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Updated: Apr 30 2023

Opiates & Analgesic Medications

  • Introduction
    • Definitions
      • acute pain
        • implies presence of tissue damage
      • chronic pain (3-6 months)
        • no implication of tissue damage necessary
      • pathologic pain
        • pain from abnormal nervous system functioning (neuropathic)
    • Pathophysiology
      • afferent pain pathways
        • nociceptors
          • transduce signal through various substances
            • Substance P
              • a sensory neurotransmitter that plays an important role in pain
              • depletion of substance P increases the threshold to painful stimuli
              • Capsaicin is thought to function by decreasing Substance P
        • peripheral nerves
          • nociceptors transmit pain to type A and C peripheral nerve fibers
        • spinal cord
          • peripheral nerves transmit the pain signal via the dorsal column and spinothalamic tract
        • brainstem
          • spinal cord transmits the pain signal to the thalamus
          • site of pain modulation with endogenous opiates
    • Agents (details below)
      • Acetaminophen
      • NSAIDS
      • Opiates
      • Gaba synthesis agents
      • Adjunctive agents
  • Indications & Special Consideratoins
    • Pediatric patients
      • follow specific dosing guidelines for children which have been tested and recommended by the American Academy of Pediatrics
    • Geriatric patients
      • may have increased sensitivity to opioid pain medicines with higher rates of side effects
        • decreased total body mass with increased body fat percentage
        • potentially decreased hepatic and renal function
    • Obese patients
      • achieving adequate peri-operative pain control in the morbidly obese can be difficult
      • the most accurate method to control pain and avoid respiratory depression should include patient controlled analgesia (PCA), which is based on the patient's ideal weight
      • intramuscular injections should be avoided due to the difficulty of avoiding injection into muscle and the poor vascularity of the subcutaneous adipose tissue
    • Red-haired patients
      • often require more anaesthesia to maintain MAC levels and higher opioid dosages postoperatively compared to other hair types
    • Chronic regional pain syndrome
      • Vitamin C has been shown to possibly prevent CRPS specifically related to distal radius fractures
  • Acetaminophen
    • Mechanism
      • not fully understood
      • inhibits prostaglandin synthesis
      • minimal antinflammatory effects
    • As effective for pain control as aspirin
    • Toxicity
      • overdose leads to hepatic disfunction
      • contraindicated in the setting of pre-existing hepatic dysfunction
  • NSAIDs
    • Mechanism
      • decrease transduction of pain
    • See anti-inflammatory medications
  • Local anesthetics
    • Mechanism
      • decrease transduction of pain
      • interfere with nerve conduction to provide a reversible loss of sensation in a specific location
        • affects the depolarization phase of action potentials (cells fail to depolarize enough to fire after excitation leading to a blocked action potential)
    • Examples
      • amide family
        • lidocaine (Xylocaine)
        • bupivacaine (Marcaine)
      • esters of p-aminobenzoic acid
        • procaine (Novocain)
        • butethamine (Monocaine)
      • esters of meta-aminobenzoic acid
        • cyclomethycaine (Surfacaine)
        • metabutoxycaine (Primacaine)
      • esters of benzoic acid
        • cocaine
        • ethyl aminobenzoate (Benzocaine)
    • Adverse effects
      • FDA warning on the administration of continuous intra-articular infusion of local anesthetics for pain control
        • Some patients have been noted to have chondrolysis following infusion
  • Opiates
    • Overview
      • useful in chronic nociceptive pain
    • Mechanism
      • perispinal method affects modulation of pain
      • systemic opiates change the perception and modulation of pain
    • Administration
      • oral, IV, intraspinal
      • oral administration preferred (more convenient and less costly)
        • bony procedures require more analgesia than soft tissue procedures
      • patient compliance can improve with long-acting preparations that providue more uniform serum drug levels
      • implantable systems are available for intrathecal administration
    • Prescription dosing guide for upper extremity surgery
      • no narcotics
        • trigger finger release, nonop Dupuytren's release, small lumps/bumps
      • 10 narcotic tablets
        • mucous cyst, carpal tunnel, deQuervain’s, Dupuytren’s releases and small joint fusion
      • 20 narcotic tablets
        • wrist ganglion cysts, hand fracture ORIF, LRTI and tendon transfers
      • 40 narcotic tablets
        • large trauma, wrist fusion, open carpal surgery and DRUJ reconstruction
    • Chronic use
      • addiction occurs in a minority of patients
      • chronic opiates should be prescribed by pain management specialists
      • written contracts should be obtained
      • prescriptions should always be refilled in person
      • when used for OA, increases rate of surgical complications
  • Methadone
    • Synthetic diphenylheptaine-derivative opioid receptor agonist
    • High bioavailability (three times as much as morphine), effective, and inexpensive
    • Metabolism
      • cytochrome P450 system
    • Rapid distribution phase (2-3 hours) and prolonged elimination phase (15-60 hours)
    • Caution
      • can accumulate to high levels with repeated dosing
      • rates of elimination vary considerably
      • risk of respiratory depression, cardiac toxicity (torsades de pointes)
      • consult with a qualified pain specialist when prescribing for the first-time
  • GABA agents
    • Agents
      • Pregabalin (Lyrica)
      • Gabapentin (Neurontin)
    • Mechanism
      • decrease transduction of pain
        • reduce hyper-excitability of voltage dependent Ca2+ channels in activated neurons.
    • Gabapentin is an anticonvulsant also used to treat neuropathic pain
      • binds presynaptic calcium channels to inhibit release of neurotransmitters
    • Efficacy
      • evidence of effectiveness primarily for postherpetic neuralgia, diabetic nueropathy, and fibromyalgia
      • little evidence for other uses, though often prescribed for other forms of chronic neuropathic pain (such as complex regional pain syndrome, CRPS)
      • gabapentin has been shown to be as effective and less expensive than pregabalin
    • Discontinuation requires a tapering dose
  • Muscle relaxants
    • Overview
      • Useful to treat pain secondary to muscle spasms
    • Agents
      • Cyclobenzaprine (Flexeril)
        • mechnism of action not fully understood
        • centrally acting
        • potentiates norepinephrine and binds serotonin receptors
    • Use
      • may decrease pain during first two weeks after an injury
      • no proven benefit after first two weeks
      • may be effective for fibromyalgia
      • not effective to reduce spasticity secondary to neuromuscular disorders
    • Toxicity
      • overdose rare
      • may interact with other substances
        • MAOIs
        • alcohol
  • Adjuvant agents
    • Heterogeneous class of medications the provide additive analgesic effect to traditional NSAIDs and opioids
      • anticonvulsants
      • antidepressants
      • antihistamines
      • psychostimulants
      • anti-spasmodics
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