspected drugged drivers. Many drivers have blood levels far exceeding the therapeutic dose range suggesting a high degree of abuse potential for benzodiazepines and similar drugs.

Suicide
In studies in Sweden, flunitrazepam was the second-most-common drug used in suicides, being found in about 16% of cases. In a retrospective Swedish study of 1587 deaths, in 159 cases benzodiazepines were found. In suicides when benzodiazepines were implicated, the benzodiazepines flunitrazepam and nitrazepam were occurring in significantly higher concentrations, compared to natural deaths. In four of the 159 cases, where benzodiazepines were found, benzodiazepines alone were the only cause of death. It was concluded that flunitrazepam and nitrazepam might be more toxic than other benzodiazepines.

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 be unable to clearly recall the assault, the assailant, or the events surrounding the assault.

It is difficult to estimate just how many flunitrazepam-facilitated rapes have occurred. Very often, biological samples are taken from the victim at a time when the effects of the drug have already passed and only residual amounts remain in the body fluids. These residual amounts are difficult, and sometimes impossible, to detect using standard screening assays used in most countries. 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. In recent news, it has been discovered that scientists can now detect flunitrazepam and related compounds in urine at least up to 5 days after administration of a single dose of Rohypnol and up to a month in hair.

An inability to remember events, including sexual encounters, is not conclusive evidence of having consumed a drugged drink: Psychotropic CNS depressant drugs such as alcohol can cause 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 psychotropic substance used in the vast majority of cases of drug-facilitated date-rape. A recent study conducted by doctors in the UK found that none of the subjects reporting spiked drinks had any traces of flunitrazepam or other medications popularly believed to be associated with drug-assisted rape, such as GHB. However, flunitrazepam was prohibited for prescription under the NHS in 1992 (The National Health Service (General Medical Services). Rohypnol (1 mg) is available under private prescription. The study results, however, suggest that binge drinking is more commonly a factor in drug-assisted rapes than pharmaceutical drugs.

Adverse Effects
Adverse effects of flunitrazepam include dependence, both physical and psychological; reduced sleep quality resulting in somnolence; and overdose, resulting in excessive sedation, impairment of balance and speech, respiratory depression or coma, and possibly death. Because of the latter, flunitrazepam is commonly used in suicide. When used in pregnancy, it might cause hypotonia.

Dependence
Flunitrazepam as with other benzodiazepine drugs can lead to physical dependence, addiction, and what is known as the benzodiazepine withdrawal syndrome.

Discontinuation may result in the appearance of withdrawal symptoms when the drug is discontinued. Abrupt withdrawal may lead to a severe benzodiazepine withdrawal syndrome characterised by seizures, psychosis, severe insomnia, and severe anxiety. Rebound insomnia, worse than baseline insomnia, typically occur after discontinuation of flunitrazepam even after short-term single nightly dose therapy.

Sleep Depth
Flunitrazepam produces a decrease in delta wave activity. The effect of benzodiazepine drugs on delta waves, however, may not be mediated via benzodiazepine receptors. Delta activity is an indicator of depth of sleep within non-REM sleep; increased levels of delta sleep reflects better quality of sleep. Thus, flunitrazepam and other benzodiazepines cause a deterioration in sleep quality. Cyproheptadine may be superior to benzodiazepines in the treatment of insomnia as it enhances sleep quality based on EEG studies. This may lead to somnolence.

Paradoxical Effects
Flunitrazepam may cause a paradoxical reaction in some individuals causing symptoms including anxiety, aggressiveness, agitation, confusion, disinhibition, loss of impulse control, talkativeness, violent behavior, and even convulsions. Paradoxical adverse effects may even lead to criminal behaviour.

Hypotonia
Benzodiazepines such as flunitrazepam are lipophilic and rapidly penetrate membranes and, therefore, rapidly cross over into the placenta with significant uptake of the drug. Use of benzodiazepines including flunitrazepam in late pregnancy, especially high doses, may result in hypotonia, also known as floppy infant syndrome.