People (Births)
- 1888 – Ernst Kretschmer, German psychiatrist and author (d. 1964).
Ernst Kretschmer
Ernst Kretschmer (08 October 1888 to 08 February 1964) was a German psychiatrist who researched the human constitution and established a typology.
Posts
What is Clorazepate?
Introduction
Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiazepine and serves as a majoritive prodrug for the equally long-lasting desmethyldiazepam, which is rapidly produced as an active metabolite. Desmethyldiazepam is responsible for most of the therapeutic effects of clorazepate.
It was patented in 1965 and approved for medical use in 1967.
Medical Uses
Clorazepate is used in the treatment of anxiety disorders and insomnia. It may also be prescribed as an anticonvulsant or muscle relaxant. It is also used as a premedication.
Clorazepate is prescribed principally in the treatment of alcohol withdrawal and epilepsy, although it is also a useful anxiolytic because of its long half-life. The normal starting dosage range of Clorazepate is 15 to 60 mg per day. The drug is to be taken two to four times per day. Dosages as high as 90 to 120 mg per day may be used in the treatment of acute alcohol withdrawal. In the United States and Canada, Clorazepate is available in 3.75, 7.5, and 15 mg capsules or tablets. In Europe, tablet formations are 5 mg, 10 mg, 20 mg and 50 mg. Clorazepate SD (controlled release) is available and may have a reduced incidence of adverse effects. The sustained-release formulation of clorazepate has some advantages in that, if a dose is missed, less profound fluctuations in blood plasma levels occur, which may be helpful to some people with epilepsy at risk of break-through seizures.
Adverse Effects
Adverse effects of clorazepate include tolerance, dependence, withdrawal reactions, cognitive impairment, confusion, anterograde amnesia, falls in the elderly, ataxia, hangover effects, and drowsiness. It is unclear whether cognitive deficits resulting from the long-term use of benzodiazepines return to normal or persist indefinitely after withdrawal from benzodiazepines. Benzodiazepines are also known to cause or worsen depression. Paradoxical effects including excitement and paradoxical worsening of seizures can sometimes result from the use of benzodiazepines. Children, the elderly, individuals with a history of alcohol use disorder or a history of aggressive behaviour and anger are at greater risk of developing paradoxical reactions to benzodiazepines.
In September 2020, the US Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of non-medical use, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.
Tolerance, Dependence and Withdrawal
Refer to Benzodiazepine Withdrawal Syndrome.
Delirium has been noted from discontinuation from clorazepate. A benzodiazepine dependence occurs in approximately one third of patients who take benzodiazepines for longer than 4 weeks, which is characterised by a withdrawal syndrome upon dose reduction. When used for seizure control, tolerance may manifest itself with an increased rate of seizures as well an increased risk of withdrawal seizures. In humans, tolerance to the anticonvulsant effects of clorazepate occurs frequently with regular use. Due to the development of tolerance, benzodiazepines are, in general, not considered appropriate for the long-term management of epilepsy; increasing the dose may result only in the developing of tolerance to the higher dose combined with worsened adverse effects. Cross-tolerance occurs between benzodiazepines, meaning that, if individuals are tolerant to one benzodiazepine, they will display a tolerance to equivalent doses of other benzodiazepines. Withdrawal symptoms from benzodiazepines include a worsening of pre-existing symptoms as well as the appearance of new symptoms that were not pre-existing. The withdrawal symptoms may range from mild anxiety and insomnia to severe withdrawal symptoms such as seizures and psychosis. Withdrawal symptoms can be difficult in some cases to differentiate between pre-existing symptoms and withdrawal symptoms. Use of high doses, long-term use and abrupt or over-rapid withdrawal increases increase the severity of withdrawal syndrome. However, tolerance to the active metabolite of clorazepate may occur more slowly than with other benzodiazepines. Regular use of benzodiazepines causes 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 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 diarrhoea.
Interactions
All sedatives or hypnotics e.g. other benzodiazepines, barbiturates, antiepileptic drugs, alcohol, antihistamines, opioids, neuroleptics, sleep aids are likely to magnify the effects of clorazepate on the central nervous system. Drugs that may interact with clorazepate include, digoxin, disulfiram, fluoxetine, isoniazid, ketoconazole, levodopa, metoprolol, hormonal contraceptives, probenecid, propranolol, rifampin, theophylline, valproic acid. Selective serotonin reuptake inhibitors (SSRI), cimetidine, macrolide antibiotics and antimycotics inhibit the metabolism of benzodiazepines and may result in increased plasma levels with resultant enhancement of adverse effects. Phenytoin, phenobarbital, and carbamazepine have the opposite effect, with coadministration leading to increased metabolism and decreased therapeutic effects of clorazepate.
