JU Medicine



Pain Management:Pain management is a human rightIntroduction:Pain is very prevalent, it increases with ageThe earlier the control, the less severe it will become, and possible irreversible consequences might be prevented50-90% of advanced cancer patients have moderate to severe painAdequate control is possible in >90% of cases if approached systematically Pathophysiology: It can be divided into acute or chronic painNociception: the detection of obnoxious stimuli by special nerve endings. The stimuli are external, they can be mechanical, chemical or thermalThe pathway starts with a stimulus acting on the nerve ending, the impulse is transmitted via both slow (C type) and fast (B gamma) axons to the dorsal horn of the spinal cord. Ascending pathways converge in the thalamus, which acts as a relay to the cortex and other brain centres, like the hypothalamus. Nociceptive pain:The pain that results from stimulating a normal nerveCan either be somatic (from the musculoskeletal system, it is well localised and aching) or visceral (from the rest of the body, it is vague, diffuse and colicky)Tissue damage results in painThe main arm of treatment is opioids (they act more in visceral pain) with additional adjuvants (see later).Neuropathic pain:Results from a primary lesion in the central or peripheral nervous system Disproportionate with the injury (either greater than or less than the extent of the injury)Burning, tingling and shooting in natureOpioids are also the main arm in treatment, with the use of adjuvants.Total pain:The four aspects of pain combined: physical, social, psychological and spiritualPhysical aspect: as in decreased mobility, altered quality of life, and associated symptoms. It needs analgesiaSocial aspect: as in the loss of the job, education, or losing the ability to care for the familySpiritual aspect: as in the loss of the meaning to live, depression, anxiety and the fear of deathPsychological aspect: as in depression and anxietyPain assessment: Pain is subjective. It may be assessed using numerical, picture-based (e.g. faces) or verbal (mild, moderate, sever) scalesTools include Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), Numeral Rating Scale (NRS) and the Brief pain inventory (to assess total pain)Best tool is the numerical scale, 0-10, where 0 means no pain and 10 means worst pain ever.Pain management: Start with pain assessment, and repeat it, pain assessment is an ongoing processManagement includes pharmacological and non-pharmacological methodsNot managing pain may result in CNS changes, and persistence or amplification of the pain The underlying cause is always addressed, but never delay pain management for the sake of treating the causeClear communication with the patient and their family is essential Placebo?Always believe the patient, never assume that the patient is exaggerating Never use placebo as pain management, it is unethical Pharmacological intervention:Drug classes are: non-opioids, opioids and adjuvants Targets include the cerebral cortex (opioids and hypnotics), the brain stem and spinal cord (opioids) and the nerve endings (NSAIDs and steroids)The WHO has recommended a step-wise approach in the management of pain, the 3-step ladder approach. A fourth step is added to include interventional pain management. Step 1:For mild painUse acetaminophen, NSAIDs and aspirin + adjuvants Acetaminophen: Start with it in mild painDose: 4g/d (2x 500mg tablets q 6 hours)Duration of action is 4-6 hours Hepatotoxic (develops at around 20g in a normal liver, however, any patient may have an underlying liver damage, especially in alcoholics, hence, a maximum dose of 3-4g is safe)NSAIDs:Consider renal and GI toxicity Each agent has a ceiling doseIbuprofen: dose 2.4g/d, duration is 8 hours. Available in 200, 400 (2x3), 600 and 800 (1x3) mg tablets. Use a smaller dose if gastric intolerance. Step 2:For moderate painUse weak-moderate opioids (tramadol, codeine, meperidine) + adjuvants (including acetaminophen and NSAIDs)Available options:Acetaminophen 500 + codeine 10 (Rivacod 500/10)Acetaminophen 500 (or 350 or 650) + oxycodone (stronger than codeine): Tylenol 1 (500/10), Tylenol 2 (500/20), Tylenol 3 (500/30) and Tylenol 4 (500/60)Tramadol Step 3: For severe painUse strong opioids: morphine, fentanyl, methadone, hydromorphone, oxymorphone and oxycodone Examples:If mild pain, start with step 1, if severe pain (especially cancer pain), start with step 3Cancer pain: Causes include: tumour itself, chemotherapy, surgery or other comorbidities (DM, osteoarthritis, etc.)Legally, you are allowed to prescribe 3 days of opioid supply. However, in cancer patients, 10 days of opioids is allowedOpioids:They act on the opioid receptors: mu, kappa and deltaThey are conjugated in the liver to a soluble form, excreted via the kidney, at first order kinetics. Adjust the dose in cases of liver or kidney disease (e.g. dehydration) by reducing the dose and/or increasing the dosing interval.IV route is the fastest onset, oral routs has prolonged activity, subcutaneous routs is intermediate Morphine:Natural opioidThe first-choice opioid. It is cheap and very effective. Acts both centrally and peripherally. It is also well-absorbed.Half-life is 3-4 hours, steady state is reached in 4-5 half-livesOral: 30-60 minutes for onset, 2-4 hours for duration (long acting opioid)Subcutaneous: 20-30 minutes for onsetIntramuscular: Do not use it, it is very painfulIntravenous: 6 minutes for onset. Used in patient-controlled analgesia PCA: the patient chooses to receive an IV push