Clinical Geriatrics

Introduction
The opioid analgesics are among the oldest of drugs in use today, with evidence of use dating back thousands of years. These agents mimic the endogenous opioid peptides and act by reducing neuronal excitability (by hyperpolarizing the neuron via enhancement of potassium ion influx) and inhibiting neurotransmitter release (by reducing calcium ion influx). Their effects are mediated by binding to specific receptors in the central and peripheral nervous systems (Table I).¹

In this two-part article, some general concepts underlying the use of opioid analgesics will be covered, and selected individual agents will be discussed. Part I will provide information on selected general concepts in opioid therapeutics, including the role of opioids in pain management, treatment of concurrent acute pain, toxicity, and drug-drug interactions. Part II, to be published in the next issue of the Journal, will discuss dosing of opioid analgesics, pharmacogenomics, and the individual agents. For the purpose of these articles, the term opioid will refer to all naturally-occurring, semisynthetic and synthetic agents and endogenous peptides that act by binding to one or more opioid receptor types in the body. Only those opioid analgesics available in the United States that are administered orally, transdermally, or transmucosally will be discussed (Table II).¹ Emphasis will be placed on the chronic use of these agents in the older population for the treatment of persistent pain. The following opioid analgesics, which by general consensus should not be used in older individuals, will not be discussed: meperidine; the mixed agonist-antagonists pentazocine, nalbuphine, butorphanol; and the partial agonist buprenorphine. Propoxyphene will similarly not be discussed in light of the actions of a U.S. Food and Drug Administration (FDA) panel that voted 14-12 in early 2009 to recommend withdrawal of all propoxyphene-containing products from the U.S. marketplace. This agent, by general consensus, also should not be used in older individuals.

Selected General Concepts in Opioid Therapeutics

Role of Opioids in Pain Management
Opioid analgesics are an important drug class to consider for the control of moderate-to-severe pain. The paucity of guidelines for opioid use in older persons or discussion of elder-specific issues in general pain guidelines is a reflection of the paucity of studies of these agents in this patient population. However, a review of the evidence base had led to at least some preliminary recommendations for the use of opioids in older patients.²

Few high-quality data exist regarding opioid use in cancer-related pain in older persons. In general, sufficient high-quality data exist in non-elderly cancer populations to consider all opioids to be effective in geriatric cancer pain management, despite the lack of well-designed elder-specific studies.^2,3 The need to maintain continuity of opioid dosing upon transfer across healthcare settings has been identified as a major potential concern in this population, especially if different opioid dose conversion charts and different formulary opioid products are used in the various settings.⁴

In musculoskeletal pain syndromes, a high-quality evidence base demonstrating the efficacy of opioids has been steadily growing. Again, few elder-specific data are available; however, it can be concluded that opioids are effective in these noncancer pain syndromes.^2,3 The major controversy lies in the timing of initiation of opioid analgesia.