__________________ Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition
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 over the counter. 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 [23]. The most common side effect is a mild-to-severe burning sensation at the application site. CANNABINOID PREPARATIONS 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 [24] and some evidence suggests a potential benefit for chronic pain. A 2022 study concluded that oral, synthetic cannabis products with high THC-to-CBD ratios and sublingual, extracted cannabis products with comparable THC-to-CBD ratios may be associated with short-term improvements in chronic pain. The evidence for a benefit of cannabinoids on acute pain is extremely limited and mixed. A 2020 systematic review showed that there was moderate evidence to support cannabinoids in treating chronic, noncancer pain at 2 weeks and found moderate evidence that cannabinoids can exert analgesia [25]. Cannabis preparations pose both short-term and long- term risks. Short-term effects include impaired memory, motor coordination, and judgment. Paranoid ideation and psychotic symptoms, while rare, may occur with high doses of THC. Possible long-term effects include impaired brain development in young adults, potential for habituation, and increased risk of anxiety or depression. Abrupt cessation of marijuana in long-term users may cause withdrawal symptoms such as anxiety, irritability, craving, dysphoria, and insomnia. There is an increased risk of chronic bronchitis, respiratory infections, and pneumonia with inhaled products [26]. One study showed that states legalizing medical cannabis actually experienced a 22.7% increase in opioid overdose deaths [27]. FDA-approved cannabinoids including dronabinol (Marinol) and nabilone (Cesamet) are not indicated for the treatment of pain. When recommending cannabis for patients with chronic pain, clinicians may inform patients that the analgesic properties are due to both the CBD and THC components, which act on different pain pathways [28].
KETAMINE Ketamine has been successfully used to treat such acute pain conditions as sickle cell crises, renal colic, and trauma. Recently the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists released the first joint recommendations for subanesthetic ketamine (including transdermal ketamine) for acute pain [29]. PSYCHOSTIMULANTS Psychostimulants have a higher likelihood of being misused due to their effects on the central nervous system. Psychostimulants with abuse potential include both illegal drugs (cocaine, methamphetamine, and ecstasy) and prescription stimulants. Approximately 3.9 million people aged 12 or older misused prescription stimulants in 2023 [30].
OPIOIDS
MECHANISM OF ACTION Opioids exert their analgesic effects by acting on the mu, kappa, and delta opioid receptors. Individual agents may be classified as agonists or partial agonists of those receptors: • Agonists (e.g., morphine, codeine, hydromor- phone, hydrocodone) stimulate at least one of the opioid receptors and provide continued analgesia with increasing doses. • Partial agonists (e.g., buprenorphine) have high affinity at mu-receptors, have a ceiling for analgesic effect, and are less likely to cause respiratory depression. Opioids are classified by the DEA according to their presumed
abuse and addiction potential. RELATIVE EFFECTIVENESS
The analgesic efficacy of opioids for treating acute pain has been known for centuries, and they continue to be reliable agents for moderate-to-severe acute pain, although they are not without risks. But the evidence for opioid efficacy for acute pain cannot be extended to chronic pain with a few exceptions discussed subsequently. Neuronal and physiologic adaptations to long-term opioid use can result in reduced analgesic effectiveness, or even, paradoxically, increased pain or sensitivity to pain [31]. Opioid-induced hyperalgesia is different pharmacologically from the phenomenon of opioid tolerance, although both can lead to an increased need for opioids, and disentangling the two clinically can be difficult [32].
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