Chlordiazepoxide (pronounced [ˈklɔːrˌdaɪəzepˈoksaɪd], marketed under the trade name Librium®) is a sedative/hypnotic drug which is a benzodiazepine derivative. It has a medium to long half life. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... A sedative is a substance that depresses the central nervous system (CNS), resulting in calmness, relaxation, reduction of anxiety, sleepiness, and slowed breathing, as well as slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes. ... Hypnotic drugs are a class of drugs that induce sleep, used in the treatment of severe insomnia. ... Alprazolam 2 mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ... This article is about the computer game. ...

History

See the main article benzodiazepine for the history of Librium. Alprazolam 2 mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ...

The correct IUPAC name is: 7-chloro-2(methylamine)-5-phenyl-3H-1,4-benzodiazepine-4-oxide-hydrochloride.

Pharmacology

Chlordiazepoxide acts on benzodiazepine subreceptors of the main GABA_A receptor 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.^[1] Chlordiazepoxide is anticonvulsant.^[2] There is preferential storage of chlordiazepoxide in some organs including the heart. Absorption by any administered route and the risk of accumulation is significantly increased in the neonate and there are clinical justification to recommend the withdrawal of chlordiazepoxide during pregnancy and breast feeding as chlordiazepoxide rapidly crosses the placenta and also is excreted in breast milk.^[3] Chlordiazepoxide also decreases prolactin release.^[4] Benzodiazepines act via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit depolarization-sensitive Calcium uptake.^[5] Chlordiazepoxide has been found to inhibit acetylcholine release and sodium-dependent high affinity choline uptake which may play a role in chlordiazepoxide's anticonvulsant properties.^[6] Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model... A diagram showing the CNS: 1. ... Benzodiazepine tablets The benzodiazepines are a class of drugs with hypnotic, anxiolytic, anticonvulsant, amnestic and muscle relaxant properties. ... The anticonvulsants, sometimes also called antiepileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. ... The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. ... Choline is an organic compound, classified as an essential nutrient and usually grouped within the Vitamin B complex. ... The anticonvulsants, sometimes also called antiepileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. ...

Chlordiazepoxide is a long acting benzodiazepine drug. The half life of Chlordiazepoxide is 5-30 hours but has an active benzodiazepine metabolite which has a half life of 36 - 200 hours.^[7] 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.^[8]

Tolerance

Chronic use of benzodiazepines, such as chlordiazepoxide leads to the development of tolerance with a decrease in number of benzodiazepine binding sites.^[9]Tolerance to the anxiolytic effects develops rapidly and a stimulating effect develops after repeated daily administration.^[10] In mice tolerance to the anticonvulsant properties of chlordiazepoxide developed slowly over 15 days, although some anticonvulsant effects were still apparent after 15 days of continued administration.^[11] An anxiolytic is a drug prescribed for the treatment of symptoms of anxiety. ...

Dependence

Chlordiazepoxide can cause physical dependence, addiction and what is known as the benzodiazepine withdrawal syndrome. Withdrawal from chlordiazepoxide or other benzodiazepines often leads to withdrawal symptoms which are similar to those seen with alcohol and barbiturates. The higher the dose and the longer the drug is taken the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can however occur at standard dosages and also after short term use. Benzodiazepine treatment should be discontinued as soon as possible via a slow and gradual dose reduction regime.^[12] Physical dependence refers to a state resulting from habitual use of a drug, where negative physical withdrawal symptoms result from abrupt discontinuation. ... Heroin bottle An addiction is a recurring compulsion by an individual to engage in some specific activity, despite harmful consequences to the individuals health, mental state or social life. ... Benzodiazepine withdrawal syndrome, caused by withdrawal or dosage reduction of benzodiazepines, is the symptoms which appear when a patient who has taken the drug for a period of time stops taking the drug. ... Barbiturates are drugs that acts as central nervous system (CNS) depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. ...

