Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

17. Pain and Addiction 381codeine, oxycodone, or propoxyphene). If the maximum daily dose of thenonopioid analgesic is reached without providing adequate pain relief, thepatient is considered for a trial of a single entity pure agonist drug. Tramadol isa centrally acting analgesic with a mechanism that is partially opioid and also iscommonly tried for moderate pain.Pure agonist drugs commonly employed for severe pain include morphine,hydromorphone, oxycodone, fentanyl (transdermal formulation), levorphanol,oxymorphone (rectal formulation and oral formulation in development), andmethadone. Some clinicians use meperidine in this setting, but this generallyshould be avoided because of potential toxicity (dysphoria, tremulousness,hyperreflexia, and seizures) related to the accumulation of a metabolite(normeperidine), especially in renally impaired patients (Kaiko et al., 1983).The modified-release, long-acting drugs now are usually favored for thetreatment of chronic pain. These include several morphine formulations, transdermalfentanyl, and an oxycodone formulation. Other modified release drugs,such as oxymorphone, hydromorphone, and buprenorphine, will most likely beavailable soon. Methadone is long acting by virtue of its half-life; it, too, isoften considered in this setting (see below).There is great individual variation in the response to the different pureagonist drugs, an observation that has justified the use of sequential opioid trialsto identify the most favorable drug. This practice is generally known as opioid“rotation” (de Stoutz, Bruera, & Suarez-Almazor, 1995). Initial drug selection isusually influenced by prior experience with opioids, cost, and the preferences ofthe patient. Morphine has active metabolites that accumulate in patients withrenal insufficiency (Peterson, Randall, & Paterson, 1990; Sjogren, 1997) andmay be less preferred when renal function is expected to vary. On the basis ofextensive clinical observation, transdermal fentanyl may be preferred whenopioids are expected to cause severe constipation or other gastrointestinal toxicities.Despite the media awareness of oxycodone abuse, there is no substantiveevidence that this drug possesses characteristics that increase its risk relative toothers. Nonetheless, if street value is an issue that influences drug selection,drugs that raise concern now include oxycodone, hydrocodone, and hydromorphone.Methadone is gaining in popularity as a drug for long-term opioid therapyfor pain. It is relatively inexpensive, has no active metabolites, and may possesshigh potency when substituted for another pure mu agonist drug. The lattereffect may be related to the d-isomer of the commercially available racemicmixture, which is an antagonist at the N-methyl-D-aspartate (NMDA) receptor(Bruera & Neumann, 1999). Studies of NMDA antagonists suggest that thiseffect may be associated with an independent analgesic potential, and the abilityto partially reverse opioid tolerance (Davis & Inturrisi, 1999).Enthusiasm for the expanded use of methadone as an analgesic is temperedby several characteristics. Despite its long half-life, and contrary to its daily