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Chapter 30: Chronic Opioid Dependence and Therapy

Sandy Christiansen; Brian S. Freeman

INTRODUCTION

Over the last decade, chronic opioid use has garnered support for the treatment of terminal cancer pain. It also has been prescribed for noncancer pain. However, chronic opioid therapy (COT) is not without risk, or as one might expect, without controversy. Numerous potential ramifications exist, including maintaining nontoxic therapeutic levels that enhance livelihood, minimizing adverse effects, avoiding illicit diversion and abuse, and prescribing within the legal boundaries. Should aberrant use become a problem or if treatment endpoints are not met, alternatives to COT need to be sought for pain management.

CHRONIC OPIOID DEPENDENCE

The end goal of COT is to improve the functionality of the patient by allowing better daily control of the chronic pain. There are multiple routes of administration of COT that make this possible, including oral, sublingual, buccal, intranasal, transdermal, intramuscular, intrathecal, and, rarely, intravenous. The route selected should best suit the patient’s comorbidities. For example, a patient with oral cancer would likely be a better candidate for the transdermal rather than oral route. There are a multitude of therapeutic options for chronic opioid therapy (Table 30-1).

TABLE 30-1Therapeutic Options for Chronic Opioid Therapy
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TABLE 30-1 Therapeutic Options for Chronic Opioid Therapy
Opioid Analgesic Duration (h) Key Points
Morphine Short-acting (4–5)

Hydrophilic. Good option when serotonin syndrome is a concern. Patients receiving chronic morphine metabolize morphine to hydromorphone, which may be reflected on the urine toxicology screen

Liver produces morphine metabolites, M3G and M6G, which are excreted by the kidneys and can accumulate to toxic doses with renal impairment
Codeine Short-acting (2–4) Patients with genetic polymorphisms in CYP2D6 have decreased or absent analgesic response, as this enzyme is necessary for conversion to its active form of morphine
Oxycodone Short-acting

Also requires CYP2D6 for metabolism to an active compound, oxymorphone.

Caution must be exercised when given concomitantly with serotonergic drugs as can precipitate serotonin syndrome
Hydromorphone Short-acting (3–4) Hydrophilic. Metabolized in liver to H3G, which can potentiate neurotoxicity effects when accumulates due to renal impairment
Fentanyl patch Long-acting Lipophilic. Beneficial for patients with GI issues. Reaches steady state in 6 days
Methadone Long-acting Good option for patients with short gut syndrome as well as ESRD with or without dialysis. Caution must be exercised in patients with ESLD or prolonged QT

Physicians should consider using COT with the aim of providing safe, steady levels of analgesic and minimizing the peaks and troughs that can be associated with worsening pain or side effects. Common adverse effects of opioids include nausea, constipation, sedation, pruritus, and respiratory depression. Notably, constipation is often resistant to tolerance. Other side effects of opioids include urinary retention, decreased lower esophageal sphincter tone, increased tone at the sphincter of Oddi, decreased gastric motility, and decreased pancreatic and gastric secretions.

While side effects may limit successful COT, another feared adverse ...

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