The Committee on the Review of Medicines

The Committee on the Review of Medicines (UK) carried out a review into benzodiazepines due to significant concerns of tolerance, drug dependence and benzodiazepine withdrawal problems and other adverse effects. The committee found that benzodiazepines do not have any antidepressant or analgesic properties and are therefore unsuitable treatments for conditions such as depression, tension headaches and dysmenorrhoea. Benzodiazepines are also not beneficial in the treatment of psychosis. The committee also recommended against benzodiazepines being used in the treatment of anxiety or insomnia in children. The committee was in agreement with the Institute of Medicine (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the National Institute on Drug Abuse (USA) that there was little evidence that long term use of benzodiazepine hypnotics were benefitial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep promoting properties within 3 - 14 days of continuous use and in the treatment of anxiety the committee found that there was little convincing evidence that benzodiazepines retained efficacy in the treatment of anxiety after 4 months continuous use due to the development of tolerance. The committee found that the regular use of benzodiazepines caused the development of dependence characterised by tolerance to the therapeutic effects of benzodiazepines and the development of the benzodiazepine withdrawal syndrome including symptoms such as anxiety, apprehension, tremor, insomnia, nausea, and vomiting upon cessation of benzodiazepine use. Withdrawal symptoms tended to develop within 24 hours upon cessation of short acting; and 3 - 10 days after cessation of longer acting benzodiazepines. Withdrawal effects could occur after treatment lasting only 2 weeks at therapeutic dose levels however withdrawal effects tended to occur with habitual use beyond 2 weeks and were more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition. The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short term use only. It was noted in the review that alcohol can potentiate the central nervous system depressant effects of benzodiazepines and should be avoided. The central nervous system depressant effects of benzodiazepines may make driving or operating machinery dangerous and the elderly are more prone to these adverse effects. In the neonate high single doses or repeated low doses have been reported to produce hypotonia, poor sucking, and hypothermia in the neonate and irregularities in the fetal heart. Benzodiazepines should be avoided in lactation. Withdrawal from benzodiazepines should be gradual as abrupt withdrawal from high doses of benzodiazepines may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal from lower doses may cause depression, nervousness, rebound insomnia, irritability, sweating, and diarrhea.^[13] Drug addiction, or dependency is the compulsive use of drugs, to the point where the user has no effective choice but to continue use. ... Benzodiazepine withdrawal syndrome, caused by withdrawal or dosage reduction of benzodiazepines, is the symptoms which appear when a patient who has taken the drug for a period of time stops taking the drug. ... Prozac, a selective serotonin reuptake inhibitor (SSRI) Serotonin-norepinephrine reuptake inhibitor, Venlafaxine An antidepressant is a psychiatric medication or other substance (nutrient or herb) used for alleviating depression or dysthymia (milder depression). ... An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). ... Tension headaches, which were recently renamed tension type headaches by the International Headache Society, are the most common type of headaches. ... Dysmenorrhea (or dysmenorrhoea), cramps or painful menstruation, involves menstrual periods that are accompanied by either sharp, intermittent pain or dull, aching pain, usually in the pelvis or lower abdomen. ... For other uses, see Psychosis (disambiguation). ... Anxiety is a physiological state characterized by cognitive, somatic, emotional, and behavioral components (Seligman, Walker & Rosenhan, 2001). ... This article is about the sleeping disorder. ... The Institute of Medicine, a part of the National Academy of Sciences, is an American organization whose purpose is to provide national advice on issues relating to biomedical science, medicine, and health (National Academy of Sciences, n. ... Cover of a NIDA educational booklet. ... Benzodiazepine withdrawal syndrome, caused by withdrawal or dosage reduction of benzodiazepines, is the symptoms which appear when a patient who has taken the drug for a period of time stops taking the drug. ... Anxiety is a physiological state characterized by cognitive, somatic, emotional, and behavioral components (Seligman, Walker & Rosenhan, 2001). ... For the film see Tremors (film). ... This article is about the sleeping disorder. ... For other uses, see Nausea (disambiguation). ... Emesis redirects here. ... A diagram showing the CNS: 1. ... A human infant The word Infant derives from the Latin in-fans, meaning unable to speak. ... Hypotonia is a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. ... Hypothermia is a condition in which an organisms temperature drops below that Required fOr normal metabolism and Bodily functionS. In warm-blooded animals, core [[body Temperature]] is maintained nEar a constant leVel through biologic [[homEostasis]]. But wheN the body iS exposed to cold Its internal mechanismS may be unable... A human infant The word Infant derives from the Latin in-fans, meaning unable to speak. ... Fetus at eight weeks A fetus (alternatively foetus or fœtus) is an embryo in later stages of development, from the third month of pregnancy until birth in humans. ... Kittens nursing Lactation describes the secretion of milk from the mammary glands, the process of providing that milk to the young, and the period of time that a mother lactates to feed her young. ... Look up Confusion in Wiktionary, the free dictionary Confusion can have the following meanings: Unclarity or puzzlement, e. ... Psychosis (not to be confused with psychopathy) is a generic psychiatric term for a mental state in which thought and perception are severely impaired. ... This article is about the medical condition. ... For the beer, see Delirium Tremens (beer). ... Anxiety is a complex combination of the feeling of fear, apprehension and worry often accompanied by physical sensations such as palpitations, chest pain and/or shortness of breath. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... Irritability is an excessive response to stimuli. ... Perspiration (also called sweating or sometimes transpiration) is the production and evaporation of a fluid, consisting primarily of water as well as a smaller amount of sodium chloride (the main constituent of table salt), that is excreted by the sweat glands in the skin of mammals. ... Diarrhea, also spelled diarrhoea (see spelling differences), is a condition in which the sufferer has frequent watery, loose bowel movements (from the Greek word διάρροια; literally meaning through-flowing). Acute infectious diarrhea is a common cause of death in developing countries (particularly among infants), accounting for 5 to 8 million deaths...

