The science behind the pills that manage pain
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The science behind the pills that manage pain

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The science behind the pills that manage pain

The science behind the pills that manage pain

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The science behind the pills that manage pain The science behind the pills that manage pain Document Transcript

  • The science behind the pills that manage pain We all feel pain differently, depending on the severity of the injury or ache, as well as our health and our pain threshold. When you are in pain, nerve endings transmit the pain signal to the brain via the spinal cord. The brain then interprets the level of pain. There are two key types of painkillers that are commonly used. The first include ibuprofen and paracetamol, which block the body’s ‘prostaglandins’ (chemicals that produce swelling and pain) at the source of the pain, reducing swelling in the area and reducing the intensity of pain. These ‘aspirin medicines’ are used frequently for mild to moderate pain, but they can only work up to a certain intensity of pain. There are different types of painkillers within this group, such as anti-inflammatory medicines, like ibuprofen, which are commonly used to treat arthritis, sprains and strains. Aspirin is used to help lower the risk of blood clots when used in a low dosage, as they thin the blood. Paracetamol is what’s known as an analgesic, which is used for reducing pain and lowering a temperature. The second type of painkillers include morphine and codeine (narcotic medicines), which block the pain messages in the spinal cord and the brain. This is for much more severe pain. As both types of painkillers use slightly different methods to treat pain, they can be combined, such as in co-codamol, which blends codeine and paracetamol.
  • Pain Medications: Dosage and Indications MEDICATION STANDARD DOSAGE COMMENTS Abbreviations: CrCl = creatinine clearance; GI = gastrointestinal; HIV-SN = HIV sensory neuropathy; LBP = low back pain; OA = osteoarthritis; PN = peripheral neuropathy; TCAs = tricyclic antidepressants Acetaminophen 1 g Q6H PRN or 650 mg Q4H PRN Maximum dosage: 4 g per 24 hours or 2 g per 24 hours in patients with comorbid liver disease First-line analgesia in noninflammatory mild OA, LBP, mild PN because of safety profile Possible adverse effects: hepatotoxicity (especially if taken with alcohol), nephrotoxicity (with chronic overdose): monitor liver and renal function when using maximal dosages Use caution and consider reducing total dosage for patients with comorbid liver disease or excessive alcohol intake NSAIDs Ibuprofen 600-800 mg TID PRN for pain Take with food Schedule around the clock for inflammatory condition (eg, inflammatory OA) or persistent symptoms Can titrate up as tolerated and based on risks to 800 mg TID Maximum dosage: 3,200 mg/day in divided doses or 1,800 mg/day for patients at increased risk of adverse effects Alternative NSAIDs Naproxen: 250-500 mg BID Sulindac: 150-200 mg BID Celecoxib: 200 mg QD Meloxicam: 7.5 mg QD For chronic pain, use for 2 weeks at initial dosage and reevaluate efficacy; titrate up as needed and if safe; if not effective after a 4-week trial, consider changing NSAID, or adding or changing to another intervention For persistent noninflammatory and inflammatory OA, LBP, mild PN Possible adverse effects: GI bleeding, abdominal pain, rash and hypersensitivity, renal and hepatic impairment, platelet aggregation abnormalities Avoid use in patients with peptic ulcer disease or cirrhosis Avoid ibuprofen in patients with history of aspirin-induced asthma Increased bleeding risk with concurrent warfarin; if used, monitor closely Increased risk of renal impairment in patients on diuretics and those with baseline renal dysfunction, congestive heart failure, or cirrhosis To minimize risks, use the lowest effective dosage and try to use for short periods of time COX-2 inhibitors, such as celecoxib, have higher risk of cardiovascular events
  • MEDICATION STANDARD DOSAGE COMMENTS but fewer GI side effects than nonselective COX inhibitors Indomethacin is associated with increased joint destruction; avoid using for OA or LBP Antidepressants: TCAs and others Amitriptyline Start at 10-25 mg QHS; titrate upward every 3 days by 25 mg to achieve symptom relief, if tolerated; maximum daily dosage is 150 mg (use lower dosages for older patients) Nortriptyline Start at 10-25 mg QHS; titrate upward every 3 days by 25 mg to achieve symptom relief, if tolerated; maximum daily dosage is 150 mg (use lower dosages for older patients) Consider for patients with comorbid depression Consider for neuropathic pain; also as an adjunct in any type of LBP unresponsive to acetaminophen and NSAIDs Small studies of PN have shown limited or negative results with antidepressants Drug interactions: RTV and other PIs may increase the level of TCAs; start at low dosage, increase slowly Monitor serum TCA levels to avoid cardiotoxicity at higher dosage levels Possible TCA adverse effects: anticholinergic (dry mouth, dizziness, constipation, urinary retention, blurred vision, orthostatic hypotension), extrapyramidal symptoms, incoordination; risk of cardiac conduction abnormalities and overdose at higher dosages For neuropathic pain, other potential agents include venlafaxine and duloxetine; these are inadequately studied in people with HIV infection or show limited efficacy Anticonvulsants Gabapentin: start at 300 mg QHS; may increase every few days, as tolerated, to achieve symptom relief; first increase to BID, then TID, then Consider for PN Gabapentin: considered first-line for HIV- SN (SeePeripheral Neuropathy) Common adverse effects include nausea, constipation, fatigue,
