BENZODIAZEPINES (BZDs) Uses, Side Effects, and More

 BENZODIAZEPINES ( BZDs)

BRAND NAME:-  No specific brand available

BENZODIAZEPINES (BZDs) in addition to prea aesthetic medication,BNZs are now frequently used for including, maintaining and supplementing anaesthesia as well as for ' conscious sedation ' . 

PHARMACODYNAMIC:-  

UNKNOWN.

PHARMACOLOGICAL ACTION:- 

The weak antiemetic property of BZDs is primarily based on the sedative action. 

Benzodiazepines work by increasing the effectiveness of the endogenous chemical, GABA, to decrease the excitability of neurons.This reduces the communication between neurons and, therefore, has a calming effect on many of the functions of the brain.

GABA controls the excitability of neurons by binding to the GABA  receptor. The GABAa receptor is a protein complex located in the synapses between neurons. All GABAa receptors contain an ion channel that conducts chloride ions across neuronal cell membranes and two binding sites for the neurotransmitter gamma-aminobutyric acid (GABA), while a subset of GABAa receptor complexes also contain a single binding site for benzodiazepines. Binding of benzodiazepines to this receptor complex does not alter binding of GABA. Unlike other positive allosteric modulators that increase ligand binding, benzodiazepine binding acts as a positive allosteric modulator by increasing the total conduction of chloride ions across the neuronal cell membrane when GABA is already bound to its receptor. This increased chloride ion influx hyperpolarizes the neuron's membrane potential. As a result, the difference between resting potential and threshold potential is increased and firing is less likely. Different GABAa receptor subtypes have varying distributions within different regions of the brain and, therefore, control distinct neuronal circuits. Hence, activation of different GABAA receptor subtypes by benzodiazepines may result in distinct pharmacological actions.In terms of the mechanism of action of benzodiazepines, their similarities are too great to separate them into individual categories such as anxiolytic or hypnotic. For example, a hypnotic administered in low doses produces anxiety-relieving effects, whereas a benzodiazepine marketed as an anti-anxiety drug at higher doses induces sleep.

The subset of GABAa receptors that also bind benzodiazepines are referred to as benzodiazepine receptors (BzR). The GABAa  receptor is a heteromer composed of five subunits, the most common ones being two αs, two βs, and one γ (α2β2γ1). For each subunit, many subtypes exist (α1–6, β1–3, and γ1–3). GABAA receptors that are made up of different combinations of subunit subtypes have different properties, different distributions in the brain and different activities relative to pharmacological and clinical effects.Benzodiazepines bind at the interface of the α and γ subunits on the GABAa receptor. Binding also requires that alpha subunits contain a histidine amino acid residue, (i.e., α1, α2, α3, and α5 containing GABAa  receptors). For this reason, benzodiazepines show no affinity for GABAa receptors containing α4 and α6 subunits with an arginine instead of a histidine residue.Once bound to the benzodiazepine receptor, the benzodiazepine ligand locks the benzodiazepine receptor into a conformation in which it has a greater affinity for the GABA neurotransmitter. This increases the frequency of the opening of the associated chloride ion channel and hyperpolarizes the membrane of the associated neuron. The inhibitory effect of the available GABA is potentiated, leading to sedative and anxiolytic effects. For instance, those ligands with high activity at the α1 are associated with stronger hypnotic effects, whereas those with higher affinity for GABAa receptors containing α2 and/or α3 subunits have good anti-anxiety activity.

GABAA receptors participate in the regulation of synaptic pruning by prompting microglial spine engulfment. Benzodiazepines have been shown to upregulate microglial spine engulfment and prompt overzealous eradication of synaptic connections. This mechanism may help explain the increased risk of dementia associated with long-term benzodiazepine treatment.

The benzodiazepine class of drugs also interact with peripheral benzodiazepine receptors. Peripheral benzodiazepine receptors are present in peripheral nervous system tissues, glial cells, and to a lesser extent the central nervous system.These peripheral receptors are not structurally related or coupled to GABAa receptors. They modulate the immune system and are involved in the body response to injury. Benzodiazepines also function as weak adenosine reuptake inhibitors. It has been suggested that some of their anticonvulsant, anxiolytic, and muscle relaxant effects may be in part mediated by this action.Benzodiazepines have binding sites in the periphery, however their effects on muscle tone is not mediated through these peripheral receptors. The peripheral binding sites for benzodiazepines are present in immune cells and gastrointestinal tract. 

MECHANISM OF ACTION:-

Benzodiazepines are a group of CNS depressants which induce feelings of calm (anxiolysis), drowsiness and sleep. They act by facilitating the binding of the inhibitory neurotransmitter GABA at various GABA receptors throughout the CNS. 

USED:-  

Benzodiazepines may be used to treat:

alcohol withdrawal

anxiety

as a muscle relaxant

panic disorder

seizures

sleep disorders

to induce relaxation and cause amnesia prior to surgical operations. 

SIDE EFFECTS:-  

sedation,

dizziness,

weakness, and

unsteadiness.

DOSE:-  0.5 -2 mg i.v. , as directed by physician.