Cancer pain is a universal problem, and effective analgesic treatment is one of the four priorities of the World Health Organization’s Comprehensive Cancer Programme, which was launched in 1982 to achieve the goal of “making cancer patients pain-free and improving their quality of life by the year 2000”. In 1991, the Ministry of Health issued a notice on the implementation of the “three-stage analgesic treatment program for cancer patients” in China, as well as five basic principles for the clinical application of analgesics.
The so-called three-step approach to cancer pain treatment is to select analgesics of different strengths according to the patient’s pain level and cause after a proper assessment of the nature and cause of cancer pain.
The drugs in the first step are NSAIDs, represented by aspirin, and other drugs such as acetaminophen, ibuprofen, diclofenac, hypericin, naproxen, and indomethacin suppositories (intra-anal) (see Chapter 7 for drugs for skeletal muscle and rheumatic immune diseases). These drugs are mainly used in patients with mild to moderate pain, but can also be used as adjuncts to the second and third steps.
The second-order drugs are weak opioid analgesics, represented by codeine and other drugs such as dihydrocodeine, aminoglutethimide, hydrocodone, oxycodone, bupropion, and tramadol. These drugs are mainly used for patients with moderate pain or those who still have pain after the first step of medication.
The drugs in the third step are strong opioid analgesics, represented by morphine and other drugs such as hydromorphone, hydromorphone, levorphanol, dihydroetorphine, methadone and fentanyl. These drugs are mainly used for patients with severe pain or patients whose pain cannot be relieved even after applying the drugs of the second stage.
1.The main principles of cancer pain drug treatment
(1) Oral administration: Oral administration is preferred. Oral administration is economical and convenient, especially for strong opioid analgesics, which is not easy to produce dependence, so that it is convenient for patients to use the drugs for a long time. If oral administration is not suitable or the pain relief effect cannot be achieved, transdermal patches, anal administration and infusion pumps can be used for continuous subcutaneous administration.
(2) Timely dosing: Regularly administer the drug on time according to the effective action time of the drug, rather than on demand, so that the patient can maintain a constant effective blood concentration to achieve the purpose of making cancer patients pain-free.
(3) Drug administration according to a step.
(4) Individualized dosing: The dose of the drug used should be based on the effective analgesia of the patient, and should not be based on the conventional dose recommended by various analgesic drugs, nor should it be limited by the “extreme amount” specified in the pharmacopoeia. On the one hand, there are individual differences in drug effects; on the other hand, in the process of long-term use of opioids, the tolerance of each person is different, and the adjustment of dose may also be different.
(5) Pay attention to the treatment of other problems: problems that often occur during the treatment of cancer pain patients, such as insomnia and depression, adverse reactions to various analgesics, and supportive treatment, should be handled appropriately.
2.Several issues need to be clarified
(1) Patients have developed tolerance or physical dependence on opioids, not the same as having become addicted to patients taking opioids for a long time, tolerance or physical dependence may occur, and people often wrongly categorize these reactions as the kind of mental dependence (addiction) caused by drug abuse. This misconception often leads physicians to fail to properly use opioids for cancer pain control. In fact, opioids used clinically for cancer pain control are mainly in controlled and extended release formulations, administered orally or transdermally, and administered on time. These methods can avoid excessive peak blood concentrations and follow standardized treatment, and the risk of drug dependence (addiction) is minimal. Drug tolerance is common in cancer pain treatment and does not affect the patient’s continued use of opioid analgesics. It is necessary to increase the dose of opioid drugs according to the needs of the disease.
(2) Use of pethidine: Pethidine is used for acute pain and short-term analgesic treatment, and is generally not used for cancer pain. This is because, on the one hand, its analgesic effect lasts for a short time (2.5-3.5 hours); on the other hand, its toxic metabolite, norethindrone, tends to accumulate in the body, thus causing symptoms of central nervous system toxicity, such as seizures and convulsions, and is more likely to produce toxic symptoms when the kidney is not functioning well.
