Pharmacological pain treatment
(1) Principles. According to the World Health Organization (WHO) guidelines for three-step analgesic treatment for cancer pain, the five basic principles of pharmacological analgesic treatment for cancer pain are as follows.
Oral administration. Oral administration is the most common route of drug delivery. For patients who are not suitable for oral administration, other routes of drug delivery can be used, such as subcutaneous injection of morphine, patient-controlled analgesia, and more convenient methods such as transdermal patches.
Medication should be administered in steps. According to the patient’s pain level, analgesic drugs of different strengths should be selected in a targeted manner.
①Mild pain: non-steroidal anti-inflammatory drugs (NSAID) can be used.
②Moderate pain: weak opioids can be used, and NSAIDs can be used in combination.
③Severe pain: strong opioids can be used and NSAIDs can be used in combination.
The use of opioids together with NSAIDs can enhance the pain relief effect of opioids and reduce the dosage of opioids. Strong opioids may also be considered for mild and moderate pain if good analgesia can be achieved without serious adverse effects. If the patient is diagnosed with neuropathic pain, tricyclic antidepressants or anticonvulsants, etc., should be preferred.
Timed medication. Refers to the regular administration of pain medications at prescribed intervals. Timed administration helps to maintain stable and effective blood concentration. At present, the clinical use of controlled-release drugs is increasingly widespread, emphasizing the use of controlled-release opioids as the base medication for pain relief, and the administration of immediate-release opioids for symptomatic management when titration and outbreak pain occur.
Individualized drug administration. This refers to the individualized drug regimen according to the patient’s condition and the dose of cancer pain relief drugs. When using opioids, there is no ideal standard dose of opioids due to individual differences, and sufficient doses of drugs should be used to provide pain relief according to the patient’s condition. The nature of the neuropathic pain should also be identified and the possibility of combination medication should be considered.
Pay attention to specific details. Patients using pain medication should be monitored more closely, the degree of pain relief and the organism’s response should be observed closely, the interactions of drug combination applications should be noted, and necessary measures should be taken in a timely manner to minimize the adverse drug reactions with a view to improving the quality of life of patients.
(2) Drug selection and use method. According to the degree and nature of pain, the treatment being received and the concomitant diseases of cancer patients, pain relief drugs and auxiliary drugs should be selected reasonably, the dosage and frequency of drug administration should be adjusted individually, and adverse reactions should be prevented and controlled in order to obtain the best pain relief effect and reduce the occurrence of adverse reactions.
Non-steroidal anti-inflammatory drugs. Different NSAIDs have similar mechanism of action and have analgesic and anti-inflammatory effects, and are often used to relieve mild pain or combined with opioids to relieve moderate or severe pain. NSAIDs commonly used in cancer pain treatment include: ibuprofen, diclofenac, acetaminophen, indomethacin, celecoxib, etc.
The common adverse reactions of NSAIDs include: peptic ulcer, gastrointestinal bleeding, platelet dysfunction, renal impairment, hepatic impairment, etc. The occurrence of their adverse reactions is related to the dose and duration of use. The daily restricted doses of NSAIDs are: ibuprofen 2400mg/d, acetaminophen 2000mg/d, celecoxib 400mg/d.
Using NSAIDs, when the dose of medication reaches a certain level or more, increasing the dose of medication does not enhance its pain-relieving effect, but the drug toxicity reaction will increase significantly. Therefore, if long-term use of NSAIDs is required, or if the daily dose has reached the restrictive dosage, replacement with opioid analgesics should be considered; if it is a combination drug, only the dose of opioid analgesics should be increased.
Opioids. It is the drug of choice for moderate and severe pain treatment. At present, the short-acting opioids commonly used in cancer pain treatment are morphine immediate release tablets, and the long-acting opioids are morphine extended-release tablets, oxycodone extended-release tablets and fentanyl transdermal patches. For the treatment of chronic cancer pain, opioid agonists are recommended. For long-term use of opioid analgesics, oral route of administration is preferred, and transdermal absorption route of administration can be used when there are clear indications.
①Initial dose titration. There are large individual differences in the efficacy and safety of opioid analgesics, so it is necessary to gradually adjust the dose to obtain the best dose, which is called dose titration. For patients using opioids for pain relief for the first time, titration should be performed according to the following principles: use morphine immediate release tablets for treatment; according to the degree of pain, draw up an initial fixed dose of 5-15 mg for Q4h; if the pain is not relieved or the relief is unsatisfactory after medication, the titrated dose should be given after 1 hour according to the degree of pain (see Table 1), and closely observe the degree of pain and adverse reactions.
After the first day of treatment, calculate the drug dose for the next day: total fixed dose for the next day = total fixed dose for the previous 24 hours + total titrated dose for the previous day. On the second day of treatment, the calculated next day’s total fixed dose is divided into 6 oral doses, and the next day’s titrated dose is 10%-20% of the previous 24 hours’ total fixed dose. Adjust the dose day by day as indicated until the pain score stabilizes at 0-3. In case of uncontrollable adverse effects and pain intensity 4, a titration dose reduction of 25% should be considered and the condition should be re-evaluated.
