What are cancer pain management medications?

Cancers diagnosed or treated: Medications and other therapies that control pain symptoms are used in patients with any type of cancer; types of treatment depend on the type of pain experienced, which can be determined by the type of cancer or type of treatment (chemotherapy, radiation, surgery) used.

Subclasses of this group: Numerous classes of drugs are useful in the treatment of cancer pain, including nonopioid analgesics, opioid analgesics, tricyclic antidepressants, and anticonvulsants.

Delivery routes: These drugs may be administered orally in tablets, capsules, or solutions; topically as patches, creams, or intranasal sprays; rectally as suppositories; submucosally as lozenges; or intravenously, intramuscularly, or subcutaneously as injectable solutions and suspensions. The drugs may be administered in outpatient, inpatient, or drop-in clinic settings.

How these drugs work: Cancer pain has historically been a cause for concern in patients and caregivers alike. The treatment of pain as a whole and in cancer patients is often poorly or inadequately managed, despite numerous available treatment options. Implementation of pain management guidelines and increased awareness of health professionals about the role of pain and the importance of pain assessment in cancer therapy, however, have improved the control of many types of cancer pain.

Different types of pain require different forms of treatment. Two main types of pain include nociceptive pain resulting from actual damage to or inflammation of a tissue or organ (visceral pain) or to bone (somatic pain) and neuropathic pain, which results from nerve damage or compression. Any source of pain may cause acute, chronic, or breakthrough pain.

Nociceptive or neuropathic pain occurring in the cancer patient may result from various sources, all with differing mechanisms. Approximately 75 percent of cancer-related pain results from the tumor itself because of invasion or compression of soft tissue, bone, or nerves. Another 20 percent results from treatments such as radiation, chemotherapy, and surgical biopsy, all of which can be associated with mucositis, neuropathy, infection, and other complications.

Although many options are available to control cancer pain, pharmacologic therapy is the primary, most successful method. Other options include removal of cancer in patients whose tumor compression is the pain source; neurosurgical treatments such as epidural blocks in patients whose pain is not adequately controlled with other options; complementary therapies such as relaxation techniques, massage, and transcutaneous electrical nerve stimulation (TENS); and psychological treatments that include behavioral or lifestyle changes and support groups.

Analgesic pharmacotherapy and adjuvant medications are primarily used to control cancer pain, and most patients experience pain severe enough to require opioid analgesia. Pain falls into many categories, which then dictate treatment options. These categories include mild-to-moderate pain, moderate-to-severe pain, breakthrough pain, and neuropathic pain. Most types of pain in cancer patients are considered chronic, with only breakthrough pain being an acute situation that requires quick-acting relief.

Mild-to-moderate pain may be relieved with nonopioid medications; aspirin, acetaminophen, and ibuprofen or other
nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary options. Nonopioid analgesics act primarily on the peripheral nervous system to reduce pain or inflammation at the tissue, organ, bone, or incision site. The anti-inflammatory activity of NSAIDs is useful in particular for bone pain, muscle compression, and some tissue pains from swelling.

Moderate-to-severe pain often requires opioid analgesic therapy. Drugs in the opioid class include oxycodone, propoxyphene, hydrocodone, morphine, hydromorphone, meperidine, and fentanyl. Opioids work in the central nervous system by binding to pain receptors, namely mu, kappa, and/or delta, to induce analgesia. Opioids fall into three categories of activity: pure agonists (such as morphine, codeine, fentanyl, hydromorphine, oxycodone, methadone), pure antagonists (such as naloxone) used to reverse opioid toxicity but without their own analgesia, and mixed or partial agonists/antagonists (such as pentazocine, butorphanol, buprenorphine) that are used in more acute settings because of limited analgesic activity. Pure receptor agonists are primarily used for the control of chronic pain. Most opioid agonists are mu or kappa receptor-selective, although individual agents may have varying amounts of activity at the two receptor subtypes and can be synergistic with each other. Because each opioid agonist interacts uniquely and to differing degrees with mu and kappa receptors, and because patient response to each drug varies, substitutions within the class should be considered before giving up on opioid therapy when pain control is incomplete.

Cancer patients often require high doses of opioids for long periods of time. Important considerations in the long-term management of pain using analgesic therapy are tolerance, withdrawal, addiction, inadequate control, and breakthrough pain. Psychological dependence, or addiction, is uncommon with the appropriate use of opiates, even when doses are increased in response to tolerance. Although the mechanisms driving opiate tolerance are unclear, dosage increases usually improve tolerance of a single agent and are limited only by side effects. Although withdrawal symptoms are possible as a result of physical dependence, tapering doses in reverse often ameliorates these concerns. Adequate control is difficult because of the highly subjective nature of pain. Patients respond differently to pain and to pain medications, and they often fail to report inadequate relief because of personal concerns about dependence or addiction. Communication between health care professionals and patients, however, often resolves this concern, and patients become comfortable with around-the-clock pain control.

Breakthrough pain, or pain that occurs despite existing pain medications, usually requires a quick-acting, short-acting secondary medication (such as immediate-release morphine tablets or submucosal fentanyl) to provide relief.

Opioids do provide confirmed relief of peripherally mediated neuropathic pain as well. Adjuvant therapies also play a large role in the treatment of specific pain situations, including neuropathic pain. Common adjuvant drug classes used for neuropathic pain control include tricyclic antidepressants, anticonvulsants, benzodiazepines, and corticosteroids. Tricyclic antidepressants (such as amitriptyline, nortriptyline, and desimpramine) provide established analgesic effects for chronic neuropathic pain through monoamine-related pain-modulating systems in addition to and often prior to the separate relief of depressive symptoms by neurotransmitter alterations. Anticonvulsants (such as phenytoin, valproate, carbamazepine, and clonazepam) usually provide analgesia through the reduction of neuronal excitation or abnormal discharge. Benzodiazepines (such as diazepam and midazolam) have established benefits, through psychotropic and muscle-relaxant activity, in the treatment of neuropathic pain, and they reduce anxiety and associated muscle spasm. Finally, corticosteroids (such as dexamethasone) provide nonselective analgesic effects that are useful for malignant, advanced pain at long-term, low doses and for severe, unresponsive neuropathic pain at short-term, very high doses. Steroids also have nonanalgesic anti-inflammatory benefits that reduce tumor-associated swelling.

Side effects: Because of the varied treatments used to control cancer pain, side effects also differ. General concerns include breakthrough pain, medication tolerance, and withdrawal symptoms. Withdrawal symptoms vary with medication choice and length of use but include rapid breathing, yawning, perspiration, agitation, increased heart rate, muscle twitching, and loss of appetite.

Nonopioid analgesics are not associated with dependence, tolerance, or addiction, although all have a maximum analgesic dose. Select concerns with these agents include liver function damage with acetaminophen and gastrointestinal disturbances or damage with aspirin and NSAIDs.

Opioid side effects include constipation (which can be prophylactically treated with stool softeners), nausea, vomiting, pruritus, and sedation. Respiratory depression is possible in patients with decreased pulmonary function. Many side effects can limit the potential use of a particular opiate but do not rule out the entire class, because the side effects (like the analgesic effects) are linked to specific mu and kappa receptors. For example, constipation and respiratory depression are linked to mu receptor activity.

Adjuvant side effects vary drastically; overlapping toxicities are a primary concern, because adjuvant medications are often combined with each other or with opioids to provide pain relief.

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