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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Cardiac effects in patients using SSRI antidepressants - selective serotonin reuptake inhibitor - Tips from Other Journals
From American Family Physician, 8/1/97 by Grace Brooke Huffman

About one fifth of patients who have had myocardial infarctions experience major depression. However, the cardiovascular side effects of some antidepressants have made physicians cautious about prescribing them to depressed patients with heart disease. Sheline and colleagues review the safety of selective serotonin reuptake inhibitors (SSRIs) in terms of cardiovascular side effects.

Antidepressants are known to cause conduction changes, as well as changes in heart rate, contractility and rhythm. Orthostatic hypotension is also a frequent problem. A MEDLINE search revealed that SSRIs may cause atrial fibrillation, atrial flutter and supraventricular tachycardia. In overdose, fluoxetine has been reported to cause sinus tachycardia, junctional rhythms and trigeminy. However, the total incidence of adverse cardiac effects was less than 0.0003 percent.

It seems that the main reason for adverse effects of SSRIs is the large number of drug interactions (see the accompanying table). Certain antihistamines are known to cause life-threatening arrhythmias when taken in conjunction with SSRIs. Other adverse effects include serotonergic syndrome, which can occur when SSRIs are taken in conjunction with monoamine oxidase inhibitors or tryptophan. It must be remembered that the long half-life of some SSRIs can cause interactions even after the SSRI has been discontinued.

The authors conclude that SSRIs are safe and do not have a high rate of cardiovascular adverse events. However, further study is needed to determine whether tricyclic antidepressants and SSRIs are equally efficacious in patients with cardiovascular disease. Overall, the risks of allowing depression to go untreated are probably higher than the risks of cardiovascular side effects associated with the use of antidepressants when proper precautions are taken.

Drug Metabolism Affected by Selective Serotonin Reuptake Inhibition

Antiarrhythmics Encainide Flecainide Lidocaine Mexiletine Propafenone Quinidine

Antihistamines Astemizole Terfenadine

Benzodiazepines Alprazolam Bromazepam Diazepam Midazolam Triazolam

Beta blockers Alprenolol Bufarolol Metoprolol Propranolol Timolol

Calcium channel blockers Diltiazem Felodipine Nifedipine Verapamil

Neuroleptics Clozapine Haloperidol Thioridazine Zuclopenthixol

Opiates Codeine Dextromethorphan Ethylmorphine

SSRIs Citalopram Fluoxetine Fluvoxamine Norfluoxetine Paroxetine Sertraline

Miscellaneous Amiflamine Brofaromine Caffeine Carbamazepine Cortisol Cyclosporin A Dexamethasone Erythromycin Ethinylestradiol 4-Hydro-amphetamine Hexobarbital Indoramin Omeprazole Paracetamol Perhexiline Phenformin Phenytoin Mephobarbital Proguanil Tacrine Tamoxifen Tolbutamide Tomoxetine Vinblastine Warfarin

SSRIs = selective serotonin reuptake inhibitors.

Reprinted with permission from Sheline YI, Freedland KE, Carney RM. How safe are serotonin reuptake inhibitors for depression in patients with coronary heart disease? Am J Med 1997;102:54-9.

Sheline YI, et al. How safe are serotonin reuptake inhibitors for depression in patients with coronary heart disease? Am J Med 1997;102:54-9.

COPYRIGHT 1997 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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