Abuse Potential

Chlordiazepoxide is frequently detected in urine samples of drug abusers who have not been prescribed the drug suggesting a high misuse potential for chlordiazepoxide.^[14] Chlordiazepoxide in animal studies has been shown to increase reward seeking behaviours which may suggest an increased risk of addictive behavioural patterns.^[15]

Indications

Chlordiazepoxide is indicated for the short term (2 - 4 weeks) treatment of severe and distressing insomnia, anxiety and panic attacks. It has also been used as a treatment for acute alcohol or opiate withdrawal, as well as relief from Crohn's and ulcerative colitis.

Dosage

Chlordiazepoxide is available in 5mg, 10mg and 25mg strengths.

Side effects

Common side effects of chlordiazepoxide include:

• Drowsiness
• Depression
• Impaired motor function
  • Impaired coordination
  • Impaired balance
  • Dizziness
• Nervousness
• Anterograde amnesia (especially pronounced in higher doses)
• Impaired learning

Chlordiazepoxide in laboratory studies impairs latent learning. Benzodiazepines impair learning and memory via their action on benzodiazepine receptors which causes a dysfunction in the cholinergic neuronal system.^[16] In tests of various benzodiazepine compounds Chlordiazepoxide was found to cause the most profound reduction in the turnover of 5HT (serotonin). Serotonin is closely involved in regulating mood and may be one of the causes of feelings of depression in users of Chlordiazepoxide or other benzodiazepines.^[17] For other uses, see Depression. ... Many different terms are often used to describe what is collectively known as dizziness. ... Anxiety is a complex combination of the feeling of fear, apprehension and worry often accompanied by physical sensations such as palpitations, chest pain and/or shortness of breath. ... Anterograde amnesia is a form of amnesia, or memory loss, in which new events are not transferred from short-term memory to long-term memory. ... For the professional wrestling stable, see Ravens Nest#Serotonin. ...