of morphine, at least every 6 minutesMethadone:Long acting, but differs from morphineIt has a variable half-life (8-12 or 24 hours), and it needs expert monitoringCodeine:Tablets or syrup (anti-tussive syrup)Also used as anti-diarrheal (opioids slow gut motility, can cause constipation)Oxycodone:Stronger opioid, semisynthetic opioid alkaloid 1.5x morphine effect, more expensive though Used as second line opioid after morphine Available in oral form, pure or combined with acetaminophen or NSAIDsIt is the first line opioid (instead of morphine) in the elderly, in hepatic or renal failureHydromorphone: 5-10x morphine, depending on routeMeperidine (pethidine): it is not recommended in chronic pain, because it is very toxic, not very effective and highly addictiveFentanyl:A strong and very short acting opioid Sublingual, spray and lollipop fentanyl: in breakthrough painIV: in operative anaesthesiaTransdermal patch: long-acting form, 12 hours for onset, 48-72 hours half-life. 12 micrograms or 25 micrograms/ hour, 25 microgram fentanyl is equivalent to 50-60 mg of oral morphine in 24 hours, in other words, the fentanyl transdermal patch is equivalent to a high-dose morphine regimen.Oral opioid dosing:Immediate-release: used initially. Increase dose by 25-50% in case of persisting mild-moderate pain, and increase by 100% in case of severe pain Extended-release: every 8, 12 or 24 hours. Useful as long-term management, not for rapid titration.Breakthrough dosing:For example: a patient is on long-acting opioid therapy (for example at 10mg/12 hours), if they develop pain (breakthrough pain) you use a rapid acting opioid as a rescue management Prescription of opioids in chronic pain: it contains 3 components: Baseline morphine: for example: 10mg q 8-12 hours (extended release)Breakthrough (PRN): 10% of the daily dose (if daily dose is 20mg, breakthrough dose is 2mg)LaxativesNotes: Extended-release morphine cannot be used in a feeding tube, once you break the tablet it becomes immediate release (it loses the extended release ability). In this case, you may use a fentanyl transdermal patch or immediate-release morphineThe use of breakthrough doses has to be recorded in a diaryEqui-analgesic doses:The dose of the opioid equivalent to a given dose of morphine as a referenceDoses equivalent to 15mg of oral morphine: 4mg hydromorphone, 10mg oxycodone, 15mg hydrocodone, and 100mg codeine. Issues with opioid use:Addiction: Psychological dependence: loss of control over drugIf appropriately used (the right dose, for the right patient in the right time), there is no fear of addictionAddiction is very rare if the pain is genuine Cross-tolerance:This means that different opioids can induce tolerance to each other, since they act on the same receptorsIn rotating opioids (periodically changing the opioid for long-term treatment) give 70% of the opioid dose as you switch, since the receptors are already occupied with the previous agentIV dosing:In opioid-na?ve patients (those who are not receiving opioids yet) start with a low dose (2-3mg IV bolus) and then taper If the patient is already on-opioids, give them the IV equivalent of their oral dose (e.g. morphine 5mg IV, 1.5mg hydromorphone IV, 60mg codeine are all equivalent to 15mg morphine PO)Tolerance: with time, the dose needed will increasePhysical dependence: result in withdrawal if stopped abruptly, you should taper the weaning Adverse drug reactions of opioids:Common:Constipation: has to be prevented with laxatives, there will be no tolerance Dry mouth Nausea and vomiting: may need an anti-emetic, tolerance develops in 3-7 daysSedation: tolerance in 3-7 daysSweatsUncommon: there is no tolerance, switch to another opioid if any develops CNS: seizure, hallucinationsPruritisRespiratory depressionUrine retention Allergy: anaphylaxis, bronchospasm or urticaria Adjuvants (co-analgesics):Agents used to supplement analgesia in all steps of management Benefits: Enhance effectReduce analgesic doseUseful in cases of incomplete response to opioids Include: anti-depressants, anti-seizure drugs, anti-NMDA receptor, NSAIDs, acetaminophen and steroidsUsed in: neuropathic pain, muscular spasms, bone pain, liver capsule pain, bowel and bladder spasm, and anorectal pain Neuropathic pain:Harder to control than nociceptive pain, opioids alone are not enoughIn non-cancer neuropathic pain, you may start with an adjuvant agent alone: GABA agonists (gabapentin, pregabalin) + carbamazepine, benzodiazepine, valproic acid, or a tricyclic antidepressant (amitriptyline, imipramine)Steroids:Very effective with opioidsDexamethasone is usually used, particularly in bone pain or liver capsule pain (by shrinking hepatic oedema) and in bowel obstruction Bone pain:Use: NSAIDs, steroid, calcitonin and bisphosphonate + one opioid (in case of cancer metastasis, or in spinal canal stenosis or desk prolapse). You may not use opioids in non-cancer bone pain. Anticholinergics: useful in anorectal pain and bladder spasmMuscle relaxants: in muscle spasmsNon-pharmacological management: Medical and surgical treatmentIncludes treating the underlying causeIncludes: neurostimulation, acupuncture, anaesthesia, physical occupational therapy, psychotherapy, complementary medicine Barriers to pain management:Physician factors:Lack of knowledge, skills or attitude Fear of opioids (fear of addiction, tolerance, adverse reactions, death)Regulatory oversightPatient factors:Fear of opioids Culture: as in cultures than encourage tolerating pain ................
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