Table 101 Potential Problems with Opioid Medications

Side Effects

Serious side effects of opioids can include respiratory depression (slowed breathing), so it's recommended that these medications not be used in conjunction with alcohol, antihistamines, barbiturates, or benzodiazepines. (There are exceptions; if you are taking opioids, just be sure to tell your doctor about any other medications you're taking that can be sedating or cause respiratory depression.) Other side effects may include rash or itching, nausea with or without vomiting, constipation, sedation, dizziness, cognitive impairment, and urinary retention.

Tolerance

Tolerance occurs when someone requires an increased dose of medication to experience the same level of pain relief (that is, after many doses, the drug becomes less effective in managing pain).

Physical Dependence

Physical dependence results in symptoms of withdrawal when the medication is abruptly discontinued. It occurs after more than just a few days of continuous use. Physical dependence is usually not a problem as long as patients are told to wean themselves off these medications rather than stopping abruptly. Drug dependence and tolerance are both physical problems. They do not indicate either addiction or abuse.

Addiction

Addiction is characterized by a compulsive use and craving of any substance that is used for mood-altering purposes. Individuals are addicted to opioids (or any other drug) if they (1) lose control over the use of the medication; (2) use the medication compulsively; (3) crave the medication; and (4) continue to take the medication despite the possibility of harm to themselves or others. In other words, addiction is a medical condition that manifests itself as a psychological and behavioral problem.

Abuse

Abuse means using a substance in a way that deviates from approved medical use or social patterns within society. Abuse is subject to cultural disapproval and is often associated with the "recreational" use of substances. Approximately one-third of the U.S. population have used illicit drugs. It is estimated that 6-15 percent of the population has some form of substance-use disorder. People are most familiar with abuse in the context of illegal street drugs; however, estimates indicate that up to 28 percent of controlled substances are abused. Moreover, according to estimates, more than 4 million Americans use prescription drugs for nonmedical purposes. Prescription medications are often "diverted" from legitimate channels to illicit ones via falsified prescriptions.

Table 10.2. Signs of Opioid Withdrawal Compared to Signs of Intoxication

Withdrawal

Muscle cramps

Increase in saliva and tears

Drug craving

Yawning

Bad mood

Enlarged pupils

Gooseflesh

Tremors

Inability to sleep Decreased appetite Vomiting Diarrhea Irritability

Increased blood pressure

Intoxication Insensitivity to pain

Drowsiness Euphoria Mental clouding Constricted pupils Vomiting

Difficulty breathing

Sometimes opioids are used in cancer treatment in conjunction with other medications. For example, if someone has a tumor that is pressing on a nerve, then a medication such as gabapentin, which is in the class of antiseizure drugs but is often used for nerve pain, might be a reasonable option. Other times opioids are used with antidepressant medications that affect serotonin levels or other substances (which help modulate pain) in the brain.

Although opioids are a mainstay in the treatment of pain from a malignancy, there are many other possible medications—some of which not only can alleviate pain but also may slow the growth of the cancer. For example, in many types of advanced cancer, the disease spreads (metastasizes) to the bones. The class of bisphosphonate medications may be helpful in treating the associated pain as well as reducing the risk of fracture, though the current research is far from conclusive and these drugs are not typically given to cancer patients for pain. This class of medications has been used in research studies looking at breast, prostate, and lung cancer as well as myeloma (bone marrow cancer) and other cancers. One study was done on the use of a bisphospho-nate called zoledronic acid in men with prostate cancer that had spread to the bones. It was found that this drug helped to reduce bone loss, thereby reducing associated disease complications (for example, fractures) and pain. The same study showed that men with early prostate cancer that had not spread to the bones might benefit from this drug as well. According to the authors, "preclinical evidence suggests that bisphosphonate treatment of early-stage prostate cancer may reduce the incidence of bone metastases."

There are many other ways to treat cancer pain, thereby enhancing the person's quality and possibly even length of life. For example, external beam radiation and surgery are treatments that can shrink tumors. Radiopharmaceuticals, though not commonly used for bone pain, are drugs that can be administered intravenously and may be an option for someone with cancer in the bones. Corticosteroid injections in the spinal region or other areas can help to alleviate pain. The list of options is extensive and continually expanding. Appropriate treatment depends on the type and stage of cancer as well as the areas affected and the associated pain symptoms. Patient and physician preference for a particular treatment choice is also an important consideration.

The use of cannabinoids (such as marijuana) in the treatment of cancer has received quite a bit of press. It is estimated that there are 150 million nonmedical cannabis users worldwide. The number of people with cancer who use cannabis is not known but is much smaller. Cannabinoids have been shown to be helpful treatments in cancer and can improve appetite, reduce nausea and vomiting, and alleviate pain. When cannabis is used medically, it may take various forms; often it is dissolved in sesame oil and then swallowed in gelatin capsules. Can-nabinoid smoke may be a risk factor for respiratory cancers, so this form is not used. In the United States, marijuana is classified under the Controlled Substances Act of 1970 as a drug that has no medical use. One way that Americans may gain access to the drug, however, is to participate in clinical trials where cannabinoids are used.

Although smoking marijuana is not legal, the Food and Drug Administration has approved two pill forms of cannabinoids. The following information is from the FDA's Web site (www.fda.gov/ola/2004/ marijuana040i .html):

FDA has approved two drugs, Marinol and Cesamet, for therapeutic uses in the U.S., which contain active ingredients that are present in botanical marijuana. On May 31, 1985, FDA approved Marinol Capsules, manufac tured by Unimed, for nausea and vomiting associated with cancer chemotherapy in patients that had failed to respond adequately to conventional antiemetic [anti-nausea] treatments. Marinol Capsules include the active ingredient dronabinol, a synthetic delta-9-tetrahydrocannabinol or THC, which is considered the psychoactive component of marijuana. On December 22, 1992, FDA approved Marinol Capsules for the treatment of anorexia associated with weight loss in patients with AIDS. Although FDA approved Cesamet Capsules for the treatment of nausea and vomiting associated with chemotherapy on December 26, 1985, this product was never marketed in the U.S. Cesamet Capsules contain nabilone as the active ingredient, a synthetic cannabinoid. Nabilone is not naturally occurring and not derived from marijuana, as is THC.

Although several states have passed legislation allowing the medicinal use of cannabinoids, the federal government still prohibits it, with the exception of Marinol. The federal government can prosecute people who use other forms of cannabinoids. Canadians who are eligible to use these drugs can obtain them from their government or grow their own.

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