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Various Adjuvant Agents Used for Pain Management
Drug/principal mechanism of actionPain indicationsCommon dosing1Common side effectsSpecial considerations
  • Tramadol
  • Dual mechanism: serotonin/norepinephrine reuptake inhibition
  • Weak mu-opioid receptor agonism
  • Acute and chronic pain: moderate–severe1
  • Postoperative pain2
  • Neuropathic pain2
50–100 mg po q6–8 h
  • Nausea, vomiting, constipation, dizziness, headaches
  • Serious reactions: seizures, serotonin syndrome
  • Caution if history/risk of seizure
  • Avoid abrupt cessation
  • Risk of suicidality
  • Pregnancy Class C
  • Clonidine
  • Central alpha-2 adrenergic agonist
  • Peripheral neuropathy2
  • Postherpetic neuralgia2
  • Cancer pain2
  • CRPS2
  • Postoperative pain2
  • Adjuvant in neuraxial and peripheral nerve blocks2
  • Opioid withdrawal2
  • 0.1 mg po q12 h weekly titration up to 2.4 mg/day
  • 0.1 mg/day transdermal
  • Up to 0.6 mg/day
  • 30 μg/h epidural infusion
Hypotension, bradycardia, AV block, dry mouth, drowsiness, sedation fatigue, depression, fever
  • Avoid abrupt withdrawal, risk of rebound hypertension
  • Pregnancy Class C
  • Ketamine
  • NMDA receptor antagonism
  • Intraoperative and postoperative pain2
  • Burn pain2
  • Cancer pain2
  • Neuropathic pain2
  • Opioid-induced hyperalgesia2
  • IV infusion
  • Transdermal
  • SQ infusion
In analgesic doses: hypersalivation, anorexia, nausea, elevated BP, hallucinations, withdrawal syndrome (long-term use)
  • Black box warnings: emergence reactions—various degrees of psychologic manifestations from pleasant dream-like states to irrational behavior and emergence delirium. The 100 mg/mL concentration of ketamine hydrochloride injection should not be injected intravenously without proper dilution
  • Pregnancy Class D
  • Blocks sodium channels
  • Decreases ionic flux through the neuronal membrane
  • Postherpetic neuralgia1
  • Local anesthesia, postoperative pain1
  • Neuropathic pain2
  • Burn pain2
  • Topical: transdermal
  • maximum three patches/ 24 h
  • IV: various protocols
Pregnancy Class C

1FDA approved.

2Off-label usage for neuropathic pain.

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Muscle Relaxant Agents Commonly Used in Pain Management
Drug/principal mechanism of actionPain indicationsCommon dosing1Common side effectsSpecial considerations
  • Baclofen
  • GABA-B agonist
  • Spasticity2
  • Myofascial pain3
  • Trigeminal neuralgia3
  • GERD3
  • Oral: start at 5 mg TID
  • Maximum 80 mg/day
  • Intrathecal: for severe spasticity
Drowsiness, weakness, fatigue, hypotension, constipation, nausea
  • Black box warnings (for the intrathecal administration): avoid abrupt cessation—high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity after abrupt D/C
  • Pregnancy Class C
  • Benzodiazepines:
  • Diazepam
  • Clonazepam
  • GABA-B agonist
  • Diazepam:
  • Muscle spasm
  • Acute postoperative myofascial pain3
  • Clonazepam:
  • Neuralgia
  • Periodic leg movement
  • Spasticity3
  • Diazepam:
  • 2–10 mg po q6–8 h
  • 5–10 mg IM/IV4
  • q3–4 h prn
  • Clonazepam:
  • 0.5–4 mg po q8 h
Drowsiness, dizziness, impaired coordination, amnesia, confusion, somnolence, irritability
  • Significant dependence, abuse and addiction potential associated with chronic benzodiazepine administration
  • Pregnancy Class D
  • Tizanidine
  • Central alpha-2 adrenergic agonist
  • Spasticity2
  • Muscle spasm and pain3
  • Acute pain3
  • Chronic headache3
2–8 mg TIDDrowsiness, dry mouth, somnolence, asthenia, hypotension, bradycardia
  • Additive effects with alcohol and other CNS depressants
  • Reduced clearance with oral contraceptives
  • Pregnancy Class C
  • Cyclobenzaprine
  • Centrally acting muscle relaxant
  • Muscle spasm and pain2
  • Fibromyalgia3
  • TMJ disorder3
5–10 mg po TID
  • Drowsiness, dry mouth, ...

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