Contraindications and Special Caution
Benzodiazepines require special precaution if used in the elderly, children, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.
Clorazepate if used late in pregnancy, the third trimester, causes a definite risk of severe benzodiazepine withdrawal syndrome in the neonate with symptoms including hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Floppy infant syndrome and sedation in the newborn may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.
Special precaution is required when using clorazepate in the elderly because the elderly metabolise clorazepate more slowly, which may result in excessive drug accumulation. Additionally the elderly are more sensitive to the adverse effects of benzodiazepines compared to younger individuals even when blood plasma levels are the same. Use of benzodiazepines in the elderly is only recommended for 2 weeks and it is also recommended that half of the usual daily dose is prescribed.
Pharmacology
Clorazepate is a “classical” benzodiazepine. Other classical benzodiazepines include chlordiazepoxide, diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, bromazepam and flurazepam. Clorazepate is a long-acting benzodiazepine drug. Clorazepate produces the active metabolite desmethyl-diazepam, which is a partial agonist of the GABAA receptor and has a half life of 20-179 hours; a small amount of desmethyldiazepam is further metabolised into oxazepam. Clorazepate exerts its pharmacological properties via increasing the opening frequency of the chloride ion channel of GABAA receptors. This effect of benzodiazepines requires the presence of the neurotransmitter GABA and results in enhanced inhibitory effects of the neurotransmitter GABA acting on GABAA receptors. Clorazepate, like other benzodiazepines, is widely distributed and is highly bound to plasma proteins; clorazepate also crosses readily over the placenta and into breast milk. Peak plasma levels of the active metabolite desmethyl-diazepam are seen between 30 minutes and 2 hours after oral administration of clorazepate. Clorazepate is completely metabolised to desmethyl-diazepam in the gastrointestinal tract and thus the pharmacological properties of clorazepate are largely due to desmethyldiazepam.
Chemistry
Clorazepate is used in the form of a dipotassium salt. It is unusual among benzodiazepines in that it is freely soluble in water.
Clorazepate can be synthesized starting from 2-amino-5-chlorobenzonitrile, which upon reaction with phenylmagnesium bromide is transformed into 2-amino-5-chlorbenzophenone imine. Reacting this with aminomalonic ester gives a heterocyclisation product, 7-chloro-1,3-dihydro-3-carbethoxy-5-phenyl-2H-benzodiazepin-2-one. Upon hydrolysis using an alcoholic solution of potassium hydroxide forms a dipotassium salt, chlorazepate.
Legal Status
In the United States, clorazepate is listed under Schedule IV of the Controlled Substances Act.
This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Clorazepate >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.
On This Day … 07 October [2022]
People (Births)
- 1927 – R.D. Laing, Scottish psychiatrist and author (d. 1989).
People (Deaths)
- 1926 – Emil Kraepelin, German psychologist and academic (b. 1856).
R.D. Laing
Ronald David Laing (07 October 1927 to 23 August 1989), usually cited as R.D. Laing, was a Scottish psychiatrist who wrote extensively on mental illness – in particular, the experience of psychosis. Laing’s views on the causes and treatment of psychopathological phenomena were influenced by his study of existential philosophy and ran counter to the chemical and electroshock methods that had become psychiatric orthodoxy. Taking the expressed feelings of the individual patient or client as valid descriptions of personal experience rather than simply as symptoms of mental illness, Laing regarded schizophrenia as a theory not a fact. Though associated in the public mind with the anti-psychiatry movement, he rejected the label. Politically, he was regarded as a thinker of the New Left. Laing was portrayed by David Tennant in the 2017 film Mad to Be Normal.
Emil Kraepelin
Emil Wilhelm Georg Magnus Kraepelin (15 February 1856 to 07 October 1926) was a German psychiatrist.
H.J. Eysenck’s Encyclopaedia of Psychology identifies him as the founder of modern scientific psychiatry, psychopharmacology and psychiatric genetics.
