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Chronic Pain - Coggle Diagram
Chronic Pain
Non-pharmacologic Treatment
Exercise
Physical therapy
Diet
Electroanalgesia (application of electrical stimulation to various areas that range from noninvasive to highly invasive)
Noninvasive: transcutaneous electrical nerve stimulation (TENS)
Minimally invasive: percutaneous electrical nerve stimulation (PENS)
Highly invasive: spinal cord stimulation (SCS)
Weight loss
CBT, relaxation, meditation, Tai chi
Pharmacologic Treatment
Opioids
Phenathrenes (morphine-like agonists)
Morphine, hydromorphone, oxymorphone, codeine
MOA: inhibits ascending pain pathways by binding to opioid receptors in the CNS; generalized CNS depression
PK/PD: fast onset of action (PO 30 mins, IV 5-10 mins); hepatic metabolism (morphine to active metabolite M6G, codeine via CYP2D6 and CYP3A4, others to inactive metabolites)
BBW: ethanol use; high risk of addiction, abuse, and misuse; REMS; respiratory depression; neonatal opioid withdrawal syndrome
Special populations: avoid use in pregnancy; not safe in breastfeeding
Phenylpiperidines (meperidine-like agonists)
Meperidine, fentanyl
MOA: binds at many sites in the CNS; inhibits ascending pain pathways
BBW: respiratory depression; high risk of addiction, abuse, and misuse; REMS; CYP3A4 interaction
PK/PD: fast onset of action; high protein binding; CYP3A4 metabolism
DDI: BZDs; CYP3A4 substrates
Special populations: do not use in pregnancy; avoid use in breastfeeding
MOA: Act as agonists of the mu/kappa/delta opioid receptors; activation of CNS pathway to inhibit nociceptive pain signaling
BBW: Potential for fatal respiratory depression may occur
BBW: High risk of addiction, abuse, and misuse
DDI: barbiturates, carbamazepine, phenytoin, rifampin, SSRIs, PPIs, fluoroquinolones, azole antifungals, other opioid analgesics, MAOIs, anticholinergic medications, gabapentin, lithium
Patients should also avoid grapefruit juice and alcohol while taking any opioid analgesics
Diphenylheptanes (methadone-like agonists)
Methadone, tramadol
MOA: inhibits ascending paint pathways by binding to opiate receptors in the CNS
PK/PD: high protein binding; CYP metabolism (3A4, 2B6, 2C19, 2C9, 2D6)
BBW: high risk of addition, abuse, and misuse; REMS; respiratory depression; QT prolongation; use with CYP450 inhibitors
DDI: CYP450 inducers; other QT-prolonging agents; grapefruit juice
Special populations: can be used in mothers w/ opioid use disorder, otherwise avoid in pregnancy; safe in breastfeeding
Monitoring: signs of respiratory depression; signs of hypotension or heart rate changes; continually reassess the maintenance of pain control and need for continued opioid therapy; monitor for addiction
Harm reduction strategies: clinicians should start with the lowest effective dose; continual follow-up with patients on opioid therapy to assess risk of addiction and pain management; offering naloxone to patients on opioid therapy; avoid concurrent use of benzodiazepines; use ORT or DAST-10 to screen patients for risk of opioid use disorder; patients can also be screened with urine drug tests during therapy to monitor for increased use
Counseling points
Patients should avoid activities requiring mental alertness or coordination until drug effects are realized
Side effects include: n/v, insomnia, hyperhidrosis, fatigue, chills, anorexia, and headache
Patient should be initiated on constipation therapy
Patient should not abruptly discontinue opioid therapy as withdrawal symptoms may occur
Withdrawal signs: flu-like symptoms, fatigue, muscle aches, increased HR, shakiness, anxiety
Skeletal muscle relaxants
Baclofen
MOA: inhibits transmission of monosynaptic and polysynaptic reflexes at the spin cord level (possibly by hyperpolarization of primary afferent fiber terminals), causing relief of muscle spasticity
PK/PD: 30% protein binding; primarily excreted as unchanged drug
ADRs: confusion; dizziness; drowsiness; sedation; asthenia; N/V
DDI: other CNS depressants; anticholinergic agents
BBW: abrupt withdrawal (injection)
Special populations: if use in pregnancy, use intrathecal baclofen instead of oral; present in breast milk
Cyclobenzaprine
MOA: related to TCAs; reduces tonic somatic motor activity, influencing both alpha and gamma motor neurons
PK/PD: onset of action within 1 hour; CYP3A4, 1A2, and 2D6 metabolism
ADRs: drowsiness; dizziness
DDI: other CNS depressants; anticholinergic agents
Special populations: decrease dose in hepatic impairment and the elderly; little info about safety in pregnancy; safe in breastfeeding
Anticonvulsants
Gabapentinoids
Pregabalin
MOA: same as gabapentin
DPN, fibromyalgia, neuropathic pain associated with spinal cord injury, PHN, perioperative pain
Gabapentin
MOA: inhibition of the voltage-gated Ca2+ channel leading to decrease of excitatory NT including glutamate, NE, substance +
PHN, restless leg syndrome, neuropathic pain, perioperative pain,
requires renal dose adjustment
risk for misuse/abuse
Carbamazepine
MOA: inhibits voltage-gated Na+ channels, potentiates GABA
used in trigeminal neuralgia and neuropathic pain
