Bromazepam Wiki

8/13/2019 Bromazepam Wiki

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Bromazepam(marketed under several brand names,

including Lectopam, Lexotan, Lexilium, Lexaurin, Brazepam, Rekotnil, BromazeandLexotanil)[1]

is

abenzodiazepinederivative drug, patented by Roche in 1963[2]

and developed clinically in the

1970s.[3][4]

It has mainlyanxiolyticproperties and at higher doses of 12 milligrams or more also

showssedative,hypnoticandskeletal muscle relaxantproperties.[5]

Contents

[hide]

1 Indications

2 Side-effects

3 Tolerance, dependence and withdrawal

4 Contraindications and special precautions

o 4.1 Special populations

4.1.1 Elderly

4.1.2 Driving

4.1.3 Pregnancy and breast feeding

5 Interactions

6 Pharmacology

7 Pharmacokinetics

8 Overdose

9 Drug misuse

10 Legal status

11 See also

12 References

13 External links

Indications[edit]

Short-term treatment ofanxietyorpanic attacks,if a benzodiazepine is required.[6]

Premedicationto alleviate anxiety before surgery.[7]

Side-effects[edit]All common side-effects of benzodiazepines have been noted. Consult the article underdiazepam.

Bromazepam 6 mg 3 times daily for 2 weeks taken alone impaired learning capacities significantly in

humans in an experiment. In combination with alcohol the impairments of learning capacity became even

more pronounced.[8]

Impairments to memory functions are common with bromazepam and include a

reducedworking memoryand reduced ability to process environmental information.[9][10][11]

Impaired

memory, visual information processing and sensory data and impaired psychomotor
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performance.[12][13][14]

Deterioration of cognition including attention capacity and impaired co-ordinative

skills.[15][16]

Unsteadiness after taking bromazepam is however less pronounced than other

benzodiazepines such aslorazepam.[17]

Impaired reactive and attention performance, which can impair

driving skills.[18]

Drowsinessand decrease inlibido.[19][20]

On occasion, benzodiazepines can induce extreme alterations in

memory such asanterograde amnesiaandamnesic automatism,which may have medico-legal

consequences. Such reactions occur usually only at the higher dose end of the prescribing spectrum .[21]

Very rarely,dystoniacan develop.[22]

Up to 30% treated on a long-term basis develop a form of dependence, i.e. these patients cannot stop the

medication without experiencing physical and/or psychologicalbenzodiazepine withdrawal symptoms.

Leukopenia and liver-damage of the cholostatic type with or without jaundice (icterus) have additionally

been seen; the original manufacturerRocherecommends regular laboratory examinations to be

performed routinely.

Ambulatory patients should be warned that Bromazepam may impair the ability to drive vehicles and to

operate machinery. The impairment is worsened by consumption of alcohol, because both act as central

nervous system depressants. During the course of therapy, tolerance to the sedative effect usually

develops.

Tolerance, dependence and withdrawal[edit]

Bromazepam shares with other benzodiazepines the risk of abuse, misuse,psychological

dependenceand/orphysical dependence.[23][24]

A withdrawal study demonstrated both psychological

dependence and physical dependence on bromazepam including markedrebound anxietyafter 4 weeks

chronic use. Those whose dose was gradually reduced experienced no withdrawal.[25]

Patients treated with bromazepam for generalised anxiety disorder were found to experience withdrawalsymptoms such as a worsening of anxiety, as well as the development of physical withdrawal symptoms

when abruptly withdrawn from bromazepam.[26]

Abrupt or over rapid withdrawal from bromazepam after

chronic use even at therapeutic prescribed doses can lead to a severe withdrawal syndrome

includingstatus epilepticusand a condition resemblingdelerium tremens.[27][28][29]

Animal studies have shown that chronic administration ofdiazepamor bromazepam causes a decrease

in spontaneous locomotor activity and the turnover of noradrenaline and dopamine and serotonin,

decreased activity of tyrosine hydroxylase and increased levels of the catecholamines. During withdrawal

of bromazepam or diazepam a fall in tryptophan, 5-hydroxytryptamine levels occurs as part of

thebenzodiazepine withdrawal syndrome.[30]

Contraindications and special precautions[edit]

Benzodiazepines require special precaution if used in the elderly, pregnancy, children, alcohol- or drug-

dependent individuals and individuals withcomorbidpsychiatric disorders.[31]

Special populations[edit]

Elderly[edit]
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In 1987, a team of scientists led by Ochs reported that the elimination half-life, peakserum concentration,

andserum free fractionare significantly elevated and theoral clearanceandvolume of

distributionsignificantly lowered in elderly subjects.[32]

The clinical consequence is that the elderly should

be treated with lower doses than younger patients.