Kraepelin believed the chief origin of psychiatric disease to be biological and genetic malfunction. His theories dominated psychiatry at the start of the 20th century and, despite the later psychodynamic influence of Sigmund Freud and his disciples, enjoyed a revival at century’s end. While he proclaimed his own high clinical standards of gathering information “by means of expert analysis of individual cases”, he also drew on reported observations of officials not trained in psychiatry.
His textbooks do not contain detailed case histories of individuals but mosaic-like compilations of typical statements and behaviours from patients with a specific diagnosis. He has been described as “a scientific manager” and “a political operator”, who developed “a large-scale, clinically oriented, epidemiological research programme”.
On This Day … 06 October [2022]
People (Births)
- 1915 – Carolyn Goodman, American psychologist and activist (d. 2007).
- 1934 – Marshall Rosenberg, American psychologist and author (d. 2015).
Carolyn Goodman
Carolyn Elizabeth Goodman (née Drucker; 06 October 1915 to 17 August 2007) was an American clinical psychologist who became a prominent civil rights advocate after her son, Andrew Goodman and two other civil rights workers, James Chaney and Michael Schwerner, were murdered by the Ku Klux Klan in Neshoba County, Mississippi, in 1964.
Politically active until age 90, Goodman came to wide public attention again in 2005. Traveling to Philadelphia, Mississippi, she testified at the murder trial of Edgar Ray Killen, a former Klan leader recently indicted in the case. On 21 June 2005, the 41st anniversary of the killings, a jury acquitted Killen of murder but found him guilty of manslaughter in the deaths of Goodman, Chaney, and Schwerner.
Marshall Rosenberg
Marshall Bertram Rosenberg (06 October 1934 to 07 February 2015) was an American psychologist, mediator, author and teacher. Starting in the early 1960s, he developed nonviolent communication, a process for supporting partnership and resolving conflict within people, in relationships, and in society. He worked worldwide as a peacemaker and in 1984, founded the Centre for Nonviolent Communication, an international non-profit organisation for which he served as Director of Educational Services.
According to his biographer, Marjorie C. Witty, “He has a fierce face – even when he smiles and laughs. The overall impression I received was of intellectual and emotional intensity. He possesses a charismatic presence.”
On This Day … 04 October [2022]
People (Births)
- 1929 – John E. Mack, American psychiatrist and author (d. 2004).
John E. Mack
John Edward Mack (04 October 1929 to 27 September 2004) was an American psychiatrist, writer, and professor and the head of the department of psychiatry at Harvard Medical School. In 1977, Mack won the Pulitzer Prize for his book A Prince of Our Disorder on T.E. Lawrence.
As the head of psychiatry at Harvard Medical School, Mack’s clinical expertise was in child psychology, adolescent psychology, and the psychology of religion. He was also known as a leading researcher on the psychology of teenage suicide and drug addiction, and he later became a researcher in the psychology of alien abduction experiences.
On This Day … 03 October [2022]
People (Deaths)
- 2014 – Benedict Groeschel, American priest, psychologist, and talk show host (b. 1933).
Benedict Groeschel
Benedict Joseph Groeschel, C.F.R. (23 July 1933 to 03 October 2014) was an American Franciscan friar, Catholic priest, retreat master, author, psychologist, activist, and television host. He hosted the television talk program Sunday Night Prime (originally Sunday Night Live) broadcast on the Eternal Word Television Network, as well as several serial religious specials.
He founded the Office for Spiritual Development for the Roman Catholic Archdiocese of New York. He was Associate Director of the Trinity Retreat House for clergy and executive director of St. Francis House. He was professor of pastoral psychology at St. Joseph’s Seminary in New York and an adjunct professor at the Institute for Psychological Sciences in Arlington, Virginia. He was one of the founders of the Franciscan Friars of the Renewal and among his close friends were Mother Teresa, Mother Angelica and Alice von Hildebrand.
On This Day … 02 October [2022]
People (Deaths)
- 2012 – J. Philippe Rushton, English-Canadian psychologist, theorist, academic (b. 1943).
J. Philippe Rushton
John Philippe Rushton (03 December 1943 to 02 October 2012) was a Canadian psychologist and author. He taught at the University of Western Ontario until the early 1990s, and became known to the general public during the 1980s and 1990s for research on race and intelligence, race and crime, and other purported racial correlations.
Rushton’s work has been heavily criticized by the scientific community for the questionable quality of its research, with many academics arguing that it was conducted under a racist agenda. From 2002 until his death, he served as the head of the Pioneer Fund, an organization founded in 1937 to promote eugenics, which has been described as racist and white supremacist in nature, and as a hate group by the Southern Poverty Law Centre. He also published articles in and spoke at conferences organized by the white supremacist magazine American Renaissance.
