Acute Pain Management in Patients With Opioid Tolerance

Adebola Adesoye, PharmD, BCPS; Nakia Duncan, PharmD, BCGP, BCPS

US Pharmacist. 2017;42(3):28-33.

Conclusion

Acute pain management presents a challenge in patients with opioid tolerance, and undertreatment is a risk in this population. Acute pain should be managed multi-modally and with effective coordination of the multi-disciplinary team to best meet the patient's analgesic needs. Patients receiving long-term OAT with methadone or buprenorphine should continue to receive maintenance therapy and may require additional treatment via a multimodal approach, including short-acting opioids, for acute pain management.

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Table 1. Multimodal Analgesia for Acute Pain Management
Drug Class	Drugs	Clinical Considerations
NSAIDs	Ibuprofen, naproxen, diclofenac, meloxicam, sulindac	Antiplatelet effects. GI bleeding risk; consider PPI use. CV risk; renal and hepatic considerations. Interactions with lithium. Available in topical, oral, and parenteral formulations
Acetaminophen		Maximum-dose considerations. Analgesic ceiling effects. Hepatic considerations. Available in oral and parenteral formulations
Opioids	Morphine, hydromorphone, oxycodone, hydrocodone, fentanyl, methadone	May be given as long-acting or short-acting formulation. Side effects and withdrawal symptoms. Assess renal and hepatic function. Available in topical, oral, and parenteral formulations
Mixed-acting analgesics	Tramadol, tapentadol	Low affinity for opioid receptors. Analgesic ceiling effect. Risk of lowering seizure threshold. May be considered adjuvant for neuropathic pain
NMDA receptor antagonists	Ketamine, methadone	May inhibit opioid tolerance. May be considered as adjuvant in opioid-tolerant patients. Ketamine shown to enhance morphine analgesic effects. Methadone administered as adjuvant to prevent opioid withdrawal
Anticonvulsants	Carbamazepine, gabapentin, pregabalin	Slow onset of pain relief. Gabapentin and pregabalin useful for neuropathic symptoms. Utility in opioid-tolerant patients not well established
Antidepressants	Venlafaxine, duloxetine, milnacipran, nortriptyline, amitriptyline	Greater evidence with neuropathic pain. Risk of serotonin syndrome with SNRIs. Risk of unpleasant side effects. Renal and hepatic considerations
Alpha₂ agonists	Dexmedetomidine, clonidine	Helps suppress opioid-withdrawal symptoms. Considered opioid-sparing and antihyperalgesic. Potentiates systemic analgesics
Corticosteroids	Dexamethasone	Possible analgesic adjuvant in opioid tolerance. Place in therapy unclear

CV: cardiovascular; GI: gastrointestinal; NMDA: N-methyl-D-aspartate; NSAID: nonsteroidal anti-inflammatory drug; PPI: proton pump inhibitor; SNRI: serotonin-norepinephrine reuptake inhibitor. Source: References 4, 5, 7, 8, 28–30, 32.

Table 2. Acute Pain Management Considerations in Older Adults
Drug Class	Considerations
Acetaminophen	Consider initial treatment for mild pain. Maximum: 3 g/day from all sources
NSAIDs	Several safety warnings exist for NSAIDs (GI bleeding, kidney disease, HF, CAD). Advise against using NSAIDs systemically. Consider topical NSAID if pain localized, unless safer therapies have failed
Opioids	Assess for renal or hepatic impairment and select opioid accordingly. Frequently evaluate pain and adverse effects. Frequently assess for therapeutic goal, and plan to titrate off once goals are achieved. Patient should have a stool softener and laxative available to prevent OIC
Adjuvants	Enhance analgesic effect of other medications. Avoid TCAs because of profound anticholinergic effects

CAD: coronary artery disease; GI: gastrointestinal; HF: heart failure; NSAID: nonsteroidal anti-inflammatory drug; OIC: opioid-induced constipation; TCA: tricyclic antidepressant.
Source: References 21, 24.

Table 3. Abuse-Deterrent Opioids
Brand Name	Generic Name	Abuse-Deterrent Mechanism
Arymo ER	Morphine	Crush/extraction-resistant
Embeda ER	Morphine-naltrexone	Agonist-antagonist
Hysingla ER	Hydrocodone	Crush/extraction-resistant
Morphabond	Morphine	Crush/extraction-resistant
Opana ER	Oxymorphone HCl	Crush/extraction-resistant
Oxaydo	Oxycodone	Crush/extraction-resistant
Targiniq ER	Oxycodone-naloxone	Agonist-antagonist
Troxyca ER	Oxycodone-naltrexone	Agonist-antagonist
Vantrela ER	Hydrocodone	Crush/extraction-resistant
Xtampza ER	Oxydocone	Crush/extraction-resistant
Zohydro ER	Hydrocodone	Crush/extraction-resistant

ER: Extended-release; HCl: hydrochloride.
Source: Reference 27.

Table 4. Treatment Strategies for Patients in Opioid-Abuse Programs
Drugs	Planned Minor/Elective Surgery	Unplanned Trauma/Surgery
Methadone	Continue usual maintenance dose; use short-acting opioids. Consider PCA	Continue usual maintenance dose; use short-acting opioids. Consider PCA
Buprenorphine	Discontinue 24–36 h prior; use short-acting opioids during/after surgery. Daily dose may be divided every 6–8 h	Start methadone 20–40 mg to treat opioid addiction. Use short-acting opioids for pain. Naloxone must be available at bedside. Switch back to buprenorphine at discharge
Naltrexone	Discontinue 72 h prior (oral). Discontinue 30 days prior for ER IM formulation; may use oral temporarily. Wait 3–7 days after discontinuing opioid before resuming naltrexone	Give regional analgesia. Use nonopioids (NSAIDs, IV acetaminophen), benzodiazepines, ketamine, clonidine. Wait 3–7 days after discontinuing opioid before resuming naltrexone