Page 31 Complete Your CE Test Online - Click Here nausea, liver function abnormalities, bleeding complications, and congestive heart failure, especially in high-risk groups [203]. Opioids are used to relieve moderate to severe pain. Opioids work to relieve moderate to severe pain, i.e. step 2 on the WHO scale [145]. Some patients with cancer pain cease receiving pain relief from opioids after a time due to tolerance. Larger doses or a different opioid may be needed if this happens. Tolerance of an opioid reflects physical dependence, and is not the same as addiction (i.e. psychological dependence, in which the patient takes a drug for its euphoric effects). Opioid doses can be safely increased as needed for pain without causing addiction. There are several types of opioids: ● ● Buprenorphine. ● ● Codeine. ● ● Diamorphine. ● ● Fentanyl. ● ● Hydrocodone. ● ● Hydromorphone. ● ● Methadone. ● ● Morphine (the most commonly used opioid for cancer pain). ● ● Oxycodone. ● ● Oxymorphone. ● ● Tapentadol. ● ● Tramadol. Methadone is safer for patients with renal failure, and is preferred for those with known opioid allergies because it is synthetic. However, methadone also has disadvantages, including drug interactions, the risk of QT prolongation (an EKG is recommended before starting and 2-4 weeks after starting treatment), and a variable equianalgesic ratio, making rotation (opioid switching) more challenging. Methadone is metabolized by CYP 3A and CYP 2D6. CYP 3A inducers (e.g. certain anticonvulsants and antiretroviral agents) can potentially reduce analgesic effect. These are just some of the reasons why it should only be prescribed by experienced clinicians [145]. Codeine requires metabolism by CYP 2D6 into its active form. People with low CYP 2D6 activity may get poor relief from codeine, but people with high CYP 2D6 activity are rapid metabolizers who can quickly reach toxicity with normal doses. Patients started on codeine should be monitored for pain relief and toxicity until effects are assured [203]. Meperidine is notably missing from this list because it has a neurotoxic and cardiotoxic metabolite, normeperidine, with a long half-life, and cancer pain requires repeat dosing over time. Thus it is contraindicated for chronic pain. Butorphanol and pentazocine are mixed agonist- antagonist drugs and are also not recommended for treating cancer pain because switching from a pure opioid agonist drug could precipitate withdrawal crisis and subsequent difficulty getting pain back under control [203]. Most patients with cancer pain will need to receive opioids on a regular schedule. Receiving opioids on a regular schedule helps control the pain. The dose interval depends on which opioid is being used and occurrence of breakthrough pain. The dose is slowly adjusted until there is a good balance between pain relief and side effects. Outpatients and their family caregivers must know how to safely use, store, and dispose of opioids [146]. The following are the most common side effects: ● ● Constipation. ● ● Nausea. ● ● Drowsiness. ● ● Dry mouth. Drowsiness and nausea most often occur when opioid treatment is first started; these patients usually become better within a few days [146]. Other side effects of opioid treatment include the following: ● ● Vomiting. ● ● Hypotension. ● ● Dizziness. ● ● Insomnia. ● ● Confusion. ● ● Delirium or hallucinations. ● ● Trouble urinating. ● ● Problems with breathing. ● ● Severe itching. ● ● Problems with sexual function. ● ● Hot flashes. ● ● Depression. ● ● Hypoglycemia. Teach the patient and family what to watch for and report. Bothersome or severe side effects may require a decreased opioid dose, change to a different opioid, or change in route to help decrease the side effects [146]. Vomiting occurs in about one-third of patients who take opioids; twice as many have nausea. Antiemetics, such as metoclopramide, may be used preventively; prochlorperazine, promethazine, and olanzapine can be used as well. Constipation is common and a scheduled stimulant laxative is typically started along with opioid treatment unless there is a problem with bowel obstruction or diarrhea, along with encouragement to exercise and take in sufficient fiber. The goal is one bowel movement per day, and the regimen may need to be changed to meet that. Significant respiratory depression can usually be avoided through careful titration of doses. Delirium is linked to opioids but is usually multifactorial and not caused by the opioid. In the event of uncontrolled pain at maximal doses, or neurotoxicity such as myoclonus, hallucinations, vivid dreams, confusion, or tolerance (i.e. less pain relief with the same dose over time), opioid rotation (switching) may be helpful. Adjuvant drugs may be given along with opioids to optimize pain relief. These drugs can potentiate opioids, help with symptoms or relieve certain types of pain [145,203,146]: ● ● Antidepressants (such as venlafaxine, duloxetine, desipramine, nortriptylene) for neuropathic pain. ● ● Anticonvulsants may also help neuropathic pain. ● ● Gabapentin and pregabalin, for neuropathic pain. ● ● Local anesthetics for procedural pain. ● ● Corticosteroids in conjunction with opioids (although evidence is weak). ● ● Stimulants during the day, to help with opioid-induced sedation. ● ● Bisphosphonates and denosumab for bone metastases. There are big differences in how patients respond to these drugs, and side effects are common. Some patients have too many side effects from drugs or have pain that needs to be treated in a different way. Other treatments in these cases include [146]: ● ● Nerve block is a procedure in which either a local anesthetic or a drug is injected into or around a nerve to block pain that cannot be controlled in other ways. Nerve blocks may also be used to find where the pain is coming from, to predict how the pain will respond to long-term treatments, and to prevent pain after certain procedures. ● ● Surgical neurologic treatments can be done by inserting a device that delivers drugs or stimulates the nerves with mild electric current. In rare cases, surgery may be done to destroy a nerve or nerves that are part of the pain pathway. ● ● Cordotomy is a less common surgical procedure that is used to relieve pain by cutting nerves in the spinal cord. This blocks pain and other sensation. This procedure may be used for patients who are near the end of life and have severe pain that cannot be relieved in other ways. ● ● Palliative care team consultation: These providers typically work in teams that include doctors, nurses, mental health specialists, social workers, chaplains, pharmacists, and dietitians. Some of their goals are to: ○ ○ Improve quality of life for patients and their families. ○ ○ Manage pain and non-pain symptoms. ○ ○ Support patients who need higher doses of opioids, have a history of substance abuse, or are coping with emotional and social problems. Radiation therapy Radiation therapy is used to relieve pain in patients with skin lesions, other tumors, or bone metastases. Palliative radiation therapy may be given as local therapy directly to the tumor or to larger areas of the body. Radiation therapy can help shrink tumors that are causing pain and may help patients with bone pain move more freely and with less pain [146]: