Products
Benzodiazepines are commercially available in the form of tablets, melting tablets, capsules, drops, and injectables, among others (selection). Chlordiazepoxide (Librium), the first benzodiazepine, was synthesized in the 1950s by Leo Sternbach at Hoffmann-La Roche and was launched in 1960. The second active ingredient, the well-known diazepam (Valium), was launched in 1962. Numerous other drugs followed (see below).
Structure and properties
Benzodiazepines are substituted derivatives of a 5-aryl-1,4-diazepine fused to a benzene ring. With the exception of clobazam, they are 1,4-benzodiazepines; clobazam is a 1,5-benzodiazepine. Some agents are fused to a heterocycle, e.g., midazolam to an imidazole or triazolam to a triazole.
Effects
Benzodiazepines (ATC N05BA) have antianxiety, sedative, sleep-inducing, anticonvulsant (antiepileptic), and muscle relaxant properties. The effects are due to allosteric binding to the postsynaptic GABAA receptor, the opening of chloride channels, and the enhancement of the effects of GABA, the major inhibitory neurotransmitter in the brain.
Indications
- Anxiety, agitation and tension states, panic.
- Psychosomatic disorders
- Epilepsy
- Muscle spasms
- Sleep disturbances
- For anesthesia, as a sedative before surgical or diagnostic procedures.
Dosage
According to the professional information. Actually, the duration of therapy should usually be kept as short as possible and not exceed one to three months. In practice, however, benzodiazepines are often used for months to years. We estimate that tens of thousands of patients in many countries are dependent on the drugs.
Active ingredients
- Alprazolam (Xanax)
- Bromazepam (Lexotanil)
- Chlordiazepoxide (Librium)
- Clobazam (Urbanyl)
- Clonazepam (Rivotril)
- Clorazepate (Tranxillium)
- Cloxazolam (out of trade)
- Delorazepam (EN)
- Diazepam (Valium, Stesolid), diazepam nasal spray.
- Estazolam (not commercially available)
- Flunitrazepam (Rohypnol)
- Flurazepam (Dalmadorm)
- Halazepam (Pacinone)
- Ketazolam (Solatran)
- Lorazepam (Temesta)
- Lormetazepam (Loramet, Noctamide).
- Medazepam (Rudotel, D).
- Midazolam (Dormicum), midazolam nasal spray.
- Nitrazepam (Mogadon)
- Oxazepam (Seresta, Anxiolite)
- Prazepam (Demetrin)
- Temazepam (Normison)
- Tetrazepam (not commercially available in many countries).
- Triazolam (Halcion)
Flumazenil (Anexate) is an antidote that can be used to reverse the effects of benzodiazepines, for example in the case of an overdose. The typical endings of the benzodiazepines are -azepam and -azolam.
Abuse
Benzodiazepines can be abused as depressant intoxicants and become addictive. Abuse is dangerous, especially in combination with other depressant and respiratory depressant drugs and with alcohol. Many celebrities are said to have benzodiazepine (over)use. For example, according to an autopsy report, actor Heath Ledger (, ) died from a drug cocktail that contained the three benzodiazepines diazepam, temazepam and alprazolam, in addition to opioids and doxylamine. Benzodiazepines such as flunitrazepam (Rohypnol) are also abused as so-called “date rape drugs” see under flunitrazepam.
Contraindications
Benzodiazepines are contraindicated in hypersensitivity; severe respiratory failure; sleep apnea syndrome; myasthenia gravis; dependence on medications, intoxicants, or alcohol; and during pregnancy and lactation. For complete precautions, see the drug label.
Interactions
Many benzodiazepines are metabolized by CYP450, and corresponding drug interactions with CYP inhibitors and inducers are possible. Other interactions are observed with central depressant drugs, alcohol, and muscle relaxants.
Adverse effects
Possible adverse effects include:
- Psychiatric disorders and paradoxical reactions: Restlessness, agitation, irritability, aggressiveness, delusions, outbursts of anger, nightmares, hallucinations, psychosis, triggering of depression.
- Central disorders: Fatigue, drowsiness, dullness, impaired responsiveness, dizziness, headache, anterograde amnesia, memory impairment.
- Visual disturbances: Double vision, blurred vision
- Respiratory disorders, respiratory depression
- Digestive disorders: Dry mouth, nausea, vomiting, diarrhea, constipation.
- Muscle weakness, ataxia, risk of falls, especially in the elderly.
- Cardiovascular disorders: Low blood pressure
- Development of tolerance, increase in dose
- Severe skin reactions (tetrazepam).
With rapid discontinuation, withdrawal symptoms may occur. All benzodiazepines can be psychologically and physically addictive and can cause withdrawal symptoms if discontinued quickly.
