Benzodiazepines are special chemical compounds (compounds of a benzene ring with a diazepine ring) that exert psychotropic effects in the body. They are used in medicine as antianxiety (anxiolytic), central-muscle-relaxant, sedative, and sleep-inducing (hypnotic) drugs. The anticonvulsant (anticonvulsant) effects of some benzodiazepines also explain their use as antiepileptic drugs.
What are benzodiazepines?
All benzodiazepines are derivatives of the same basic chemical structure. This is a bicyclic ring system of benzene and diazepine rings. The benzene ring is the simplest representative of the benzoid aromatic hydrocarbons with the molecular formula: C6H6. A diazepine ring is fused to it (connected by condensation). The diazepine ring is a seven-membered, unsaturated ring with 2 nitrogen atoms. Diazepine rings with nitrogen atoms at the 1st and 4th position in the ring – so-called benzo-1,4-diazpines – are predominantly used as drugs. At the 5th position of the diazepine ring, another six-membered ring is connected, but not by an annealing. Different binding sites in the benzene ring region, on the diazepine ring, and on the additional six-membered ring result in different active ingredients, some with different effects.
Pharmacological action
Benzodiazepines have an activating effect at gamma-amino-butyric acid (GABA) receptor A by binding, thereby increasing the action of the neurotransmitter GABA. GABA-A receptors are found distributed throughout the brain and spinal cord. Binding increases the opening probability of the GABA-A receptor, resulting in increased chloride influx into the neuron. This hyperpolarizes the neuron membrane, resulting in decreased excitability. The GABA-A receptor consists of 6 subunits, with classical benzodiazepines showing affinity for 4 of these subunits (alpha1, alpha2, alpha3, and alpha5). An effect at the receptor is only possible in the presence of the neurotransmitter GABA together – they are therefore allosteric modulators and not agonists in the narrower sense. The effect is stronger at those synapses that contain little GABA. The effect is activity-dependent. This means that weak transmitter responses are disproportionately enhanced. This could also be responsible for the specific effect of benzodiazepines. Benzodiazepines act in the human body:
- Anxiety-relieving (anxiolytic).
- Anticonvulsant (anticonvulsant)
- Muscle relaxing (muscle relaxant)
- Calming (sedative)
- Sleep-inducing (hypnotic)
- Amnesic (memory gap during the duration of action).
- Slightly mood-boosting (note: if there is an existing underlying depressive disorder, this may also be amplified).
- Partially euphoric (dose-dependent and dependent on the intake interval).
High doses of benzodiazepines do not increase the maximum effect. However, there is a reduction in the necessary dose of GABA to trigger the maximum effect. Thus, the dose-response curve of gamma-amino-butyric acid is shifted to the left.
Medical application and use
Because of the effects that can be achieved, benzodiazepines are used primarily in emergency medicine and in psychiatry. However, the possible areas of application are significantly limited due to the high dependence potential as well as the strong respiratory depressive side effects. Regular use of benzodiazepines from about 8 weeks onwards leads to withdrawal symptoms when the drug is discontinued. It is therefore recommended that benzodiazepines should not be used for longer than 4 weeks (assuming a strict indication and as low a dosage as possible). The antiepileptic benzodiazepines, which often have to be taken for life, are an exception. The active ingredients diazepam and lorazepam are particularly suitable as first-line agents for the treatment of acute epileptic seizures. In psychiatry, benzodiazepines are used primarily in the treatment of anxiety and agitation. They are also frequently used as acute medications for panic attacks. Benzodiazepines also have a firm place in the treatment of alcohol withdrawal symptoms. Benzodiazepines can also be used in the short-term treatment of sleep onset and sleep maintenance disorders. However, due to their dependence potential, other substance groups (such as antihistamines) are increasingly preferred.In emergency medicine, benzodiazepines are also used in the induction of anesthesia and as part of pain therapy (analgesia). In selective surgery, premedication before surgery is often with a benzodiazepine such as midazolam to relieve the patient’s tension and possible anxiety before the procedure.
Risks and side effects
Benzodiazepines have varying degrees of respiratory depression by depressing the respiratory center in the medulla oblongata. Although respiratory depression occurs in a dose-dependent manner, life-threatening intoxications from benzodiazepines alone are rare. However, especially in mixed intoxications together with alcohol or other CNS-active drugs (for example, opiates), there is a markedly increased risk of fatal respiratory arrest. The interaction between benzodiazepines and alcohol is referred to as cross-tolerance because of the similar effect on the GABA-A receptor. Thus, the often-practiced dose increase in response to increased tolerance leads to increased side effects. The addictive potential of benzodiazepines is evident in the severe physical dependence that occurs even at therapeutic doses. It is therefore not surprising that benzodiazepines have the highest abuse rates worldwide. The medication then leads to disturbances in memory function, behavioral disorders, psychomotor slowing, and paradoxical effects (increase in anxiety and/or sleep disorders). Contraindications to taking benzodiazepines include:
- Myasthenia gravis (disorder of neuromuscular transmission of excitation).
- Ataxia (disorder of movement coordination).
- Narrow-angle glaucoma (glaucoma)
- Existing addictive disease (also in the history).
- Allergy to the active substance
- Sleep apnea syndrome (breathing pauses during sleep).
