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ANESTHETIC PHARMACOLOGY

Are Peripheral Opioid Antagonists the Solution to Opioid Side Effects?

John J. Bates, MRCPI, FCARCSI^*, Joseph F. Foss, MD, and Damian B. Murphy, MD, FFARCSI^*

*Department of Anaesthesia and Intensive Care Medicine, Cork University Hospital, Ireland; and Clinical Research, Adolor Inc, Exton, Pennsylvania

Address correspondence and reprint requests to John J. Bates, Department of Intensive Care Medicine, Alfred Hospital, Commercial Rd, Prahran, Victoria 3181, Australia. Address e-mail to jbates{at}esatclear.ie

Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role.

IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

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