Bromazepam chemical structure
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Bromazepam

Bromazepam (marketed under brand names Compendium®, Creosedin®, Durazanil®, Lectopam®, Lexaurin®, Lexomil®, Lexotan®, Lexotanil®, Normoc®, Somalium®) is a drug which is a benzodiazepine derivative. It has sedative, hypnotic, anxiolytic and skeletal muscle relaxant properties. more...

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Pharmacology

Its molecular structure is composed of a diazepine connected to two benzene rings, one of which has a bromine atom attached to it. It is a 1,4-benzodiazepine, which means that the nitrogens on the seven-sided diazepine ring are in the 1 and 4 positions.

Bromazepam binds to the GABA receptor GABAA, causing a conformational change and increasing inhibitory effects of GABA. Other neurotransmitters are not influenced. It does not possess any antidepressant qualities. Bromazepam shares with other benzodiazepines the risk of abuse, misuse, psychological and/or physical dependence. According to many psychiatric experts Bromazepam has a greater abuse potential than other benzodiazepines because of fast resorption and rapid onset of action. Due to its relatively short halflife and duration of action (8 to 12 hours), withdrawal symptoms may be more severe and more frequently encountered than with long acting benzodiazepines.

Bromazepam is reported to be metabolized by a hepatic enzyme belonging to the Cytochrome P450 family of enzymes. In 2003, a team led by Dr. Oda Manami at Oita Medical University reported that CYP3A4 was not the responsible enzyme, seeing as itraconazole, a known inhibitor of CYP3A4, did not effect its metabolism. In 1995, J. van Harten at Solvay Duphar B.V.'s Department of Clinical Pharmacology in Weesp reported that fluvoxamine, which is a potent inhibitor of CYP1A2, a less potent CYP3A4 inhibitor, and a negligible inhibitor of CYP2D6, does inhibit its metabolism.

The active metabolite of bromazepam is hydroxybromazepam.

Indications

  • Short-term treatment of insomnia
  • Short-term treatment of anxiety or panic attacks, if a benzodiazepine is required
  • Alleviation of the symptoms of alcohol- and opiate-withdrawal, under close clinical supervision

Availability

Bromazepam is available as a generic in Canada, Germany, Italy, France, Portugal, Switzerland, It is also available in the United Arab Emirates, Venezuela and Columbia in the form of Lexotanil and in Brazil and Portugal in the form of Lexotan.

Dosage

Usually, 3mg to 6mg at bedtime, with additional 1.5mg to 3mg during the next day if needed. Malnourished patients, patients with compromised cardiovascular, liver or renal function, and elderly patients should receive lower doses. In hospitalized patients with severe agitation and/or anxiety, daily doses of up to 24mg have been given and tolerated for a limited period of time. A 3mg dose of bromazepam is equivalent to a 5mg dose of diazepam.

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Benzodiazepines, automobile accidents and the elderly - Tips from Other Journals
From American Family Physician, 1/15/98 by Grace Brooke Huffman

Benzodiazepines are among the most frequently prescribed classes of medications in elderly patients, primarily for treatment of anxiety and insomnia. The many adverse side effects of benzodiazepines, including drowsiness, sedation, confusion and impaired motor function, may have a serious effect on a patient's ability to operate a motor vehicle. Hemmelgarn and colleagues reviewed the association between the type of benzodiazepine used (long- or short-acting) and the risk of injury in a motor vehicle accident.

Individuals were included in the study if they had been driving when an accident occurred that injured at least one person. All study subjects lived in Quebec and were between the ages of 67 and 84 years. Prescription use of a benzodiazepine was confirmed by a review of Quebec province health care service records. Benzodiazepines were classified as having a long half-life (clonazepam, diazepam, clorazepate, chlordiazepoxide, flurazeparn or nitrazepam) or a short half-life (alprazolam, bromazepam, lorazepam, oxazepam, temazepam or triazolam). Study subjects were selected from a cohort of those who met the criteria, and 10 control subjects were randomly selected for each study subject. A total of 5,579 study subjects and 18,490 control subjects were selected for the study.

Regardless of the duration of use, individuals who were currently taking long-acting benzodiazepines had an increased risk of involvement in a motor vehicle accident with injury. However, for those who had just begun taking long-acting benzodiazepines within the last seven days, the risk was even higher (risk ratio: 1.45). The risk dropped to nonsignificant levels if the individual had been taking the drug between eight and 30 days. The risk significantly increased again in study subjects who had used a benzodiazepine for more than 61 days. Those taking short-acting benzodiazepines had no similar risk of involvement in motor vehicle accidents with injury.

The authors conclude that use of long-acting benzodiazepines, particularly within seven days of initiation of treatment, is associated with a significantly high risk of involvement in a motor vehicle accident with injury. Tolerance to the psychomotor effects of long-acting benzodiazepine use does not seem to develop, as had previously been proposed.

Hemmelgarn B, et al. Benzodiazepine use and the risk of motor vehicle crash in the elderly. JAMA 1997,-278.-27-3 1.

COPYRIGHT 1998 American Academy of Family Physicians
COPYRIGHT 2000 Gale Group

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