|
Course Sample:
Introduction One of the primary goals of pain management is to provide pain relief to optimize quality of life. Morphine, the standard of comparison, is considered to be one of the essential drugs of palliative care and is the most commonly used opioid for relief of moderate to severe cancer pain (Dickerson, 1999; Ripamonti, Groff, Polastri, et al., 1998; Pappagallo & Heinberg, 1997). Morphine and other opioids, such as fentanyl, hydromorphone, and oxycodone are not always effective though, and at some point during their pain management therapy, some patients will need to change medications at least once (Ripamonti, Groff, Polastri, et al., 1998). Response to any opioid is extremely variable. Poor pain relief and unmanageable toxicities are the primary reasons for opioid failure. Other alternatives must be found for patients when opioid failure occurs (Mathew & Storey, 1999). Methadone is often effective in providing good pain relief with few or no adverse side effects, especially for patients where side effects are problematic or with pain that is no longer responsive to other opioids, such as morphine, hydromorphone, and fentanyl. Methadone is typically considered a second line drug for opioid therapy because it is difficult to titrate and dose accurately. As it is best known for maintenance therapy of opioid addictions, many health care providers are confused regarding the legality of prescribing it for pain. Still, because of its characteristics, methadone has indisputable value in pain management and is gaining recognition for use in treatment of chronic, cancer, and palliative pain. Physiology Opioids work by mimicking the actions of endorphins (endogenous opioid compounds) at thethree major opioid receptors sites, Mu (m), Delta (d), and Kappa (k). These receptors are responsible for mediating the various effects of opioids. When an opioid agonist binds to any of these receptor sites, it produces analgesia (Fink & Gates, 1999). An opioid's affinity to bind to one or more of these receptors accounts for its potency and effectiveness in providing pain relief. Most opioids are primarily Mu agonists, blocking the release of transmitters and neuron activation in pain pathways (Wheeler & Dickerson, 2000; Dickerson, 1999; Fink & Gates, 1999). Methadone, like other opioids, has a high affinity for Mu receptors. It also binds to Delta opioid receptors, which are widely distributed in the central nervous system, especially in sensory and spinal pathways associated with pain transmission. Methadone acts as an antagonist to N-methyl-D-aspartate (NMDA) receptors. These receptors are activated in neuropathic pain and methadone provides relief by blocking them (Wheeler & Dickerson, 2000). In addition, antagonism of NMDA by methadone reduces the development of opioid tolerance. These multiple non-opioid receptor effects explain the unexpectedly high analgesic potency (Scimeca, Savage, Portenoy, et. al., 2000; Wheeler & Dickerson, 2000; Ripamonti, Groff, Polastri, et al., 1998; Gannon, 1997). Methadone for Drug Addiction Methadone has been associated with treatment for opioid addiction since 1964 (Baumrucker, 2000; Jamison, Kauffman, & Katz, 2000; Gannon, 1997). Methadone has a slow onset of action and does not produce a euphoria or "rush" when taken orally. When used in addiction therapy, it blocks cravings and withdrawal symptoms for up to 36 hours (Scimeca, Savage, Portenoy, et al., 2000). However, methadone's association with addiction therapy has hindered its use as an opioid analgesia. Many perceive methadone as a drug used only for drug addiction therapy and regulations restrict prescribing methadone for "drug addiction therapy" only by Federal Drug Administration (FDA) approved drug treatment programs. However, the guidelines do not apply when using methadone as an opioid analgesia, yet many health care providers are reluctant to prescribe methadone outside of a drug addiction therapy program for fear of an investigation (Baumrucker, 2000; Jamison, Kauffman, & Katz, 2000; Wheeler & Dickerson, 2000; Gannon, 1997). Advantages of Methadone Despite methadone's history with drug addiction therapy, many feel methadone fulfills the criteria of a broad opioid for treatment of pain because of its multiple receptor effects. The need for a useful alternative to morphine and other Mu agonists has increased interest in methadone as an analgesia (Berger & Dickerson, 2001; Gannon, 1997; Ripamonti, Zecca, & Bruera, 1997). Methadone has many advantages, including: - Excellent absorption from all routes of administration (oral, sublingual, rectal, subcutaneous (can cause local irritation), intramuscular, parental, epidural, and intrathecal)
- Availability in liquid form allowing for high oral doses (benefits patients with escalating doses or unable to swallow a large number of pills)
- High analgesic efficacy (effectiveness of a drug)
- Rapid onset of analgesic relief
- High potency (power of drug to produce desired effects)
- A relatively long half-life lengthening dosing intervals
- A low rate of induction of tolerance
- Significantly less expensive
- No active metabolites to accumulate in patients with renal failure or liver failure
- Potential to control pain unresponsive to morphine, hydromorphone, and fentanyl
- Effective for many types of pain, including neuropathic pain. (Gannon, 1997; Ripamonti, Zecca, & Bruera, 1997)
Methadone has a distinct advantage over other opioids because of these characteristics. Its high potency, long half life, and incomplete cross tolerance are some of the reasons patients rotated to methadone achieve better pain control. Often, patients suffering from side effects on very high doses of other opioids find methadone a better option, since the dose of methadone required for maintaining adequate pain control is usually much lower (Dickerson, 1999; Hagen & Wasylenko, 1999). Methadone is particularly recommended over other strong opioids in the management of neuropathic pain because of its noncompetitive antagonistic activity at the NMDA receptors and activity within the pariaqueductatal gray, part of the descending pain pathway for analgesia (Davis & Walsh, 2001; Oneschuk & Bruera, 2000; Dickerson, 1999; Makin, O'Donnell, Skinner, et al., 1998). Disadvantages of Methadone |
