Benzodiazepines: use in pain management and palliative care

Benzodiazepines: use in pain management and palliative care 

Introduction

Benzodiazepines have a limited role in pain management and should only be considered for short-term use. They are not recommended for use in nonmalignant persistent pain.

Flumazenil, a benzodiazepine antagonist, can be used in hospitalised patients to reverse the therapeutic effects of benzodiazepines, including anaesthesia and sedation. Flumazenil should be administered under the guidance of an anaesthetist or experienced physician.

Clonazepam

The principal advantage of clonazepam is its strong anxiolytic and antiepileptic effect, but it also has sedative and muscle relaxant actions. It may be useful in the treatment of myoclonus. It is a long-acting benzodiazepine with no active metabolites.

The drop formulation makes clonazepam easy to administer orally, but care must be taken to ensure the mouth is moist. The parenteral preparation has been used subcutaneously

Diazepam

Diazepam has strong anxiolytic, muscle relaxant and antiepileptic effects, and moderate sedative effects. Diazepam has a long half-life, and its active metabolites with even longer half-lives accumulate in the body over time.

Diazepam is not suitable for intramuscular use because of poor and erratic absorption, but it is absorbed well orally and rectally. To administer rectally, use the oral or injectable solution in a syringe attached to a short catheter, and introduce alongside a well-lubricated gloved finger that has been inserted into the rectum. [Note 1]

Midazolam

Midazolam, a water-soluble benzodiazepine, is indicated for minor procedures, seizures, or as a sedative in an emergency when sedation is acceptable to aid symptom relief (eg asphyxia, exsanguination, severe restlessness). It has a rapid onset of action—2 to 3 minutes if given intravenously or 5 to 10 minutes if given subcutaneously—and a relatively short duration of action—15 minutes to several hours. Midazolam can also be administered by the buccal and intranasal routes. It has a plasma half-life of 2 to 5 hours.

Care needs to be exercised if midazolam is given intravenously because it may cause transient apnoea and hypotension. One active metabolite relies on renal excretion and can accumulate in patients with renal impairment. Enhanced effects may result from drug interactions with diltiazem, erythromycin, itraconazole, ketoconazole and possibly fluconazole.

Lorazepam

Lorazepam has some antinauseant activity in addition to anxiolytic (eg it is useful in panic attacks) and amnesic properties. It may be used for anticipatory emesis (nausea and vomiting often beginning before the administration of chemotherapy) in patients with poor control of emesis during previous cycles of chemotherapy. Lorazepam is a medium-acting benzodiazepine.

Alprazolam

Alprazolam has been used in the treatment of anxiety and panic disorder. It is a short-acting benzodiazepine with a rapid onset of action.

Note 1: There is no rectal formulation of diazepam marketed in Australia. A formulation for rectal use is prepared in some hospital pharmacies and provided under specialist advice to parents and carers who have been trained in its use. See, for example, the Melbourne Royal Children's Hospital website.