Driving[edit]

Bromazepam may affect driving and ability to operate machinery.[33]

Pregnancy and breast feeding[edit]

Bromazepam ispregnancy categoryD, a classification that means that bromazepam has been shown to

cause harm to the unborn child. TheHoffman LaRocheproduct information leaflet warns against breast

feeding while taking bromazepam. There has been at least one report ofsudden infant death

syndromelinked tobreast feedingwhile consuming bromazepam.[34][35]

Interactions[edit]

Cimetidine,fluvoxamineandpropranololcauses a marked increase in thehalf-lifeof bromazepam leading

to increased accumulation of bromazepam.[36][37][38]

Pharmacology[edit]

50 Pills of Lexotanil(containing 6 mg of Bromezepam apiece) as sold byHoffmann-La RocheinGermany

Bromazepam is a "classical" benzodiazepine; other classical benzodiazepines

include;diazepam,clonazepam,oxazepam,lorazepam,nitrazepam,flurazepam,andclorazepate.[39]

Itsmolecular structure is composed of adiazepineconnected to abenzenering and apyridinering, the

benzene ring having abromineatom attached to it.[40]

It is a1,4-benzodiazepine,which means that the

nitrogens on the seven-sided diazepine ring are in the 1 and 4 positions.

Bromazepam binds to theGABAreceptorGABAA,causing a conformational change and increasing