  • MEDICATION STANDARD DOSAGE COMMENTS increase by 300 mg per dose to maximum of 1,200 mg TID Pregabalin: start at 25-50 mg TID; may increase by 25-50 mg per dose every few days as tolerated to achieve symptom relief; maximum dosage: 200 mg TID Lamotrigine: start at 25 mg every other day; titrate slowly to 200 mg BID over the course of 6-8 weeks somnolence, dizziness, truncal ataxia, weight gain To discontinue, taper over course of ≥7 days Pregabalin: sometimes better tolerated than gabapentin Uncertain efficacy in HIV-related PN Possible adverse effects include somnolence, constipation, dizziness, ataxia, and weight gain To discontinue, taper over course of ≥7 days Lamotrigine: has shown the greatest efficacy in clinical trials for HIV-SN Possible adverse effects: rash (including Stevens-Johnson syndrome), cytopenias, dizziness To discontinue, taper slowly Drug interactions: LPV/r may decrease lamotrigine levels; may need to increase lamotrigine dosage for therapeutic effect Muscle relaxants (nonbenzo- diazepines) Cyclobenzaprine (Flexeril) 5-10 mg TID; start with 5 mg doses for elderly patients and those with hepatic impairment; maximum dosage is 30 mg per 24 hours Baclofen 5-10 mg TID or QID; start with 5 mg doses for elderly patients and those with renal impairment; maximum dosage is 80 mg QD in divided doses May be useful as adjunctive therapy for acute back pain but not recommended for chronic or subacute back pain Common adverse effects include drowsiness, dry mouth, and dizziness Severe adverse effects include arrhythmias, altered mental status, and seizures Opiate analgesics Options include: Tramadol (not a typical opiate; exact mechanism of action is unknown; acts in part as a central opioid agonist) Start with 50 mg QAM PRN pain, titrate upward by 50 mg/day every 3 days to 50 mg Q6H Maximum dosage: 400 mg/day, or 300 mg/day if >70 years of age; to Use opioids for patients who have severe pain refractory to other interventions (pharmacologic or nonpharmacologic) or who cannot receive those interventions
  • MEDICATION STANDARD DOSAGE COMMENTS discontinue, taper dosage in the same way In renal insufficiency with CrCl <30, reduce dose frequency to Q12H, and maximum dosage to 200 mg/day Weak opioids Codeine 15-30 mg every 4-6 hours; titrate up by 15 mg every 2-3 days to achieve pain relief, if tolerated Maximum dose: 60 mg; take with food Hydrocodone + acetaminophen 5 mg/500 mg fixed-dose tablet, 1-2 tablets Q6H PRN pain Maximum dosage: 12 tablets per 24 hours; 6 tablets for elderly patients and those with liver disease Oxycodone + acetaminophen 5 mg/325 mg fixed-dose tablet (other dosages available), 1-2 tablets Q6H PRN pain Maximum dosage: 12 tablets per 24 hours; 6 tablets for elderly patients and those with liver disease Strong opioids Morphine (immediate release) 10-30 mg every 3-4 hours PRN pain Morphine (sustained release) 15-30 mg Q12H as scheduled Start with weak opioids, assess safety, efficacy, and usage; titrate up and move to stronger opioids as needed Use the lowest effective dosage Use opioids cautiously in elderly patients If needed for acute flares, try to limit use to a designated short period of time If needed for chronic pain, try to use a sustained-release opioid (eg, sustained- release morphine) around the clock, plus shorteracting opioids (eg, hydrocodone) for breakthrough pain as needed Opioid therapy for chronic pain should use a fixed-dose schedule, not PRN dosing Methadone may have utility for neuropathic pain owing to its action on NMDA receptors; start at low dosage and titrate slowly because of its long half-life; consult with pharmacist Risk of dependence, overdose (accidental or deliberate); monitor closely Adverse effects include oversedation, hypotension and respiratory depression, central nervous system stimulation or somnolence, dizziness, constipation, nausea, pruritus Codeine and morphine can cause urticarial reactions (hives) For patients with renal and hepatic impairment, use low dosages and monitor carefully When prescribing opioids, remember to also give treatment for constipation (docusate and senna)
  • MEDICATION STANDARD DOSAGE COMMENTS doses; if pain control is inadequate, consider dosing Q8H; may titrate up by 15-30 mg PRN pain Oxycodone (immediate release) 5-30 mg Q4H PRN pain Oxycodone (sustained release) 10 mg Q12H as scheduled doses; titrate up by 10-20 mg PRN; monitor carefully Methadone Consult with pharmacist Hydromorphone 2-4 mg Q4H PRN Fentanyl transdermal 12-100 mcg patch Q72H; a small proportion of patients will need dosing Q48H to maintain a stable blood level Appropriate only for patients already on stable dosage of other opiates; start at equianalgesic (or lower) dosage; consult with pharmacist; use for chronic severe pain Note that tramadol 37.5 mg + acetaminophen 325 mg has shown pain relief equivalent to codeine 30 mg + acetaminophen 325 mg but with fewer adverse effects (major adverse effect: headache) Chronic opioid therapy should incorporate an opioid use agreement that includes functional goals for outcome, not reduction of pain intensity alone