Chlordiazepoxide is an anxiolytic drug from the benzodiazepine group. He was the first representative of tranquilizers in this group. Currently, it includes a number of more effective drugs, but chlordiazepoxide has not completely lost its value.
Chlordiazepoxide | |
---|---|
Chlordiazepoxide | |
Chemical compound | |
IUPAC | 7- chloro -2-methylamino-5- phenyl- 3H-1,4- benzodiazepine- 4-oxide |
Gross formula | C 16 H 14 ClN 3 O |
Molar mass | 299.08 |
CAS | |
Pubchem | |
Drugbank | |
Classification | |
Pharmacol. Group | Tranquilizer |
ATH | |
Pharmacokinetics | |
Metabolism | in the liver |
The period is half out. | 5β30 hours |
Excretion | by the kidneys |
Dosage Forms | |
tablets , capsules , 5 mg , 10 mg and 25 mg tablets | |
Other names | |
Elenium, Librium | |
Content
Pharmacodynamics
Chlordiazepoxide enhances the inhibitory effect of GABA (a mediator of pre- and postsynaptic inhibition in all parts of the CNS) on the transmission of nerve impulses . Stimulates the benzodiazepine zones located in the allosteric center of the postsynaptic GABA receptors of the ascending activating reticular formation of the brain stem and the intercalary neurons of the lateral horns of the spinal cord ; reduces the excitability of the subcortical structures of the brain (limbic system, thalamus , hypothalamus ), inhibits polysynaptic spinal reflexes .
Anxiolytic effect is due to the effect on the almond-shaped complex of the limbic system and is manifested in the reduction of emotional stress, easing anxiety, fear , anxiety.
Sedation is due to the effect on the reticular formation of the brain stem and nonspecific thalamic nuclei and is manifested by a decrease in the symptoms of neurotic origin (anxiety, fear ). It has a pronounced sedative effect. The main mechanism of the hypnotic action is the inhibition of the cells of the reticular formation of the brain stem .
Reduces the impact of emotional, vegetative and motor stimuli that violate the mechanism of falling asleep. In the first 3-5 days of admission, it may have a moderate hypnotic effect (facilitates falling asleep), and also slightly reduce blood pressure.
It causes moderate muscle relaxation , has a weak anti-epileptic effect .
The central muscle relaxant effect is due to the inhibition of polysynaptic spinal afferent inhibitory pathways (to a lesser extent and monosynaptic). Direct inhibition of motor nerves and muscle function is also possible.
Anticonvulsant action is implemented by enhancing presynaptic inhibition. The spread of epileptic activity is suppressed, but the excited state of the focus is not removed.
It inhibits central sympathetic influences, has antiarrhythmic effect . It causes relaxation of the muscles of the uterus , has antihypoxic properties (including myocardial infarction ).
Pharmacokinetics
Pharmacokinetic hlozepid (like other tranquilizers of this series) is characterized by relatively rapid absorbability after ingestion. The peak concentration in the blood plasma is observed in 2-4 hours; elimination half-life of 8-10 hours. It is allocated mainly by kidneys. It penetrates the placental barrier.
Dosing
- It is administered orally (by mouth), for adults - 5β25 mg 3β4 times a day, for debilitated patients and elderly patients - 5β10 mg 2β4 times a day, if necessary, taking into account tolerance, the dose gradually increases.
- With a state of tension and anxiety, combined with insomnia, 10-20 mg 1 time for 1-2 hours before sleep.
- In psychiatric practice, initially 50β100 mg / day, then the dose gradually rises to 300 mg / day, which is divided into 3-4 doses.
- Premedication - 5-10 mg 3-4 times a day, starting 1 day before surgery.
- Alcohol withdrawal - an initial dose of 50-100 mg, if necessary, repeat in the same dose in 2-4 hours, the maximum dose of 400 mg / day, then reduce the dose to a maintenance level.
- Children aged 6-7 years - 5-10 mg / day, 8-14 years - 10-20 mg / day, 15-18 years - 20-30 mg / day.
The daily dose is always divided into 3-4 single doses.