inhibitory effects of GABA. Other neurotransmitters are not influenced. Bromazepam is a long-acting
http://en.wiktionary.org/wiki/serum_concentrationhttp://en.wiktionary.org/wiki/serum_concentrationhttp://en.wiktionary.org/wiki/serum_concentrationhttp://en.wiktionary.org/wiki/serum_free_fractionhttp://en.wiktionary.org/wiki/serum_free_fractionhttp://en.wiktionary.org/wiki/serum_free_fractionhttp://en.wiktionary.org/wiki/oral_clearancehttp://en.wiktionary.org/wiki/oral_clearancehttp://en.wiktionary.org/wiki/oral_clearancehttp://en.wikipedia.org/wiki/Volume_of_distributionhttp://en.wikipedia.org/wiki/Volume_of_distributionhttp://en.wikipedia.org/wiki/Volume_of_distributionhttp://en.wikipedia.org/wiki/Volume_of_distributionhttp://en.wikipedia.org/wiki/Bromazepam#cite_note-bromazepamold-32http://en.wikipedia.org/wiki/Bromazepam#cite_note-bromazepamold-32http://en.wikipedia.org/wiki/Bromazepam#cite_note-bromazepamold-32http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=7http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=7http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=7http://en.wikipedia.org/wiki/Bromazepam#cite_note-33http://en.wikipedia.org/wiki/Bromazepam#cite_note-33http://en.wikipedia.org/wiki/Bromazepam#cite_note-33http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=8http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=8http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=8http://en.wikipedia.org/wiki/Pregnancy_categoryhttp://en.wikipedia.org/wiki/Pregnancy_categoryhttp://en.wikipedia.org/wiki/Pregnancy_categoryhttp://en.wikipedia.org/wiki/Hoffman_LaRochehttp://en.wikipedia.org/wiki/Hoffman_LaRochehttp://en.wikipedia.org/wiki/Hoffman_LaRochehttp://en.wikipedia.org/wiki/Sudden_infant_death_syndromehttp://en.wikipedia.org/wiki/Sudden_infant_death_syndromehttp://en.wikipedia.org/wiki/Sudden_infant_death_syndromehttp://en.wikipedia.org/wiki/Sudden_infant_death_syndromehttp://en.wikipedia.org/wiki/Breast_feedinghttp://en.wikipedia.org/wiki/Breast_feedinghttp://en.wikipedia.org/wiki/Breast_feedinghttp://en.wikipedia.org/wiki/Bromazepam#cite_note-34http://en.wikipedia.org/wiki/Bromazepam#cite_note-34http://en.wikipedia.org/wiki/Bromazepam#cite_note-34http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=9http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=9http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=9http://en.wikipedia.org/wiki/Cimetidinehttp://en.wikipedia.org/wiki/Cimetidinehttp://en.wikipedia.org/wiki/Fluvoxaminehttp://en.wikipedia.org/wiki/Fluvoxaminehttp://en.wikipedia.org/wiki/Fluvoxaminehttp://en.wikipedia.org/wiki/Propranololhttp://en.wikipedia.org/wiki/Propranololhttp://en.wikipedia.org/wiki/Propranololhttp://en.wikipedia.org/wiki/Half-lifehttp://en.wikipedia.org/wiki/Half-lifehttp://en.wikipedia.org/wiki/Half-lifehttp://en.wikipedia.org/wiki/Bromazepam#cite_note-36http://en.wikipedia.org/wiki/Bromazepam#cite_note-36http://en.wikipedia.org/wiki/Bromazepam#cite_note-pmid8846617-38http://en.wikipedia.org/wiki/Bromazepam#cite_note-pmid8846617-38http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=10http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=10http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=10http://en.wikipedia.org/wiki/Hoffmann-La_Rochehttp://en.wikipedia.org/wiki/Hoffmann-La_Rochehttp://en.wikipedia.org/wiki/Hoffmann-La_Rochehttp://en.wikipedia.org/wiki/Germanyhttp://en.wikipedia.org/wiki/Germanyhttp://en.wikipedia.org/wiki/Germanyhttp://en.wikipedia.org/wiki/Diazepamhttp://en.wikipedia.org/wiki/Diazepamhttp://en.wikipedia.org/wiki/Diazepamhttp://en.wikipedia.org/wiki/Clonazepamhttp://en.wikipedia.org/wiki/Clonazepamhttp://en.wikipedia.org/wiki/Clonazepamhttp://en.wikipedia.org/wiki/Oxazepamhttp://en.wikipedia.org/wiki/Oxazepamhttp://en.wikipedia.org/wiki/Oxazepamhttp://en.wikipedia.org/wiki/Lorazepamhttp://en.wikipedia.org/wiki/Lorazepamhttp://en.wikipedia.org/wiki/Lorazepamhttp://en.wikipedia.org/wiki/Nitrazepamhttp://en.wikipedia.org/wiki/Nitrazepamhttp://en.wikipedia.org/wiki/Flurazepamhttp://en.wikipedia.org/wiki/Flurazepamhttp://en.wikipedia.org/wiki/Flurazepamhttp://en.wikipedia.org/wiki/Clorazepatehttp://en.wikipedia.org/wiki/Clorazepatehttp://en.wikipedia.org/wiki/Bromazepam#cite_note-39http://en.wikipedia.org/wiki/Bromazepam#cite_note-39http://en.wikipedia.org/wiki/Bromazepam#cite_note-39http://en.wikipedia.org/wiki/Diazepinehttp://en.wikipedia.org/wiki/Diazepinehttp://en.wikipedia.org/wiki/Diazepinehttp://en.wikipedia.org/wiki/Benzenehttp://en.wikipedia.org/wiki/Benzenehttp://en.wikipedia.org/wiki/Benzenehttp://en.wikipedia.org/wiki/Pyridinehttp://en.wikipedia.org/wiki/Pyridinehttp://en.wikipedia.org/wiki/Pyridinehttp://en.wikipedia.org/wiki/Brominehttp://en.wikipedia.org/wiki/Brominehttp://en.wikipedia.org/wiki/Brominehttp://en.wikipedia.org/wiki/Bromazepam#cite_note-bromazepamstructure-40http://en.wikipedia.org/wiki/Bromazepam#cite_note-bromazepamstructure-40http://en.wikipedia.org/wiki/Bromazepam#cite_note-bromazepamstructure-40http://en.wikipedia.org/wiki/Benzodiazepinehttp://en.wikipedia.org/wiki/Benzodiazepinehttp://en.wikipedia.org/wiki/Benzodiazepinehttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/GABA_A_receptorhttp://en.wikipedia.org/wiki/GABA_A_receptorhttp://en.wikipedia.org/wiki/GABA_A_receptorhttp://en.wikipedia.org/wiki/GABA_A_receptorhttp://en.wikipedia.org/wiki/File:Lexotanil_6_mg.pnghttp://en.wikipedia.org/wiki/File:Lexotanil_6_mg.pnghttp://en.wikipedia.org/wiki/File:Lexotanil_6_mg.pnghttp://en.wikipedia.org/wiki/File:Lexotanil_6_mg.pnghttp://en.wikipedia.org/wiki/GABA_A_receptorhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/Benzodiazepinehttp://en.wikipedia.org/wiki/Bromazepam#cite_note-bromazepamstructure-40http://en.wikipedia.org/wiki/Brominehttp://en.wikipedia.org/wiki/Pyridinehttp://en.wikipedia.org/wiki/Benzenehttp://en.wikipedia.org/wiki/Diazepinehttp://en.wikipedia.org/wiki/Bromazepam#cite_note-39http://en.wikipedia.org/wiki/Clorazepatehttp://en.wikipedia.org/wiki/Flurazepamhttp://en.wikipedia.org/wiki/Nitrazepamhttp://en.wikipedia.org/wiki/Lorazepamhttp://en.wikipedia.org/wiki/Oxazepamhttp://en.wikipedia.org/wiki/Clonazepamhttp://en.wikipedia.org/wiki/Diazepamhttp://en.wikipedia.org/wiki/Germanyhttp://en.wikipedia.org/wiki/Hoffmann-La_Rochehttp://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=10http://en.wikipedia.org/wiki/Bromazepam#cite_note-pmid8846617-38http://en.wikipedia.org/wiki/Bromazepam#cite_note-36http://en.wikipedia.org/wiki/Bromazepam#cite_note-36http://en.wikipedia.org/wiki/Half-lifehttp://en.wikipedia.org/wiki/Propranololhttp://en.wikipedia.org/wiki/Fluvoxaminehttp://en.wikipedia.org/wiki/Cimetidinehttp://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=9http://en.wikipedia.org/wiki/Bromazepam#cite_note-34http://en.wikipedia.org/wiki/Bromazepam#cite_note-34http://en.wikipedia.org/wiki/Breast_feedinghttp://en.wikipedia.org/wiki/Sudden_infant_death_syndromehttp://en.wikipedia.org/wiki/Sudden_infant_death_syndromehttp://en.wikipedia.org/wiki/Hoffman_LaRochehttp://en.wikipedia.org/wiki/Pregnancy_categoryhttp://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=8http://en.wikipedia.org/wiki/Bromazepam#cite_note-33http://en.wikipedia.org/w/index.php?title=Bromazepam&action=edit&section=7http://en.wikipedia.org/wiki/Bromazepam#cite_note-bromazepamold-32http://en.wikipedia.org/wiki/Volume_of_distributionhttp://en.wikipedia.org/wiki/Volume_of_distributionhttp://en.wiktionary.org/wiki/oral_clearancehttp://en.wiktionary.org/wiki/serum_free_fractionhttp://en.wiktionary.org/wiki/serum_concentration


