How flunitrazepam works
Flunitrazepam – like other members of the benzodiazepine class – acts as a so-called allosteric modulator at the GABA receptor. Allosteric modulators facilitate the binding of the natural messenger GABA to its binding site (receptor) without activating it themselves.
Signal transmission between nerve cells in the brain occurs via narrow, gap-like contact sites (known as synapses). One cell releases a messenger substance (neurotransmitter) into the synaptic cleft, which binds to suitable receptors of the following cell and is thus perceived by it.
Depending on the type of neurotransmitter and the receptor, the mediated signal can be either excitatory or inhibitory. For example, the neurotransmitter GABA (gamma-aminobutyric acid) transmits an inhibitory signal at the GABA receptor. If this signaling pathway is stimulated by drugs such as flunitrazepam, the patient first becomes calmer, then tired, and finally falls asleep.
Older patients in particular, however, may react paradoxically to treatment with flunitrazepam: Instead of a calming and sleep-promoting effect, aggressive behavior, delusions and excitability may develop.
This is particularly important for long-term use. Tolerances can occur with flunitrazepam and other active substances in the group after just a few weeks. This means that despite the same dosage, the efficacy of the drugs decreases. For a consistent effect, therefore, higher and higher doses must be taken – a physical dependence results.
At the same time, due to the effect of flunitrazepam, which is perceived as pleasant and calming, a psychological dependence can also develop. In this case, the dose is usually not increased further. However, it is extremely difficult to stop taking the drug again because those affected do not want to give it up.
For these reasons, benzodiazepines such as flunitrazepam should not be taken for longer than two to four weeks at a time.
Absorption, breakdown and excretion
After ingestion as a tablet on an empty stomach, the active substance is rapidly and almost completely absorbed into the blood via the intestinal wall. After about twenty minutes, half of the ingested active ingredient has already reached the bloodstream and passes through the blood-brain barrier into the brain.
When is flunitrazepam used?
Flunitrazepam is approved for the short-term treatment of sleep disorders, but now plays almost no role in this area of application.
Treatment must be as short as possible, otherwise habituation and dependence can occur quickly. After only one week of use, spontaneous discontinuation of the sleeping pill often leads to withdrawal symptoms.
How flunitrazepam is used
For the treatment of sleep disorders, flunitrazepam is taken as a tablet immediately before bedtime. The usual dosage is one-half to one milligram of flunitrazepam at night.
After taking the drug, elderly patients in particular should not get out of bed, as there is an increased risk of falling. If the active substance has been used for more than a week, it should be gradually discontinued (“phased out”) to end treatment.
Due to the long half-life of flunitrazepam, a so-called “hang-over effect” often occurs (persistent tiredness the following day).
What are the side effects of flunitrazepam?
In addition, breathing may slow down to the point of respiratory arrest. This risk is particularly present in the presence of pulmonary dysfunction (such as asthma and COPD), brain damage, or concomitant use of other drugs with the same side effect.
Flunitrazepam is known to cause “anterograde amnesia” (forward memory loss) comparatively often: After taking the drug, some people are unable to remember things that happened in the interim on the following day.
Because of the possible side effects of amnesia, flunitrazepam is sometimes misused as a “date rape drug” (knockout drops). This has contributed significantly to its bad reputation.
What should be considered when taking flunitrazepam?
Contraindications
Flunitrazepam should not be taken by:
- hypersensitivity to the active substance, other benzodiazepines, or any of the other ingredients of the drug
- acute intoxication
- history of dependence
- myasthenia gravis (abnormal muscle weakness)
- severe respiratory failure (respiratory insufficiency)
- obstructive sleep apnea (most common form of sleep apnea)
- severe liver dysfunction
Mode of action
For example, flunitrazepam increases the effect of antifungal drugs (such as ketoconazole, fluconazole), some HIV drugs (such as ritonavir, nelfinavir), macrolide antibiotics (such as erythromycin, clarithromycin), cholesterol-lowering drugs (such as atorvastatin, simvastatin), and antihypertensive drugs (such as verapamil). Grapefruit juice may also increase the effect of the sleeping pill.
Conversely, epilepsy medications such as phenobarbital, phenytoin, and carbamazepine, as well as the herbal antidepressant St. John’s wort, may accelerate the breakdown of flunitrazepam and thus decrease its effect.
Concomitant use of agents that have a sedative or sleep-inducing effect as a side effect may increase the effect of flunitrazepam in an unpredictable manner. These include other sleep and sedative medications, anti-anxiety medications, anti-allergy agents, antidepressants, neuroleptics (agents for psychotic symptoms such as hallucinations), and agents for seizure disorders.
Driving and operating heavy machinery
Patients should not operate heavy machinery or drive motor vehicles during treatment with flunitrazepam.
Age Limitation
Flunitrazepam should not be used in children and adolescents under 18 years of age.
Pregnancy and lactation
Flunitrazepam passes into breast milk and may accumulate there. Single doses do not usually require a break from breastfeeding. If a breastfeeding mother is absolutely dependent on particularly high doses or multiple doses, the expert information recommends weaning off to be on the safe side.
How to obtain medication with flunitrazepam
Unlike other benzodiazepines, flunitrazepam is not listed as an “exempt preparation” in the German and Swiss narcotics laws or the Austrian Narcotics Act.
This means that all other benzodiazepines below a certain dosage and package size may be sold in pharmacies as normal prescription drugs. The prescription of flunitrazepam, on the other hand, requires a narcotic prescription (Germany, Switzerland) or an addictive drug prescription (Austria) for every dosage and package size.
How long has flunitrazepam been known?
Flunitrazepam was patented in 1972. It was first marketed in several European countries in 1975. Because of the potential for abuse, a single dose (tablet) may not contain more than one milligram of active ingredient since 1998 (previously there were also tablets with two milligrams of flunitrazepam each).