Indications
Neurosis, psychopathy (with irritability, psychogenic stupor); stress, anxiety in psychosomatic diseases, endogenous psychosis (auxiliary drugs), anxiety, accompanying diseases of internal organs, stress, neurotic headache, cardialgia, causalgia , hysterical state, reactive depression, sleep disorders, convulsions, rheumatic and neurotic hyperkinesis, menopausal and premenstrual syndromes, tremor (senile, essential).
In anesthesia practice can be used for preoperative sedation of patients, introductory general anesthesia and in the postoperative period.
In connection with the ability to lower muscle tone, they are also used in spastic conditions (for example, facial hemispasm) associated with brain and spinal cord lesions (including with movement disorders in children), as well as with myositis, arthritis, bursitis, radiculitis and other diseases accompanied by muscle tension.
Appoint also with eczema and other skin diseases, accompanied by itching , irritability.
In psychiatric practice, hlozepid is sometimes used in borderline states with obsession, anxiety, fear, affective tension, in shallow depressive and hypochondriacal states, including those associated with diencephalic pathology, as well as in complex treatment of patients with epilepsy and for the treatment of withdrawal syndrome in alcoholism and addiction.
Contraindications
Hypersensitivity, porphyria , acute alcohol intoxication with the weakening of vital functions, acute intoxication of drugs that have a depressing effect on the central nervous system (including narcotic analgesics and hypnotics drugs), myasthenia gravis, shock, angle-angle glaucoma (acute attack or predisposition), severe X, shock, severe glaucoma (acute attack or predisposition), severe X or degrees of respiratory failure), severe depression (suicidal tendencies may occur), pregnancy (especially I trimester), lactation, age up to 6 years (safety and efficacy of n defined). The drug should not be taken during and on the eve of work by transport drivers and other persons whose work requires a quick mental and physical reaction.
C is used with caution in hyperkinesia, hypoproteinemia (and diseases leading to its development), organic brain diseases, bronchospastic syndrome, renal and / or liver failure, cerebral and spinal ataxia, drug addiction in history, propensity to abuse psychoactive drugs, psychosis paradoxical intensification of symptoms is possible), violation of swallowing in children, nocturnal sleep apnea (established or suspected), in old age.
Side
Chlozepid is usually well tolerated. However, the following side effects are possible:
- The nervous system
At the beginning of treatment (especially in elderly patients) - drowsiness, fatigue, dizziness, decreased ability to concentrate, ataxia, lethargy, dulling of emotions, slowing down of mental and motor responses; rarely - headache, euphoria, depression, tremor, loss of memory, depressed mood, confusion, dystonic extrapyramidal reactions (uncontrolled body movements, including eyes), asthenia, myasthenia gravis, dysarthria; extremely rarely - paradoxical reactions (aggressive outbursts, confusion, hallucinations, acute agitation, irritability, anxiety, insomnia).
- From the side of blood formation organs
Leukopenia, neutropenia, agranulocytosis ( chills , hyperthermia, sore throat , excessive fatigue or weakness), anemia, thrombocytopenia, accompanied by increased bleeding.
- Since the cardiovascular system
When taken in large doses - lowering blood pressure, tachycardia, palpitations.
- From the digestive system
Dry mouth or drooling, heartburn, nausea, vomiting, loss of appetite, intestinal colic, intestinal motility disorders (constipation or diarrhea); biliary dyskinesia, liver dysfunction, increased activity of liver transaminases and alkaline phosphatase, jaundice.
- On the part of the respiratory system
Difficulty breathing, bronchorea, bronchospasm.
- From the genitourinary system
Incontinence, urinary retention, impaired renal function, increased or decreased libido, dysmenorrhea.
- Allergic reactions
Skin rash, itching, drug lupus erythematosus.
- Impact on the fetus
Teratogenicity (especially I trimester), central nervous system depression, respiratory failure and suppression of the sucking reflex in newborns whose mothers used the drug.
- Other
Addiction, drug addiction; rarely - visual impairment (diplopia), weight loss, anterograde amnesia; with a sharp decrease in dose or termination of admission - βwithdrawal syndromeβ (irritability, nervousness, sleep disturbances, dysphoria, smooth muscle spasm of internal organs and skeletal muscles, depersonalization, increased sweating, depression, nausea, vomiting, tremor, perception disorders, including hyperacusia , paresthesia, photophobia , tachycardia, convulsions, rarely - acute psychosis).