For patients with moderate to severe cancer pain who have not used opioids, it is recommended to choose short-acting agents for initial dosing and individualize the titration dose. When the dose is adjusted to the ideal dose level for pain relief and safety, switching to an equivalent dose of long-acting opioid analgesics can be considered.
For patients already using opioids for pain, titration was performed according to the patient’s pain intensity, as required in Table 1.
For patients with relatively stable pain conditions, consider using an opioid controlled-release agent as background dosing, on which short-acting opioids are backed up for the treatment of explosive pain.
② Maintenance medication. Long-acting opioids commonly used in China include: morphine extended-release tablets, oxycodone extended-release tablets, fentanyl transdermal patches, etc. During the application of long-acting opioids, short-acting opioid painkillers should be reserved. When the patient’s condition changes, the dose of long-acting pain medication is insufficient, or when an outbreak of pain occurs, short-acting opioids should be given immediately for relief therapy and dose titration. The rescue dose is 10%-20% of the total amount of medication used in the previous 24 hours. If the number of short-acting opioid rescue doses is greater than three per day, consideration should be given to converting the first 24 hours of rescue dose to long-acting opioid dosing.
Dose conversions between opioids can be made with reference to the conversion factor table (see Table 2). When switching to another opioid, careful observation of the condition and individualized titration of the dose is still required.
If you need to reduce or stop the use of opioids, use the gradual reduction method, i.e., first reduce the dose by 30%, then 25% after two days, until the daily dose is equivalent to 30 mg of oral morphine, and continue to take two days to stop the drug.
③Adverse reactions prevention. Opioid adverse reactions mainly include: constipation, nausea, vomiting, drowsiness, itching, dizziness, urinary retention, delirium, cognitive impairment, respiratory depression, etc.. With the exception of constipation, most adverse reactions to opioids are temporary or tolerable. Prevention and management of opioid analgesic adverse reactions should be an important part of the pain management treatment plan. Most adverse reactions such as nausea, vomiting, drowsiness, and dizziness occur in the first few days of medication in patients who have not used opioids before.
Within a few days of initial opioid use, consider concomitant administration of an antiemetic such as metoclopramide (gastrofacial) to prevent nausea and vomiting, or discontinue the antiemetic if there is no nausea. Constipation symptoms usually continue to occur throughout opioid analgesic treatment, and most patients require a laxative to prevent constipation. Adverse reactions such as excessive sedation and psychiatric abnormalities require a reduction in the dose of opioid medication. The effects of renal insufficiency, hypercalcemia, metabolic abnormalities, and co-administration of psychotropic drugs should be noted during the course of medication.
Adjuvant medication. Adjuvant analgesics include: anticonvulsants, antidepressants, corticosteroids, N-methyl-D-aspartate receptor (NMDA) antagonists and local anesthetics. Adjuvant medications can enhance the analgesic effect of opioids or produce direct analgesia. Adjuvant analgesics are commonly used as an adjunct to the treatment of neuropathic pain, bone pain, and visceral pain. The selection of the type of adjuvant medication and dose adjustment need to be individualized. The adjuvant drugs commonly used for neuropathic pain mainly include.
①Anticonvulsant drugs: used for tearing pain, discharge-like pain and burning pain caused by nerve injury, such as carbamazepine, gabapentin and pregabalin. Gabapentin 100-300mg orally once a day, gradually increasing to 300-600mg three times a day, the maximum dose is 3600mg/d; Pregabalin 75-150mg 2-3 times a day, the maximum dose of 600mg/d.
②Tricyclic antidepressants: used for numbness-like pain and burning pain caused by central or peripheral nerve injury, this class of drugs can also improve mood and sleep, such as amitriptyline, duloxetine, venlafaxine, etc. Amitriptyline 12.5-25 mg orally once a night, gradually increasing to the optimal therapeutic dose.
During pharmacological pain treatment, changes in pain scores and adverse reactions of drugs should be recorded in the medical records to ensure safe, effective and continuous relief of cancer pain.
3.Non-pharmacological treatment. Non-pharmacological treatments for cancer pain treatment mainly include: interventional therapy, acupuncture, physical therapy such as transcutaneous electrical stimulation, cognitive-behavioral training, psychosocial support therapy, etc. Appropriate application of non-pharmacological therapies can be a useful supplement to pharmacological pain treatment and can increase the effect of pain treatment when used in combination with pharmacological pain treatment.
Interventional therapy refers to interventions such as nerve block, nerve release, percutaneous vertebroplasty, nerve destruction surgery, nerve stimulation therapy and radiofrequency ablation. Epidural, intradural and plexus block routes of drug administration can effectively control cancer pain by single nerve block, reduce the gastrointestinal reaction to opioids and lower the dose of opioids. The expected survival time and physical condition of patients, the existence of indications for antitumor therapy, and the potential benefits and risks of interventional therapy should be comprehensively evaluated before interventional therapy.