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d what is known as the benzodiazepine withdrawal syndrome withdrawal from chlordiazepoxide or other benzodiazepines often leads to withdrawal symptoms that are similar to those seen with alcohol and barbiturates the higher the dose and the longer the drug is taken the risk of experiencing unpleasant withdrawal symptoms becomes greater withdrawal symptoms can however occur at standard dosages and also after short term use benzodiazepine treatment should be discontinued as soon as possible through a slow and gradual dose reduction regime 22 chlordiazepoxide taken during pregnancy can cause a postnatal benzodiazepine withdrawal syndrome 23 overdose edit see also benzodiazepine overdose an individual who has consumed excess chlordiazepoxide may display some of the following symptoms somnolence difficulty staying awake mental confusion hypotension hypoventilation impaired motor functions impaired reflexes impaired coordination impaired balance dizziness muscle weakness coma chlordiazepoxide is typically used under controlled conditions for specific syndromes and sees far less frequent usage when compared to newer drugs of the same class and thus is unlikely to be encountered in a clinical emergency setting as a stand alone drug causing life threatening concern like other drugs in its class chlordiazepoxide alongside benzodiazepines as a whole have a lowered potential to cause life threatening injury though this does not preclude their common co contaminant discovery with other depressant drugs of abuse nor their ability to contribute to an already potentially fatal episode of drug induced respiratory depression in cases of suspected overdose supportive care and observation are most often indicated and provided incrementally in relation to severity and duration of symptoms flumazenil is uniquely poised as an antidote that specifically counteracts damaging central nervous system affect induced via benzodiazepine mechanism of action though is not generally indicated in relation to the severity of symptoms where other treatment options exist and often has numerous damaging consequences that must be carefully weighted before any potential administration 24 pharmacology edit chlordiazepoxide acts on benzodiazepine allosteric sites that are part of the gaba a receptor ion channel complex and this results in an increased binding of the inhibitory neurotransmitter gaba to the gaba a receptor thereby producing inhibitory effects on the central nervous system and body similar to the effects of other benzodiazepines 25 chlordiazepoxide is an anticonvulsant 26 chlordiazepoxide is preferentially stored in some organs including the hearts of neonates absorption by any administered route and the risk of accumulation is significantly higher in neonates the withdrawal of chlordiazepoxide during pregnancy and breast feeding is recommended as chlordiazepoxide rapidly crosses the placenta and also is excreted in breast milk 27 chlordiazepoxide also decreases prolactin release in rats 28 benzodiazepines act via micromolar benzodiazepine binding sites as ca2 channel blockers and significantly inhibit depolarization sensitive calcium uptake in animal nerve terminal preparations 29 chlordiazepoxide inhibits acetylcholine release in mouse hippocampal synaptosomes in vivo this has been found by measuring sodium dependent high affinity choline uptake in vitro after pretreatment of the mice in vivo with chlordiazepoxide this may play a role in chlordiazepoxide s anticonvulsant properties 30 pharmacokinetics edit chlordiazepoxide is a long acting benzodiazepine drug the half life of chlordiazepoxide is from 5 to 30 hours but has an active benzodiazepine metabolite nordiazepam which has a half life of 36 to 200 hours 31 the half life of chlordiazepoxide increases significantly in the elderly which may result in prolonged action as well as accumulation of the drug during repeated administration delayed body clearance of the long half life active metabolite also occurs in those over 60 years of age which further prolongs the effects of the drugs with additional accumulation after repeated dosing 32 despite its name chlordiazepoxide is not an epoxide history edit chlordiazepoxide initially called methaminodiazepoxide was the first benzodiazepine to be synthesized in the mid 1950s the synthesis was derived from work on a class of dyes quinazoline 3 oxides 33 it was discovered by accident when in 1957 tests revealed that the compound had hypnotic anxiolytic and muscle relaxant effects the story of the chemical development of librium and valium was told by sternbach the serendipity involved in the invention of this class of compounds was matched by the trials and errors of the pharmacologists in the discovery of the tranquilizing activity of the benzodiazepines the discovery of librium in 1957 was due largely to the dedicated work and observational ability of a gifted technician beryl kappell for some seven years she had been screening compounds by simple animal tests for muscle relaxant activity using myanesin as a standard and then meprobamate and chlorpromazine when they became available all compounds submitted by the chemical staff for central nervous activity were screened it was this battery of tests that picked out ro 5 0690 librium chlordiazepoxide as being similar but more potent than meprobamate 34 three years later chlordiazepoxide was marketed as a therapeutic benzodiazepine medication under the brand name librium following chlordiazepoxide in 1963 diazepam hit the market under the brand name valium and was followed by many further benzodiazepine compounds over the subsequent years and decades 35 in 1959 it was used by over 2 000 physicians and more than 20 000 patients it was described as chemically and clinically different from any of the tranquilizers psychic energizers or other psychotherapeutic drugs now available during studies chlordiazepoxide induced muscle relaxation and a quieting effect on laboratory animals like mice rats cats and dogs fear and aggression were eliminated in much smaller doses than those necessary to produce hypnosis chlordiazepoxide is similar to phenobarbital in its anticonvulsant properties however it lacks the hypnotic effects of barbiturates animal tests were conducted in the boston zoo and the san diego zoo forty two hospital patients admitted for acute and chronic alcoholism and various psychoses and neuroses were treated with chlordiazepoxide in a majority of the patients anxiety tension and motor excitement were effectively reduced the most positive results were observed among alcoholic patients it was reported that ulcers and dermatologic problems both of which involved emotional factors were reduced by chlordiazepoxide 36 in 1963 approval for use was given to diazepam valium a simplified version of chlordiazepoxide primarily to counteract anxiety symptoms sleep related problems were treated with nitrazepam mogadon which was introduced in 1972 temazepam restoril which was introduced in 1979 and flurazepam dalmane which was introduced in 1975 37 recreational use edit see also benzodiazepine drug misuse in 1963 carl f essig of the addiction research center of the national institute of mental health stated that meprobamate glutethimide ethinamate ethchlorvynol methyprylon and chlordiazepoxide were drugs whose usefulness can hardly be questioned however essig labeled these newer products as drugs of addiction like barbiturates whose habit forming qualities were more widely known he mentioned a 90 day study of chlordiazepoxide which concluded that the automobile accident rate among 68 users was 10 times higher than normal participants daily dosage ranged from 5 to 100 milligrams 38 chlordiazepoxide is a drug of potential misuse and is frequently detected in urine samples of drug users who have not been prescribed the drug 39 legal status edit internationally chlordiazepoxide is a schedule iv controlled drug under the convention on psychotropic substances 40 toxicity edit animal edit laboratory tests assessing the toxicity of chlordiazepoxide nitrazepam and diazepam on mice spermatozoa found that chlordiazepoxide produced toxicities in sperm including abnormalities involving both the shape and size of the sperm head nitrazepam however caused more profound abnormalities than chlordiazepoxide 41 society and culture edit chlordiazepoxide is the drug referenced in the netflix series the queen s gambit under the commercial name librium 42 it also appears prominently in the hbo series the pitt in infinite jest by david foster wallace a nurse negotiated a trade of shoes for librium with the character tiny ewell in the first episode of yes minister jim hacker tells his wife annie to take a librium when she couldn t find a cigarette availability edit chlordiazepoxide is available in various dosage forms alone or in combination with other drugs worldwide in combination with clidinium as normaxin cc and in combination 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