Thursday, October 8, 2009

Medication Pearls For Practice: Methadone And Sleep Apnea

"Medication Pearls For Practice" is a new column to be a regular feature here at Onco-PRN. With my role in the Pain and Paliative Care Clinic, expect a lot of pain and symtom control related medication topics. Of course, oncology medications will also be featured.

In this post, key points taken from the Pharmacist's Letter are in bold and italicized.

From: Canadian Pharmacist's Letter 2008; 15(10):241007

Medications that Can Exacerbate Sleep Apnea

“A number of medications, especially CNS depressants such as opioids, benzodiazepines, and muscle relaxants can potentially exacerbate sleep apnea.

*Recently, central sleep apnea has been reported with chronic opioid use and up to 30% of stable methadone maintenance treatment patients have central sleep apnea. In one study (n=50), patients on methadone maintenance therapy were found to have significantly less rapid eye movement (REM) sleep. Central sleep apnea occurred more often in non-REM sleep in methadone maintenance therapy patients. In contrast, respiratory disturbances occur more often during REM sleep with obstructive apnea. These patients had normal resting cardiac function.

*In another study (n=140), the association of methadone, non-methadone opioids, and benzodiazepines with sleep apnea was examined. In the study, patients taking methadone and benzodiazepines concomitantly were found to have a significantly higher rate of central sleep apnea. In the 33% of patients taking methadone, the median daily dosage of morphine equivalents was 187.5 mg/day. The median daily dosage of sustained-release opioids other than methadone in morphine equivalents was 187.5 mg/day. In 36% of patients taking benzodiazepines, the median daily dosage in diazepam equivalents was 15 mg/day. Results of the study showed that 75% of the patients had apnea/hypopnea episodes during sleep. Thirty-nine percent had obstructive sleep apnea, 4% had sleep apnea of an indeterminate type, 24% had central sleep apnea, and 8% had both central and obstructive sleep apnea. Increased dosage of methadone was associated with a higher incidence of central sleep apnea. In contrast, equivalent doses of non-methadone opioids were not found to be associated with increased risk for sleep apnea. The combination of methadone and benzodiazepine also caused significantly more sleep apnea. There are data suggesting that benzodiazepines could possibly inhibit methadone metabolism, prolonging its effect; therefore, this combination should be used cautiously.

In both of these studies presentation of central sleep apnea was atypical compared to those with chronic heart failure (no Cheyne-Stokes respiration, no crescendo-decrescendo pattern of tidal volume).

The cause of central sleep apnea associated with chronic opioid use is likely multifactorial, involving the change of sleep architecture (REM, non-REM, sleep stages, etc) and respiratory depression effect.

Patients with sleep apnea are more likely to experience exacerbation of symptoms when treated with opioids. It is especially important to use caution when titrating opioid analgesic doses in this patient population. The use of patient controlled analgesia (PCA) should be monitored closely in this patient population.”

Feel free to comment below and if you would like to contribute to this featured column topic, "Medication Pearls For Practice", email me at:


Snoring October 11, 2009 at 11:52 PM  

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Treatment for Sleep Apnea

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Welcome and thanks for visiting Onco-P.R.N. - The oncology website with a focus on all things oncology pharmacy/pain/palliative care-related. It is intended to be an information resource for those pharmacist and relevant health care professionals involved in whatever fashion with cancer and palliative care. Stay tuned for the latest and greatest links and information with respect to: oncology medications, continuing education, pharmaceutical care initiatives, pain and symptom control, supportive care topics, and whatever else that might fit into the theme.

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Pharmacy History

"The earliest known compilation of medicinal substances was ARIANA the Sushruta Samhita, an Indian Ayurvedic treatise attributed to Sushruta in the 6th century BC. However, the earliest text as preserved dates to the 3rd or 4th century AD.
Many Sumerian (late 6th millennium BC - early 2nd millennium BC) cuneiform clay tablets record prescriptions for medicine.[3]

Ancient Egyptian pharmacological knowledge was recorded in various papyri such as the Ebers Papyrus of 1550 BC, and the Edwin Smith Papyrus of the 16th century BC.

The earliest known Chinese manual on materia medica is the Shennong Bencao Jing (The Divine Farmer's Herb-Root Classic), dating back to the 1st century AD. It was compiled during the Han dynasty and was attributed to the mythical Shennong. Earlier literature included lists of prescriptions for specific ailments, exemplified by a manuscript "Recipes for 52 Ailments", found in the Mawangdui tomb, sealed in 168 BC. Further details on Chinese pharmacy can be found in the Pharmacy in China article."

From Wikipedia:

Journal of Palliative Medicine - Table of Contents

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