significant DDIS
test for HLA-B1-1502 allele in asian patients due to lethal rash
monitor CBC, LFTs, Sodium level - no correlation between analgesia and serum drug concentration
Oxcarbazepine
MOA: inhibits Na+ channels
used for Trigeminal neuralgia & neuropathic pain
improved tolerability and less DDI compared to CBZ
Lamotrigine
MOA: inhibits Na+ Channels
neuropathic pain (4th line in canadian guidelines)
Stevens-Johnson Syndrome
Topiramate
MOA: Inhibits voltage-gated Na+ channels, AMP/Kainite subtype of glutamate receptor, and carbonic anhydrase; increases activity of GABA-A Receptor
Alcohol Use disorder - migraine ppx - neuropathic pain (4th line in Canadian NP guidelines)
Monitor serum bicarbonate and renal function, increased risk for kidney stones, weight loss, decreased sweating/hyperthermia, hyperammonemia
Nonopioid analgesics
Preferred first-line therapies in treatment of mild-to-moderate pain
ADE: GI upsets, dizziness
Avoid in renal disease and ulcer disease
Acetaminophen
325-600 mg PO q4-6h PRN or 1 g q6h PRN
maximum dose: 4g/day
PK/PD:
onset of action <1hr
duration 4-6 hrs
primarily absorbed in small intestine
at normal therapeutic dosages
primarily hepatic metabolism
the half-life may increase 2-fold or more in patients with liver disease
MOA: although not fully elucidated, the analgesic effects are believed to be due to activation of descending serotonergic inhibitory pathways in the CNS
NSAIDs
BBW:
use of NSAIDs around 20 weeks' gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment, which may be fatal
BBW:
serious gastrointestinal bleeding, ulcerations, and perforation
BBW:
Serious gastrointestinal bleeding, ulcerations, and perforation
MOA: reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties
Aspirin
325 mg to 1 g PO every 4 to 6 hrs PRN
maximum dose: 4g/day
Ibuprofen
200 to 400 mg PO every 4 to 6 hrs PRN
or
600 to 800 mg PO every 6 to 8 hrs PRN
maximum dose: 3.2 g/day
Celecoxib
Initial 400 followed by another 200 on first day, then 200 twice daily
Diclofenac
Oral
IR tablet: 50 mg 2 to 3 times daily
Delayed-release tablet: 50 mg 2 to 3 times daily or 75 mg twice daily
Extended-release tablet: 100 mg once daily
IR capsule: 35 mg 3 times daily
Topical
Patch: apply 1 patch twice daily to most painful area
Gel:
1.16%: Apply 2 g to 4 g to the skin over affected area(s) 3 or 4 times daily for up to 7 days
2.32%: Apply 2 g to the skin over affected area(s) twice daily for up to 7 days (maximum: 4 g/24 hours)
Ketorolac
Oral
10 mg q 4-6h (max 40 mg/day)
Injection
307–60 (single IM dose only)
157–30 (single IV dose only)
107–30 every 6 h (IV dose) (max. 5 days)
Antidepressants
SNRIs
MOA: inhibits reuptake of serotonin and NE which inhibits the descending pain pathway
Indication: chronic musculoskeletal pain, diabetic neuropathy, fibromyalgia, CINP
Duloxetine
Dose: initial 30 mg PO daily x 1 week, target 60 mg/day; MAX 120 mg/day
Avoid CrCl <30; in chronic liver disease or cirrhosis
Venlafaxine: associated with QTc prolongation
Dose: Initial 37.5 mg PO daily, titrate by 75 mg/d q4 days, MAX 225 mg/day
Adjust for renal/hepatic impairment
ADE: nausea, somnolence, anorexia, sexual dysfunction, and constipation, hypertension, bleeding
TCAs
Amitriptyline: tertiary amine (more ADE)
MOA: Inhibits reuptake of serotonin and norepinephrine which inhibits the descending pain pathway
Nortriptyline
Secondary amine (fewer ADE with similar efficacy)
Indication: fibromyalgia, low back pain, migraine prophylaxis, neuropathic pain
ADE: QTc prolongation, arrhythmias, tachycardia, orthostatic hypotension, anticholinergic effects, sedation, lower seizure threshold
Dosing: Start 10-25 mg PO QHS; titrate by 10-25 mg q3-7 days
MAX 150 mg (doses >100 mg associated with sudden cardiac death)
Clinical Presentation
Symptoms: sharp, dull, shock-like, tingling, shooting, radiating, fluctuating in intensity, and varying in location
General: patients may not show suffering so providers should look for mental/emotional signs including anxiety, depression, fatigue, anger, and fear
HTN, tachycardia, diaphoresis, mydriasis, and pallor may be present
Pathophysiology
Nociceptive (Adaptive) Pain: (1) nociceptors activated by mechanical, thermal, and chemical stimuli. (2) chemical signal converted to electrical signal by voltage-gated Na channels and transmitted by A-delta and C fibers. (3) pain fibers synapse in the dorsal horn of spinal cord where signal is converted back to chemical neurotransmitters. (4) In the brain, pain is either amplified by glutamate and substance P or attenuated by GABA, opioids, 5-HT.
Pathologic (Maladaptive) Pain
Neuropathic: peripheral or CNS nerve injury (caused by chemotherapy, surgery, stroke, etc) causes chronic pain response
Centralized: no nerve injury exists, but there is disturbance in pain processing causing hypersensitivity to stimuli
Treatment Goals
Achieve a level of pain relief that allows the patient to attain functional goals such as participating in physical therapy, reducing medication use, allowing for freedom of movement, tolerating ADLs, and minimizing adverse effects