Chlordiasepoxide is a derivative of benzodiazepine. Chlordiasepoxide affects many structures of the central nervous system, primarily the hypothalamus and limbic system, that is, structures that are associated with the regulation of emotional activity. Chlordiasepoxide interacts with specific benzodiazepine receptors, which are located in the post-synaptic GABAA-receptor complex in the amygdala nucleus, cerebral cortex, striate body, hippocampus, cerebellum, podburnum, spinal cord. Chlordiasepoxide, like other benzodiazepines, increases the inhibitory effect of GABAergic cortical neurons, hypothalamus, thalamus. For benzodiazepines, including chlordiazepoxide, there are specific binding sites, which are protein structures of cell membrane and have a connection with the complex, which consists of a chlorine channel and GABAA-A receptor. Chlordiasepoxide modulates the sensitivity of the GABAAergic receptor and increases the affinity of the receptor to gamma-aminobutyric acid, which is a inhibitory endogenous neurotransmitter. As a result of activation of GABAA or benzodiazepine receptor, there is increased transport of chlorine ions into the neuron through the chlorine channel, which leads to hyperpolarization of cell membrane and suppression of neuron activity. Chlorodiazepoxide blocks polysynaptic reflexes. Chlordiasepoxide clinically has a sedative, anxiolytic, moderate sleeping effect, has anticonvulsant effect, reduces the tone of skeletal muscles. Chlordiasepoxide has a pronounced soothing effect on the central nervous system. Chlordiasepoxide suppresses excitement, anxiety, emotional stress. Chlordiazepoxide reduces fears and obsessions, increases susceptibility to hypno-suggetic treatment. Chlordiasepoxide relieves tremor, has antipanic effect, has a weak anticonvulsant effect.
Chlordiasepoxide reduces the severity of fear and anxiety, which are associated with the upcoming surgery. In large doses, chlordiasepoxide can reduce psychomotor agitation. Chlordiasepoxide causes moderate muscle relaxation. Chlordiasepoxide has a moderate sleeping effect, usually expressed in the first 3 – 5 days of treatment, then a positive effect on sleep due to the elimination of various psychogenic irritants. Chlordiazepoxide has a mild analgesic effect, increases appetite. Relieves symptoms of acute alcohol withdrawal, such as nervous tension, anxiety, agitation, anxiety tremor and others.
Chlordiaseepoxide has a high lipophilicity and is almost completely absorbed after ingestion. The starting time and absorption rate of chlordiazepoxide can be varied. At a single oral intake of 15 – 25 mg of chlordiazepoxide suction occurs within 35 – 45 minutes. Absorption slows down the absorption of food. The maximum concentration of chlordiazepoxide in plasma is reached after 0.5 to 4 hours. Chlordiasepoxide binds to plasma proteins by 96 %. The equilibrium chlordiazepoxide concentration is reached after 5 – 12 days from the beginning of therapy. Chlordiazepoxide penetrates the hematoencephalic and placental barrier and is excreted with breast milk. Chlordiasepoxide Contraindications is slowly absorbed from muscle tissue. Chlordiasepoxide is metabolized in the liver by oxidation, N-demethylation, decomposition, hydroxylation with further glucuronation, and pharmacologically active metabolites (desmethylchlordiasepoxide, oxazepam, demoxepam, desmethyldiazepam) are formed. The half-life of chlordiazepoxide is 5 – 30 hours, its metabolites: oxazepam – 5 – 15 hours, desmethylchlordiasepoxide – 8 – 24 hours, demoxepam – 14 – 95 hours, desmethyldiazepam – 30 – 100 hours. Chlordiasepoxide is eliminated by kidneys (1-2% – in its unchanged form, 3-6% is eliminated in a related form). Chlordiasepoxide is cumulated (especially in elderly patients and in liver function disorders). Chlordiasepoxide refers to benzodiazepines with a long period of half-life, excretion after cancellation of chlordiasepoxide therapy is slow, because the metabolites remain in the blood for several days or even weeks. The accumulation of chlordiazepoxide and its active metabolites at repeated use is significant.
In elderly patients, the half-life of chlordiazepoxide is 60% longer than in young patients, while the overall clearance of chlordiazepoxide in elderly patients remains unchanged, as the lengthening of the half-life is balanced by an increase in the volume of distribution observed at this age. In older patients, chlordiazepoxide absorption and metabolism are slower. In cirrhosis of the liver, the clearance of chlordiazepoxide decreases, as the drug has a pronounced liver metabolism, so dose correction is necessary. Metabolic transformations are significantly slowed down in liver damage.