Rushton was a Fellow of the Canadian Psychological Association and a onetime Fellow of the John Simon Guggenheim Memorial Foundation. In 2020, the Department of Psychology of the University of Western Ontario released a statement stating that “much of [Rushton’s] research was racist”, was “deeply flawed from a scientific standpoint”, and “Rushton’s legacy shows that the impact of flawed science lingers on, even after qualified scholars have condemned its scientific integrity.” As of 2021, Rushton has had six research publications retracted.
On This Day … 01 October [2022]
People (Births)
- 1915 – Jerome Bruner, American psychologist and author (d. 2016).
Jerome Bruner
Jerome Seymour Bruner (01 October 1915 to 05 June 2016) was an American psychologist who made significant contributions to human cognitive psychology and cognitive learning theory in educational psychology. Bruner was a senior research fellow at the New York University School of Law. He received a B.A. in 1937 from Duke University and a Ph.D. from Harvard University in 1941. He taught and did research at Harvard University, the University of Oxford, and New York University. A Review of General Psychology survey, published in 2002, ranked Bruner as the 28th most cited psychologist of the 20th century.
On This Day … 30 September [2022]
People (Births)
- 1897 – Charlotte Wolff, German-English physician and psychotherapist (d. 1986).
- 1911 – Gustave Gilbert, American psychologist (d. 1977).
Charlotte Wolff
Charlotte Wolff (30 September 1897 to 12 September 1986) was a German-British physician who worked as a psychotherapist and wrote on sexology and hand analysis. Her writings on lesbianism and bisexuality were influential early works in the field.
Gustave Gilbert
Gustave Mark Gilbert (30 September 1911 to 06 February 1977) was an American psychologist best known for his writings containing observations of high-ranking Nazi leaders during the Nuremberg trials. His 1950 book The Psychology of Dictatorship was an attempt to profile the Nazi German dictator Adolf Hitler using as reference the testimonials of Hitler’s closest generals and commanders. Gilbert’s published work is still a subject of study in many universities and colleges, especially in the field of psychology.
On This Day … 29 September [2022]
People (Deaths)
- 2007 – Yıldırım Aktuna, Turkish psychiatrist and politician, Turkish Minister of Health (b. 1930).
Yildirim Aktuna
Yıldırım Aktuna (1930 to 29 September 2007) was a Turkish psychiatrist, politician, district mayor and government minister in a number of cabinets.
Early Years
He was born 1930 in Istanbul. After completing the high school in Karşıyaka, Izmir in 1948, Yıldırım Aktuna attended the School of Medicine of the University of Istanbul as a cadet. In 1954, he graduated with Doctor of Medicine degree in the rank of a lieutenant.
Military Career
His first post was chief physician officer of the 26th Brigade at the 66th Army Division. After completing a one-year English language course at the Army Language School in Ankara, Aktuna was sent to the United States, where he attended advanced education in general medicine at the Brooke Army Medical Centre in Fort Sam Houston, San Antonio between 1958-1959.
Having returned home, Aktuna specialised in neuropsychiatry at the Gülhane Military Medical Academy in Ankara, finishing in 1962. He then served in the army as medical officer at various places in Turkey. Between 1967-1989, he was lecturer at the Kabul Military Hospital in Afghanistan. In 1970, he retired from the Turkish Army in the rank of a lieutenant colonel.
Civil Service
Switched over to civil service, he firstly was appointed Assistant Chief Physician at the Psychology Clinic of Şişli Children’s Hospital in Istanbul. He later became the chief of that clinic.
Between 1972-1973, Aktuna sojourned in Austria to pursue advanced studies in neurology and electroencephalography (EEG) at the Neurological Clinic of the University of Vienna.
In 1979, Yıldırım Aktuna was appointed Chief Physician of the Bakırköy Psychiatric Hospital in Istanbul, the largest of its art in the country. He modernised the hospital, and devoted himself to raise consciousness for public mental health and to develop contemporary policies on this subject. He established in 1983 an alcohol and drug rehabilitation centre within this hospital, the first facility in Turkey to conduct medical and psychotherapeutic treatment and research for dependency on psychoactive substances as well. For these activities, he was honoured several times by various organisations.
Mental Health Matters 
You must be logged in to post a comment.