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11 Articles in Volume 13, Issue #6
Ask the Expert: Cash Patient on High-Dose Oxycodone With Negative Urine Screens
Cluster Headache: Providing Relief for a Debilitating Disorder
Editor's Memo: Keeping the Trust in Difficult Times
Gout: New Guidelines for Managing An Ancient Disease
History of Pain: A Brief Overview of the 17th and 18th Centuries
Letters to The Editor: Guidelines for Opioid Prescribing, Drug Legislation
Long-term Opioids, Sickle Cell Disease, and Pain Patches
Lumbar Spinal Stenosis: A Review of the Treatment Options and Modalities
Malabsorption of Opioid Medications
Non-Opioid Pharmaceutical Treatment of Cancer Pain
Treatment of Postherpetic Neuralgia With Low Level Laser Therapy

Non-Opioid Pharmaceutical Treatment of Cancer Pain

Approximately 33% of cancer patients experience long-term pain. Many cancer patients are living longer, shifting pain management from a focus on acute pain to chronic pain. Part 3 of this four-part series on cancer pain will serve as a practical guide for commonly used adjuvant therapies and contain tips for using the most effective agents.
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Adjuvant Analgesics Used For Pain Caused by Bowel Obstruction

Regimens for constipation should be routinely used in most cancer patients on analgesic therapy, particularly if they are sedentary and have poor feedings. Octreotide and anticholinergic medications can be used in severe cases, particularly with paralytic ileus and malignant bowel obstruction for which opioids are generally contraindicated.4,29 Recent reports have implicated the chronic use of all anticholinergics in contributing to impaired cognition within 60 days.30

Local Anesthetics

Local anesthetics have analgesic properties in neuropathic pain related to the blockade of the sodium channel. There are few studies to support their use in cancer pain, but they are widely used in the treatment of musculoskeletal pain. Topical analgesics (including lidocaine 5% patch) have been used as a treatment for PHN, and clinical experience supports their use for other neuropathic pain conditions.

Most topical agents have fewer than 10% systemic absorption. A local anesthetic patch is usually applied 12 hours per day, up to 3 patches, though there are few studies that have shown adverse events with continuous exposure to topical local anesthetics. The most frequently reported adverse event is mild to moderate skin redness, rash, or irritation at the patch application site.10 These agents can be used in conjunction with trigger point injections or nerve blocks and may be used for pre-emptive analgesia. Brief IV infusions at low dose with telemetry monitoring can be administered, or use in intrathecal pumps may be considered if a trial of anticonvulsants or antidepressants has failed.4 Common adverse effects are paresthesias, abnormal taste, tinnitus, blurred vision, drowsiness, but toxic doses may cause seizures and cardiac arrest.

Mexiletine is an oral antiarrhythmic, which is structured similarly to lidocaine, has been used to treat patients with neuropathic pain from numerous etiologies, and is the preferred oral local anesthetic. Unfortunately, mexiletine has a high rate of adverse effects and discontinuation due to toxicity occurring in almost one-half of patients in one study.4

Cannabinoids

Marijuana includes more than 70 chemical compounds including cannabinoids. Formulations include oral (nabilone and dronabinol)—which have a longer duration of analgesic effect—a recently FDA-approved nasal spray (nabiximols), and a sublingual spray in development. They can provide analgesia without respiratory depression31 for an opioid sparing effect,32 have anticonvulsant properties for neuropathic pain,33 and have anti-inflammatory effects for muscle pain or arthralgias by their peripheral effects. Several states have approved dispensaries for selected patients, though marijuana is still considered a schedule I substance by the Drug Enforcement Administration. Cannabinoids have the potential for abuse and dependency as well as weight gain and lower libido.

Capsaicinoids

In cancer patients, capsaicin cream has been shown to be effective in reducing neuropathic postsurgical pain including post-mastectomy pain.4 There are two commercially available concentrations (Zostrix, 0.025% and Zostrix HP, 0.075%), to be applied three to four times daily, as well as a patch (Qutenza, 7%) applied every 3 months for PHN. A trial of several weeks is needed to adequately judge effects. A major side effect is localized irritation, which causes a burning sensation, and limits its use.

Psychostimulants

There is evidence that psychostimulant drugs dextroamphetamine (Adderal, Dexadrine, Vyvanse), methylphenidate (Ritalin), and caffeine have analgesic effects. In cancer patients, methylphenidate can reduce opioid-induced somnolence, improve cognition, treat depression, and alleviate fatigue.4 Treatment typically begins with 2.5 to 5 mg in the morning and again at midday, if necessary, to keep the patient alert during the day and not interfere with sleep at night. Doses are increased gradually until efficacy is established. These are schedule II medications with a risk for dependency, abuse, and withdrawal symptoms, and have cardiovascular toxicity.4 Modafinil (Provigil) and its racemic active isomer, armodafinil (Nuvigil), can be used for opioid-induced sedation,34 narcolepsy, and fatigue (particularly with sleep apnea) and may have adjunctive analgesic effects.35 Use these medications with caution in patients with severe renal disease. They may also cause Stevens-Johnson syndrome.36

Hormonal Therapy

For breast cancer pain, hormonal therapy (tamoxifen, raloxifene) can reduce the risk of osteoporosis and subsequent fractures, and improve cognition.4 Testosterone replacement or anabolic androgens (usually given in topical formulations, and occasionally intramuscularly, with monitoring of liver enzymes) may be required in patients with opioid-induced hypogonadism for improvement of libido, fatigue, muscle mass, osteoporosis, cognition, and wound healing. Male hormones should not be used with prostate cancer, and testosterone levels should be monitored. Leuprolide injections have been used for treatment and reduction of pain in prostate and breast cancer due to its anti-androgenic properties.1

Dopaminergic Agents

Carbidopa and levodopa combination, ropinirole, and pramipexole may be used for neuropathic pain and restless leg syndrome,4 which can be associated with iron deficiency anemia, pregnancy, fibromyalgia, and peripheral neuropathy from diabetes or CT.4 The side effects include nausea, hallucinations, and an increased risk of gambling addiction.

Ziconotide

Ziconotide (Prialt), derived from the cone snail, is a non-habituating intrathecal analgesic agent used to treat severe and chronic pain. It is an N-type voltage-gated calcium channel blocker, which inhibits the release of glutamate, calcitonin gene-related peptide, and substance P in the brain and spinal cord. Its side effects include nausea, ataxia, and psychosis.37

Botulinum Toxin

Botulinum toxin intramuscular injections can be considered for refractory musculoskeletal pain related to muscle spasms including trismus or myokymia occurring after radiation therapy.38 It may also be used for spasticity, uninhibited detrusor contractions, anal fissures, hyperhidrosis, dystonias, and chronic vascular headaches, which may occur as co-morbidities from cancer. It is administered every 3 months, with side effects including an immediate flu-like syndrome, dysphagia or dysarthria (if injected in the neck), and temporary weakness of the injected muscle.

Conclusion

The use of adjuvant analgesics in cancer patients is still often guided solely by anecdotal experience or derived from data on nonmalignant pain. Future studies focused on the cancer population are needed to expand and improve the use of these drugs. Part 4 discusses evaluation and treatment of chemo- and radiation-induced pain.

Last updated on: October 28, 2014
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