(3) Precautions for clinical application of opioids: (1) The presence of moderate pain should be applied early, with sufficient dose, and often adjust the dose according to the condition. (2) The application of opioid drugs should also pay attention to the prevention of adverse reactions. ③Increase the dose of single dose when the pain increases, rather than increasing the number of doses. ④People receiving immediate-release morphine treatment may double the dose at bedtime to prevent pain from disturbing sleep. ⑤ Controlled-release tablets should not be crushed. (6) When applying opioid treatment, there should be a record of pain intensity and dose titration.
(4) Controlled and slow-release preparations: morphine controlled-release tablets, the effect lasts 8-12 hours. Long-acting fentanyl patch: (1) administered through the skin, drug absorption does not go through the gastrointestinal tract, to avoid the first pass effect, high bioavailability, reduce the adverse reactions of the liver. ②Long duration of drug action (2-3 days), reduce the number of dosing, improve patient compliance, and not easy to develop tolerance. (③) Slow and smooth release of drug, low blood concentration, not easy to reach peak, not easy to cause abuse. The following issues should be noted in the use of transdermal patches: (1) the application site is the front chest, back, upper arm and inner thigh; (2) the application site should be pressed for 30 seconds after the patch; (3) the application site should be scrubbed with water before the patch is applied, and alcohol that can denature the membrane should not be used; (4) the patch takes effect 6 to 12 hours after the patch is applied, and an immediate release agent should be applied on the first day of application.
(5) Methods to reduce drug tolerance: (1) Apply adjuvant drugs to enhance analgesic effect as much as possible; (2) Apply different types of analgesic drugs alternately instead of using one drug from the beginning to the end; (3) After the patient’s pain is reduced, the drug dose can be adjusted gradually after several days, and the drug interval can be extended appropriately; (4) Cooperate with other pain relief methods and drug delivery routes.
(6) New concept of three-step treatment for cancer pain: The main reason why the goal of pain-free cancer patients in 2000 proposed by WHO has not been achieved is that the mechanism of cancer pain is very complicated and there are limitations in using drug treatment alone, therefore, scholars at home and abroad advocate adjusting the concept of three-step treatment for cancer pain. ① For patients categorized as the first and second step according to the WHO stepwise sub-program, the new view is to control moderate pain early with small doses of strong opioids. ② Patients classified as second and third order have more complex pain mechanisms, some of which also involve nerve and tissue r organ damage, especially in patients with neurogenic pain. The new progress is the use of adjuvant medication for relief after the standardized and adequate use of opioid analgesics, in which the study of antidepressant and anticonvulsant drugs is the focus. ③ Due to the limitations of cancer pain medication, there will be 10% to 20% of patients who finally cannot get effective pain control after receiving standardized analgesic treatment. Minimally invasive treatment, such as nerve block, nerve destruction and local treatment of lesions, can be considered for these patients. However, such procedures may cause corresponding neurological dysfunction and have the possibility of failure at a later stage; therefore, fewer patients are clinically suitable for these treatments. At present, a relatively advanced interventional treatment method recognized internationally is intrathecal drug infusion therapy, whose principle of action is to infuse pain-relieving drugs into the subarachnoid space through a computerized infusion pump buried in the body, which acts on the action sites of the spinal cord to achieve pain relief. It not only can relieve pain more effectively, but also can reduce the adverse effects of morphine and other drugs, and improve the quality of life of cancer patients.
3.Assessment of pain
The main reason for the failure of cancer pain treatment is often due to the failure to properly assess the patient’s pain situation. Assessment of pain requires close cooperation between clinicians and patients.
After treatment starts, pain should be assessed regularly and regularly. When a new pain lesion appears, it should be reported at S time. Determine the interval of pain assessment according to different cancer pain treatment protocols. For example, non-intestinal administration method should start assessment 15-30 minutes after drug administration; oral administration method should start assessment 1 hour after drug administration. Determine the cause of pain and decide the pain treatment plan.
(1) Pre-treatment assessment: The purpose of this is to understand the nature of the patient’s pain such as the site, degree and cause of pain. The assessment includes the following: detailed medical history; physical examination; psychosocial assessment; and clarification of the diagnosis.
(2) Assessment during treatment: During the course of pain treatment, the pain situation needs to be continuously assessed. When the pain changes or new pain lesions appear, a diagnosis should be made and the pain treatment plan should be modified in a timely manner.