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benzodiazepine and islipophilicand metabolised hepatically via oxidative pathways.[41]

It does not

possess any antidepressant or antipsychotic qualities.[42]

After night time administration of bromazepam a highly significant reduction of gastric acid secretion

occurs during sleep followed by a highly significant rebound in gastric acid production the following day.[43]

Bromazepam alters electrical status of the brain causing an increased beta activity and a decrease inalpha activity in the EEG recordings.

[44]

Pharmacokinetics[edit]

Bromazepam is reported to be metabolized by a hepatic enzyme belonging to the Cytochrome

P450family of enzymes. In 2003, a team led by Dr. Oda Manami at Oita Medical University reported

thatCYP3A4was not the responsible enzyme, seeing asitraconazole,a known inhibitor ofCYP3A4,did

not affect its metabolism.[45]

In 1995, J. van Harten atSolvay Duphar B.V.'s Department of Clinical

Pharmacology inWeespreported thatfluvoxamine,which is a potent inhibitor of CYP1A2, a less

potentCYP3A4inhibitor, and a negligible inhibitor ofCYP2D6,does inhibit its metabolism.[38]

The active metabolite of bromazepam is hydroxybromazepam, which has half-life approximately equal to

that of bromazepam.[citation needed]

Overdose[edit]

Main article:Benzodiazepine overdose

Bromazepam is commonly involved in drug overdoses.[46]

A severe bromazepambenzodiazepine

overdosemay result in an alpha pattern coma type.[47]

The toxicity of bromazepam in overdosage

increases when combined with other CNS depressant drugs such as alcoholor sedative hypnotic

drugs.[48]

Bromazepam is the most common benzodiazepine involved in intentional overdoses

inFrance.[49]

Drug misuse[edit]

See also:Benzodiazepine drug misuse

Bromazepam has a similar misuse risk as other benzodiazepines such as diazepam.[50]

InFrancecar

accidents involving psychotropic drugs in combination found benzodiazepines,

mainlydiazepam,nordiazepam,and bromazepam, to be the most common drug, almost twice that of the

next-most-common drugcannabis.[51]

Bromazepam has also been used for serious criminal offences

including,robberyandhomicideand to carry outsexual assaults.[52][53][54]

Legal status[edit]Bromazepam is aSchedule IVdrug under theConvention on Psychotropic Substances.

[55]

See also[edit]

Benzodiazepine

Benzodiazepine dependence
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