Overdose
Symptoms
When taken from 500-600 mg drowsiness, confusion, paradoxical arousal, decreased reflexes, dysarthria, ataxia, nystagmus, tremor, bradycardia, shortness of breath or difficulty breathing, severe weakness, lowering blood pressure, depression of cardiac and respiratory activity, coma.
Treatment
Immediate gastric lavage, reception of activated carbon, intravenous injection of physostigmine salicylate or a specific benzodiazepine receptor antagonist flumazenil, symptomatic therapy (maintaining breathing and blood pressure). Hemodialysis is ineffective.
Special instructions
In the process of treating patients, it is strictly forbidden to use ethanol. With long-term treatment, control of the pattern of peripheral blood and the activity of βliverβ enzymes is necessary. Particular caution is required when using chlordiazepoxide, especially at the beginning of treatment, in patients who have long received centrally acting antihypertensive drugs, beta-blockers, anticoagulants, cardiac glycosides (the degree and mechanisms of drug interaction are unpredictable). The risk of drug dependence formation increases with the use of large doses, a significant duration of treatment (more than 1 month) in patients previously abusing ethanol or drugs. Without special instructions should not be used for a long time.
It is necessary to cancel the drug gradually, abrupt cancellation is accompanied by a syndrome of "cancel" (headache, myalgia, anxiety, tension, confusion, irritability; in severe cases, derealization, depersonalization, hyperacusia, paresthesia in the extremities, light and tactile hypersensitivity; hallucinations and epileptic seizures ). The abolition of the drug should be carried out gradually. If patients experience such unusual reactions as increased aggressiveness, acute states of arousal, fear, thoughts of suicide, hallucinations, increased muscle cramps, difficult falling asleep, and shallow sleep, treatment should be stopped.
During pregnancy, apply only in exceptional cases and only for health reasons. It has a toxic effect on the fetus and increases the risk of congenital malformations when used in the first trimester of pregnancy. Taking therapeutic doses in the later stages of pregnancy can cause depression of the central nervous system of the newborn. Constant use during pregnancy can lead to physical dependence with the development of the syndrome of "cancellation" in the newborn. Children, especially at a younger age, are very sensitive to benzodiazepine-depressing central nervous system effects. Use immediately before or during childbirth can cause respiratory depression in the newborn, decreased muscle tone, hypotension, hypothermia, and a weak act of sucking (βsluggish babyβ syndrome).
During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and psychomotor speed.
Interaction
Antipsychotic drugs (neuroleptics), hypnotic drugs, tricyclic antidepressants, narcotic analgesics, drugs for general anesthesia, muscle relaxants and ethanol increase the sedative effect. Inhibitors of microsomal oxidation (cimetidine, disulfiram, oral contraceptives) increase the concentration and lengthen the effect of the drug (due to inhibition of hepatic metabolism). Inductors of liver microsomal enzymes reduce efficacy (phenobarbital and phenytoin accelerate chlordiazepoxide metabolism). Narcotic analgesics increase euphoria, leading to an increase in drug dependence. Antacids reduce the rate (but not completeness of absorption) of chlordiazepoxide (C SS , arising from long-term use of these drugs, does not change). Hypotensive drugs can increase the severity of blood pressure reduction. Against the background of the simultaneous appointment of clozapine may increase respiratory depression. May increase zidovudine toxicity. Theophylline, used in small doses, distorts the sedative effect of chlordiazepoxide. Reduces the effectiveness of levodopa in patients with parkinsonism. In rare cases, chlordiazepoxide suppresses metabolism and enhances the effect of phenytoin.
Monoamine oxidase inhibitors and phenothiazine derivatives should not be given at the same time.
Physical Properties
White or light yellow crystalline powder. Practically insoluble in water, difficult to dissolve in alcohol.
Commercial Names
In Western countries, produced under the name "Librium". In Poland, produced under the name "Elenium" [1]
- β [Cherkes A.I., Melnikova V.F. Manual on pharmacotherapy. - Ed. 2nd, rev. and add. - Kiev: Health, 1970. - p. 354