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Contraindications

Use of chlordiazepoxide should be avoided in individuals with the following conditions:

• Myasthenia gravis
• Acute intoxication with alcohol, narcotics, or other psychoactive substances
• Ataxia
• Severe hypoventilation
• Acute narrow-angle glaucoma
• Severe liver deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of 2)
• Severe sleep apnea
• Hypersensitivity or allergy to any drug in the benzodiazepine class

Myasthenia gravis (sometimes abbreviated MG; from the Greek myastheneia, lit. ... For other uses, see Ataxia (disambiguation). ... In medicine, hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (hypo means below) to perform needed gas exchange. ... Hepatitis (plural hepatitides) implies injury to liver characterised by presence of inflammatory cells in the liver tissue. ... Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ... Sleep apnea, sleep apnoea or sleep apnœa is a sleep disorder characterized by pauses in breathing during sleep. ... Alprazolam 2 mg tablets The benzodiazepines (pronounced , or benzos for short) are a class of psychoactive drugs considered minor tranquilizers with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ...

Interactions

Oral contraceptive pills, reduce the clearance of chlordiazepoxide which may lead to increased plasma levels of chlordiazepoxide and accumulation.^[18] Chlordiazepoxide interacts with contraceptives resulting in increased bleeding.^[19]

Cannabidiol a drug with anticonvulsant properties, reduces the anticonvulsant protency of chlordiazepoxide.^[20] Cannabidiol, also known as CBD, is an antipsychotic cannabinoid found in the hemp plant Cannabis sativa. ...

Overdose

An individual who has consumed too much chlordiazepoxide will display one or more 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

In animal models, the oral LD₅₀ of chlordiazepoxide is 537 mg/kg. Somnolence (or drowsiness) is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods. ... In physiology and medicine, hypotension refers to an abnormally low blood pressure. ... In medicine, hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (hypo means below) to perform needed gas exchange. ... Many different terms are often used to describe what is collectively known as dizziness. ... For other uses, see Coma (disambiguation). ...

Chlordiazepoxide is a drug which is very frequently involved in drug intoxication, including overdose.^[21] Chlordiazepoxide overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. The antidote for an overdose of chlordiazepoxide (or any other benzodiazepine) is flumazenil (Anexate®). An antidote is a substance which can counteract a form of poisoning. ... Flumazenil (flumazepil, Anexate®, Lanexat®, Mazicon®, Romazicon®) is a benzodiazepine antagonist, used as an antidote in the treatment of benzodiazepine overdose. ...

Legal status

Internationally, chlordiazepoxide is a Schedule IV drug under the Convention on Psychotropic Substances[1]. Convention on Psychotropic Substances Opened for signature February 21, 1971 in Vienna Entered into force August 16, 1976 Conditions for entry into force 40 ratifications Parties 175 The Convention on Psychotropic Substances is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, and psychedelics. ...

Toxicity

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.^[22] Nitrazepam (marketed under the trade names Mogadon®, Nitredon®, Nilandron®) is a powerful hypnotic drug, which is a benzodiazepine derivative. ... Diazepam (IPA: ), first marketed as Valium by Hoffmann-La Roche) is a benzodiazepine derivative drug. ... Schematic diagram of a sperm cell, showing the (1) acrosome, (2) cell membrane, (3) nucleus, (4) mitochondria, and (5) flagellum (tail) A sperm cell, or spermatozoon ( spermatozoa) (in Greek: sperm = semen and zoon = alive), is the haploid cell that is the male gamete. ...

Trade names

• Alpoxid
• Klopoxid
• Librium
• Librocol
• Librelease
• Libritabs
• Limbitrol
• Menrium
• Novo-Poxide
• Poxidium
• Risolid
• Defobin
• Elenium

Combination Drugs

• Librax - chlordiazepoxide and clidinium

Clidinium (as clidinium bromide) is an anticholinergic medication. ...

External links

• Rx-List.com - Chlordiazepoxide
• Inchem.org - Chlordiazepoxide

References