Non-opioid drug approaches A wide range of medications can be used to treat pain, including: ● Acetaminophen ● NSAIDs (oral or topical) ● Antidepressants ● serotonin and/or norepinephrine reuptake inhibitors ● tricyclic antidepressants (TCAs) ● selective serotonin reuptake inhibitors (SSRIs) ● Anticonvulsants Lower doses of acetaminophen are recommended to decrease risk of side effects. Patients should not exceed 1000 mg in a single dose. The maximum recommended dose for healthy adults is 4000 mg/ day. 47 . 47 The most severe potential side effect of acetaminophen is liver toxicity. Acetaminophen is the most common cause of acute liver failure, accounting for 46% of all cases. 48 Patients should stay within recommended doses to help prevent side effects and should only be prescribed one acetaminophen- containing product at a time. NSAIDs Chronic use of NSAIDs may be limited by gastrointestinal (GI) toxicity, including GI bleeding, upper GI symptoms, ulcers, and related complications. For high-risk patients, including the elderly, patients on warfarin or aspirin, and those with coagulopathies, adding a proton pump inhibitor (PPI) may help reduce the risk. 49,50 In addition to GI side effects, NSAIDs have been associated with an increased risk of renal and cardiac complications. Side effects with NSAIDs are typically lower with topical formulations. ● Topical lidocaine or capsaicin ● Cannabinoid-based therapies ● Ketamine Acetaminophen Some early trials suggested that COX-2 inhibitors, as a class, were associated with higher risks for myocardial infarction and stroke compared to other NSAIDs, and the COX-2 inhibitor rofecoxib (Vioxx) was removed from the market in 2004 because of such concerns. 51 More recent trials and meta-analyses, however, provide strong evidence that the risks of CV events with celcoxib are no greater than those of other NSAIDs, and in 2018 two FDA advisory panels recommended that the FDA change its advice to physicians regarding celecoxib’s safety. 52 Selective serotonin norepinephrine reuptake inhibitors SNRIs such as duloxetine, venlafaxine, and milnacipran are characterized by a mixed action on norepinephrine and serotonin, though their exact mechanism of action for pain reduction is unknown. These agents affect the descending pain pathways to facilitate pain relief. Side effects (e.g., nausea, dizziness, and somnolence) may limit treatment. Monitoring is suggested for blood pressure (duloxetine and venlafaxine), heart rate (venlafaxine), and drug interactions (duloxetine).
SNRIs can be very helpful in patients who have central sensitization. TCAs TCAs inhibit reuptake of norepinephrine and serotonin. These agents act on descending pain pathways, but their mechanism of action for pain relief is unknown. Examples of TCAs studied for the management of chronic pain include amitriptyline, desipramine, and nortriptyline. Side effects, such as anticholinergic effects (e.g., dry mouth, constipation, dizziness) and QTc prolongation limit the use of TCAs in elderly patients. The majority of side effects occur at the typically higher doses used to treat depression. SSRIs SSRIs, such as citalopram, fluoxetine, and paroxetine, block the reuptake of serotonin in the brain, making more serotonin available in the synapse. The mechanism of SSRIs for pain remains unknown. Compared to SNRIs and TCAs, there is relatively little evidence to support the use of SSRIs in treating chronic pain conditions. 28 Potential side effects of SSRIs include weight gain, sexual dysfunction, and QTc prolongation, especially with citalopram. Anticonvulsants Anticonvulsants, such as gabapentin, pregabalin, oxcarbazepine, and carbamazepine, are often prescribed for neuropathic pain and are thought to exert their analgesic effect by inhibiting neuronal calcium channels. Potential side effects include sedation, dizziness, and peripheral edema. Pregabalin and gabapentin have low abuse potential in the general population, are currently classified as Schedule V by the DEA, and prescriptions for these drugs are tracked by some state Prescription Drug Monitoring Programs (PDMPs). Anticonvulsants can be very helpful in patients who have central sensitization and neuropathic pain. Topical lidocaine and capsaicin Topical lidocaine inhibits the conduction of nociceptive nerve impulses. Irritation at the application site is the most common side effect. The most common products for chronic pain management are lidocaine 5% patches, available by prescription, and lidocaine 4% patches available OTC. Capsaicin is an active component of chili peppers and has moderate analgesic properties at 8% concentrations for neuropathic pain, specifically postherpetic neuralgia and diabetic neuropathic pain of the feet. 53 The most common side effect is a mild-to-severe burning sensation at the application site. Cannabinoid preparations With medical cannabis now legal in 38 states and recreational use legal in at least 24 states and the District of Columbia (as of 2023), there has been increased interest among patients for the use of cannabis or cannabis derivatives (e.g., cannabidiol [CBD]) for pain relief. The CB1 and CB2 receptors have been shown to mediate the analgesic effects of cannabinoids 55 and some evidence suggests a potential benefit for chronic pain.
Book Code: MDAZ1124
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